A vaccine is a biological
preparation
Preparation may refer to:
* Preparation (dental), the method by which a tooth is prepared when removing decay and designing a form that will provide adequate retention for a dental restoration
* Preparation (music), treatment of dissonance in tona ...
that provides active
acquired immunity
The adaptive immune system, also known as the acquired immune system, is a subsystem of the immune system that is composed of specialized, systemic cells and processes that eliminate pathogens or prevent their growth. The acquired immune system ...
to a particular
infectious
An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dise ...
or
malignant
Malignancy () is the tendency of a medical condition to become progressively worse.
Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not s ...
disease.
The safety and effectiveness of vaccines has been widely studied and verified.
A vaccine typically contains an agent that resembles a disease-causing microorganism and is often made from weakened or
killed forms of the microbe, its toxins, or one of its surface proteins. The agent stimulates the body's
immune system
The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
to recognize the agent as a threat, destroy it, and to further recognize and destroy any of the microorganisms associated with that agent that it may encounter in the future.
Vaccines can be
prophylactic
Preventive healthcare, or prophylaxis, consists of measures taken for the purposes of disease prevention.Hugh R. Leavell and E. Gurney Clark as "the science and art of preventing disease, prolonging life, and promoting physical and mental hea ...
(to prevent or ameliorate the effects of a future
infection
An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dise ...
by a natural or "wild"
pathogen
In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ ...
), or
therapeutic
A therapy or medical treatment (often abbreviated tx, Tx, or Tx) is the attempted remediation of a health problem, usually following a medical diagnosis.
As a rule, each therapy has indications and contraindications. There are many different ...
(to fight a disease that has already occurred, such as
cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
).
Some vaccines offer full
sterilizing immunity
A neutralizing antibody (NAb) is an antibody that defends a cell from a pathogen or infectious particle by neutralizing any effect it has biologically. Neutralization renders the particle no longer infectious or pathogenic.
Neutralizing antibod ...
, in which infection is prevented completely.
The administration of vaccines is called
vaccination
Vaccination is the administration of a vaccine to help the immune system develop immunity from a disease. Vaccines contain a microorganism or virus in a weakened, live or killed state, or proteins or toxins from the organism. In stimulating ...
. Vaccination is the most effective method of preventing infectious diseases; widespread immunity due to vaccination is largely responsible for the
worldwide eradication of
smallpox
Smallpox was an infectious disease caused by variola virus (often called smallpox virus) which belongs to the genus Orthopoxvirus. The last naturally occurring case was diagnosed in October 1977, and the World Health Organization (WHO) c ...
and the restriction of diseases such as
polio
Poliomyelitis, commonly shortened to polio, is an infectious disease caused by the poliovirus. Approximately 70% of cases are asymptomatic; mild symptoms which can occur include sore throat and fever; in a proportion of cases more severe s ...
,
measles
Measles is a highly contagious infectious disease caused by measles virus. Symptoms usually develop 10–12 days after exposure to an infected person and last 7–10 days. Initial symptoms typically include fever, often greater than , cough, ...
, and
tetanus
Tetanus, also known as lockjaw, is a bacterial infection caused by ''Clostridium tetani'', and is characterized by muscle spasms. In the most common type, the spasms begin in the jaw and then progress to the rest of the body. Each spasm usually ...
from much of the world. The
World Health Organization
The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...
(WHO) reports that licensed vaccines are currently available for twenty-five different
preventable infections.
The folk practice of
inoculation
Inoculation is the act of implanting a pathogen or other microorganism. It may refer to methods of artificially inducing immunity against various infectious diseases, or it may be used to describe the spreading of disease, as in "self-inoculati ...
against
smallpox
Smallpox was an infectious disease caused by variola virus (often called smallpox virus) which belongs to the genus Orthopoxvirus. The last naturally occurring case was diagnosed in October 1977, and the World Health Organization (WHO) c ...
was brought from
Turkey
Turkey ( tr, Türkiye ), officially the Republic of Türkiye ( tr, Türkiye Cumhuriyeti, links=no ), is a list of transcontinental countries, transcontinental country located mainly on the Anatolia, Anatolian Peninsula in Western Asia, with ...
to Britain in 1721 by
Lady Mary Wortley Montagu
Lady Mary Wortley Montagu (née Pierrepont; 15 May 168921 August 1762) was an English aristocrat, writer, and poet. Born in 1689, Lady Mary spent her early life in England. In 1712, Lady Mary married Edward Wortley Montagu, who later served a ...
.
The terms ''vaccine'' and ''vaccination'' are derived from ''Variolae vaccinae'' (smallpox of the cow), the term devised by
Edward Jenner
Edward Jenner, (17 May 1749 – 26 January 1823) was a British physician and scientist who pioneered the concept of vaccines, and created the smallpox vaccine, the world's first vaccine. The terms ''vaccine'' and ''vaccination'' are derived f ...
(who both developed the concept of vaccines and created the first vaccine) to denote
cowpox
Cowpox is an infectious disease caused by the ''cowpox virus'' (CPXV). It presents with large blisters in the skin, a fever and swollen glands, historically typically following contact with an infected cow, though in the last several decades more ...
. He used the phrase in 1798 for the long title of his ''Inquiry into the Variolae vaccinae Known as the Cow Pox'', in which he described the protective effect of cowpox against smallpox.
In 1881, to honor Jenner,
Louis Pasteur
Louis Pasteur (, ; 27 December 1822 – 28 September 1895) was a French chemist and microbiologist renowned for his discoveries of the principles of vaccination, microbial fermentation and pasteurization, the latter of which was named afte ...
proposed that the terms should be extended to cover the new protective inoculations then being developed.
The science of vaccine development and production is termed ''
vaccinology
A vaccine is a biological Dosage form, preparation that provides active acquired immunity to a particular infectious disease, infectious or cancer, malignant disease. The safety and effectiveness of vaccines has been widely studied and verifie ...
''.
Effects
![RougeoleDP](https://upload.wikimedia.org/wikipedia/commons/2/27/RougeoleDP.jpg)
There is overwhelming scientific consensus that vaccines are a very safe and effective way to fight and eradicate infectious diseases. The
immune system
The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
recognizes vaccine agents as foreign, destroys them, and "remembers" them. When the
virulent
Virulence is a pathogen's or microorganism's ability to cause damage to a host.
In most, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host. The pathogenicity of an organism—its ability to ca ...
version of an agent is encountered, the body recognizes the protein coat on the virus, and thus is prepared to respond, by first neutralizing the target agent before it can enter cells, and secondly by recognizing and destroying infected cells before that agent can multiply to vast numbers.
Limitations to their effectiveness, nevertheless, exist.
Sometimes, protection fails for vaccine-related reasons such as failures in vaccine attenuation, vaccination regimens or administration.
Failure may also occur for host-related reasons if the host's immune system does not respond adequately or at all. Host-related lack of response occurs in an estimated 2-10% of individuals, due to factors including genetics, immune status, age, health and nutritional status.
One type of
primary immunodeficiency
Primary immunodeficiencies are disorders in which part of the body's immune system is missing or does not function normally. To be considered a ''primary'' immunodeficiency (PID), the cause of the immune deficiency must not be secondary in nature ...
disorder resulting in genetic failure is
X-linked agammaglobulinemia
X-linked agammaglobulinemia (XLA) is a rare genetic disorder discovered in 1952 that affects the body's ability to fight infection. As the form of agammaglobulinemia that is X-linked, it is much more common in males. In people with XLA, the lymphop ...
, in which the absence of an enzyme essential for
B cell
B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or ...
development prevents the host's immune system from generating
antibodies
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
to a
pathogen
In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ ...
.
Host–pathogen interactions and responses to infection are dynamic processes involving multiple pathways in the immune system.
A host does not develop antibodies instantaneously: while the body's
innate immunity
The innate, or nonspecific, immune system is one of the two main immunity strategies (the other being the adaptive immune system) in vertebrates. The innate immune system is an older evolutionary defense strategy, relatively speaking, and is the ...
may be activated in as little as twelve hours,
adaptive immunity
The adaptive immune system, also known as the acquired immune system, is a subsystem of the immune system that is composed of specialized, systemic cells and processes that eliminate pathogens or prevent their growth. The acquired immune system ...
can take 1–2 weeks to fully develop. During that time, the host can still become infected.
Once antibodies are produced, they may promote immunity in any of several ways, depending on the class of antibodies involved. Their success in clearing or inactivating a pathogen will depend on the amount of antibodies produced and on the extent to which those antibodies are effective at countering the strain of the pathogen involved, since different strains may be differently susceptible to a given immune reaction.
In some cases vaccines may result in partial immune protection (in which immunity is less than 100% effective but still reduces risk of infection) or in temporary immune protection (in which immunity wanes over time) rather than full or permanent immunity. They can still raise the reinfection threshold for the population as a whole and make a substantial impact.
They can also mitigate the severity of infection, resulting in a lower
mortality rate
Mortality rate, or death rate, is a measure of the number of deaths (in general, or due to a specific cause) in a particular population, scaled to the size of that population, per unit of time. Mortality rate is typically expressed in units of de ...
, lower
morbidity
A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not immediately due to any external injury. Diseases are often known to be medical conditions that a ...
, faster recovery from illness, and a wide range of other effects.
Those who are older often display less of a response than those who are younger, a pattern known as
Immunosenescence
Immunosenescence is the gradual deterioration of the immune system, brought on by natural age advancement. A 2020 review concluded that the adaptive immune system is affected more than the innate immune system. Immunosenescence involves both the h ...
.
Adjuvants In pharmacology, an adjuvant is a drug or other substance, or a combination of substances, that is used to increase the efficacy or potency of certain drugs. Specifically, the term can refer to:
* Adjuvant therapy in cancer management
* Analgesi ...
commonly are used to boost immune response, particularly for older people whose immune response to a simple vaccine may have weakened.
The
efficacy
Efficacy is the ability to perform a task to a satisfactory or expected degree. The word comes from the same roots as ''effectiveness'', and it has often been used synonymously, although in pharmacology a pragmatic clinical trial#Efficacy versu ...
or performance of the vaccine is dependent on several factors:
* the disease itself (for some diseases vaccination performs better than for others)
* the strain of vaccine (some vaccines are specific to, or at least most effective against, particular strains of the disease)
* whether the
vaccination schedule
A vaccination schedule is a series of vaccinations, including the timing of all doses, which may be either recommended or compulsory, depending on the country of residence.
A vaccine is an antigenic preparation used to produce active immunity to ...
has been properly observed.
* idiosyncratic response to vaccination; some individuals are "non-responders" to certain vaccines, meaning that they do not generate antibodies even after being vaccinated correctly.
* assorted factors such as ethnicity, age, or genetic predisposition.
If a vaccinated individual does develop the disease vaccinated against (
breakthrough infection
A breakthrough infection is a case of illness in which a vaccinated individual becomes infected with the illness, because the vaccine has failed to provide complete immunity against the pathogen (currently only viruses). Breakthrough infections ha ...
), the disease is likely to be less virulent than in unvaccinated cases.
Important considerations in an effective vaccination program:
# careful modeling to anticipate the effect that an immunization campaign will have on the epidemiology of the disease in the medium to long term
# ongoing surveillance for the relevant disease following introduction of a new vaccine
# maintenance of high immunization rates, even when a disease has become rare
In 1958, there were 763,094 cases of measles in the United States; 552 deaths resulted.
After the introduction of new vaccines, the number of cases dropped to fewer than 150 per year (median of 56).
In early 2008, there were 64 suspected cases of measles. Fifty-four of those infections were associated with importation from another country, although only thirteen percent were actually acquired outside the United States; 63 of the 64 individuals either had never been vaccinated against measles or were uncertain whether they had been vaccinated.
Vaccines led to the eradication of
smallpox
Smallpox was an infectious disease caused by variola virus (often called smallpox virus) which belongs to the genus Orthopoxvirus. The last naturally occurring case was diagnosed in October 1977, and the World Health Organization (WHO) c ...
, one of the most contagious and deadly diseases in humans. Other diseases such as rubella,
polio
Poliomyelitis, commonly shortened to polio, is an infectious disease caused by the poliovirus. Approximately 70% of cases are asymptomatic; mild symptoms which can occur include sore throat and fever; in a proportion of cases more severe s ...
, measles, mumps,
chickenpox
Chickenpox, also known as varicella, is a highly contagious disease caused by the initial infection with varicella zoster virus (VZV). The disease results in a characteristic skin rash that forms small, itchy blisters, which eventually scab ...
, and
typhoid
Typhoid fever, also known as typhoid, is a disease caused by '' Salmonella'' serotype Typhi bacteria. Symptoms vary from mild to severe, and usually begin six to 30 days after exposure. Often there is a gradual onset of a high fever over several ...
are nowhere near as common as they were a hundred years ago thanks to widespread vaccination programs. As long as the vast majority of people are vaccinated, it is much more difficult for an outbreak of disease to occur, let alone spread. This effect is called
herd immunity
Herd immunity (also called herd effect, community immunity, population immunity, or mass immunity) is a form of indirect protection that applies only to contagious diseases. It occurs when a sufficient percentage of a population has become imm ...
. Polio, which is transmitted only among humans, is targeted by an extensive
eradication campaign that has seen endemic polio restricted to only parts of three countries (Afghanistan, Nigeria, and Pakistan).
However, the difficulty of reaching all children, cultural misunderstandings, and
disinformation
Disinformation is false information deliberately spread to deceive people. It is sometimes confused with misinformation, which is false information but is not deliberate.
The English word ''disinformation'' comes from the application of the L ...
have caused the anticipated eradication date to be missed several times.
Vaccines also help prevent the development of antibiotic resistance. For example, by greatly reducing the incidence of pneumonia caused by ''
Streptococcus pneumoniae
''Streptococcus pneumoniae'', or pneumococcus, is a Gram-positive, spherical bacteria, alpha-hemolytic (under aerobic conditions) or beta-hemolytic (under anaerobic conditions), aerotolerant anaerobic member of the genus Streptococcus. They are ...
'', vaccine programs have greatly reduced the prevalence of infections resistant to penicillin or other first-line antibiotics.
The measles vaccine is estimated to prevent a million deaths every year.
Adverse effects
Vaccinations given to children, adolescents, or adults are generally safe.
Adverse effects, if any, are generally mild.
The rate of side effects depends on the vaccine in question.
[ Some common side effects include fever, pain around the injection site, and muscle aches.][ Additionally, some individuals may be allergic to ingredients in the vaccine. ]MMR vaccine
The MMR vaccine is a vaccine against measles, mumps, and rubella (German measles), abbreviated as ''MMR''. The first dose is generally given to children around 9 months to 15 months of age, with a second dose at 15 months to 6 years of age, ...
is rarely associated with febrile seizure
A febrile seizure, also known as a fever fit or febrile convulsion, is a seizure associated with an increased body temperature but without any intracranial infection. Febrile seizures affect 2–7% of children and are more common in boys than gi ...
s.[
Host-("vaccinee")-related determinants that render a person susceptible to infection, such as ]genetics
Genetics is the study of genes, genetic variation, and heredity in organisms.Hartl D, Jones E (2005) It is an important branch in biology because heredity is vital to organisms' evolution. Gregor Mendel, a Moravian Augustinian friar wor ...
, health status (underlying disease, nutrition, pregnancy, sensitivities
Sensitivity may refer to:
Science and technology Natural sciences
* Sensitivity (physiology), the ability of an organism or organ to respond to external stimuli
** Sensory processing sensitivity in humans
* Sensitivity and specificity, statistica ...
or allergies
Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic derma ...
), immune competence, age, and economic impact
An economic impact analysis (EIA) examines the effect of an event on the economy in a specified area, ranging from a single neighborhood to the entire globe. It usually measures changes in business revenue, business profits, personal wages, and ...
or cultural environment
The social environment, social context, sociocultural context or milieu refers to the immediate physical and social setting in which people live or in which something happens or develops. It includes the culture that the individual was educate ...
can be primary or secondary factors affecting the severity of infection and response to a vaccine. Elderly (above age 60), allergen-hypersensitive, and obese
Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's we ...
people have susceptibility to compromised immunogenicity
Immunogenicity is the ability of a foreign substance, such as an antigen, to provoke an immune response in the body of a human or other animal. It may be wanted or unwanted:
* Wanted immunogenicity typically relates to vaccines, where the injectio ...
, which prevents or inhibits vaccine effectiveness, possibly requiring separate vaccine technologies for these specific populations or repetitive booster vaccinations to limit virus transmission.
Severe side effects are extremely rare.[ ]Varicella vaccine
Varicella vaccine, also known as chickenpox vaccine, is a vaccine that protects against chickenpox. One dose of vaccine prevents 95% of moderate disease and 100% of severe disease. Two doses of vaccine are more effective than one. If given to t ...
is rarely associated with complications in immunodeficient
Immunodeficiency, also known as immunocompromisation, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that a ...
individuals, and rotavirus vaccine
Rotavirus vaccine is a vaccine used to protect against rotavirus infections, which are the leading cause of severe diarrhea among young children. The vaccines prevent 15–34% of severe diarrhea in the developing world and 37–96% of se ...
s are moderately associated with intussusception.[
At least 19 countries have no-fault compensation programs to provide compensation for those with severe adverse effects of vaccination. The United States' program is known as the ]National Childhood Vaccine Injury Act
The National Childhood Vaccine Injury Act (NCVIA) of 1986 (42 U.S.C. §§ 300aa-1 to 300aa-34) was signed into law by United States President Ronald Reagan as part of a larger health bill on November 14, 1986. NCVIA's purpose was to eliminate t ...
, and the United Kingdom employs the Vaccine Damage Payment
The Vaccine Damage Payment is a provision of the welfare state in the United Kingdom that provides a substantial payment for people who can show that they have suffered a vaccine injury.
Description
The Vaccine Damage Payment program was create ...
.
Types
Vaccines typically contain attenuated, inactivated or dead organisms or purified products derived from them. There are several types of vaccines in use. These represent different strategies used to try to reduce the risk of illness while retaining the ability to induce a beneficial immune response.
Attenuated
Some vaccines contain live, attenuated microorganisms. Many of these are active viruses
A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea.
Since Dmitri Ivanovsky's 1 ...
that have been cultivated under conditions that disable their virulent properties, or that use closely related but less dangerous organisms to produce a broad immune response. Although most attenuated vaccines are viral, some are bacterial in nature. Examples include the viral diseases yellow fever
Yellow fever is a viral disease of typically short duration. In most cases, symptoms include fever, chills, loss of appetite, nausea, muscle pains – particularly in the back – and headaches. Symptoms typically improve within five days. In ...
, measles
Measles is a highly contagious infectious disease caused by measles virus. Symptoms usually develop 10–12 days after exposure to an infected person and last 7–10 days. Initial symptoms typically include fever, often greater than , cough, ...
, mumps
MUMPS ("Massachusetts General Hospital Utility Multi-Programming System"), or M, is an imperative, high-level programming language with an integrated transaction processing key–value database. It was originally developed at Massachusetts Gener ...
, and rubella
Rubella, also known as German measles or three-day measles, is an infection caused by the rubella virus. This disease is often mild, with half of people not realizing that they are infected. A rash may start around two weeks after exposure and ...
, and the bacterial disease typhoid
Typhoid fever, also known as typhoid, is a disease caused by '' Salmonella'' serotype Typhi bacteria. Symptoms vary from mild to severe, and usually begin six to 30 days after exposure. Often there is a gradual onset of a high fever over several ...
. The live ''Mycobacterium tuberculosis
Tuberculosis (TB) is an infectious disease usually caused by '' Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, in ...
'' vaccine developed by Calmette and Guérin is not made of a contagious
Contagious may refer to:
* Contagious disease
Literature
* Contagious (magazine), a marketing publication
* ''Contagious'' (novel), a science fiction thriller novel by Scott Sigler
Music
Albums
*''Contagious'' (Peggy Scott-Adams album), 1997
* ...
strain but contains a virulently modified strain called " BCG" used to elicit an immune response to the vaccine. The live attenuated vaccine containing strain ''Yersinia pestis
''Yersinia pestis'' (''Y. pestis''; formerly '' Pasteurella pestis'') is a gram-negative, non-motile, coccobacillus bacterium without spores that is related to both ''Yersinia pseudotuberculosis'' and ''Yersinia enterocolitica''. It is a facult ...
'' EV is used for plague immunization. Attenuated vaccines have some advantages and disadvantages. Attenuated, or live, weakened, vaccines typically provoke more durable immunological responses. But they may not be safe for use in immunocompromised individuals, and on rare occasions mutate to a virulent form and cause disease.
Inactivated
Some vaccines contain inactivated, but previously virulent, micro-organisms that have been destroyed with chemicals, heat, or radiation"ghosts", with intact but empty bacterial cell envelopes. They are considered an intermediate phase between the inactivated and attenuated vaccines. Examples include IPV (polio vaccine
Polio vaccines are vaccines used to prevent poliomyelitis (polio). Two types are used: an inactivated poliovirus given by injection (IPV) and a weakened poliovirus given by mouth (OPV). The World Health Organization (WHO) recommends all chil ...
), hepatitis A vaccine, rabies vaccine
The rabies vaccine is a vaccine used to prevent rabies. There are a number of rabies vaccines available that are both safe and effective. They can be used to prevent rabies before, and, for a period of time, after exposure to the rabies virus, ...
and most influenza vaccines
Influenza vaccines, also known as flu shots, are vaccines that protect against infection by influenza viruses. New versions of the vaccines are developed twice a year, as the influenza virus rapidly changes. While their effectiveness varies fro ...
.
Toxoid
Toxoid
A toxoid is an inactivated toxin (usually an exotoxin) whose toxicity has been suppressed either by chemical (formalin) or heat treatment, while other properties, typically immunogenicity, are maintained. Toxins are secreted by bacteria, wherea ...
vaccines are made from inactivated toxic compounds that cause illness rather than the micro-organism. Examples of toxoid-based vaccines include tetanus
Tetanus, also known as lockjaw, is a bacterial infection caused by ''Clostridium tetani'', and is characterized by muscle spasms. In the most common type, the spasms begin in the jaw and then progress to the rest of the body. Each spasm usually ...
and diphtheria
Diphtheria is an infection caused by the bacterium '' Corynebacterium diphtheriae''. Most infections are asymptomatic or have a mild clinical course, but in some outbreaks more than 10% of those diagnosed with the disease may die. Signs and s ...
. Not all toxoids are for micro-organisms; for example, ''Crotalus atrox
The western diamondback rattlesnake or Texas diamond-backWright AH, Wright AA. (1957). ''Handbook of Snakes''. Comstock Publishing Associates. (7th printing, 1985). . (''Crotalus atrox'') is a rattlesnake species and member of the viper family, ...
'' toxoid is used to vaccinate dogs against rattlesnake
Rattlesnakes are venomous snakes that form the genera ''Crotalus'' and ''Sistrurus'' of the subfamily Crotalinae (the pit vipers). All rattlesnakes are vipers. Rattlesnakes are predators that live in a wide array of habitats, hunting small anim ...
bites.
Subunit
Rather than introducing an inactivated or attenuated micro-organism to an immune system (which would constitute a "whole-agent" vaccine), a subunit
Subunit may refer to:
*Subunit HIV vaccine, a class of HIV vaccine
*Protein subunit, a protein molecule that assembles with other protein molecules
*Monomer, a molecule that may bind chemically to other molecules to form a polymer
*Sub-subunit, a ...
vaccine uses a fragment of it to create an immune response. One example is the subunit vaccine against hepatitisB, which is composed of only the surface proteins of the virus (previously extracted from the blood serum
Serum () is the fluid and solute component of blood which does not play a role in clotting. It may be defined as blood plasma without the clotting factors, or as blood with all cells and clotting factors removed. Serum includes all proteins not u ...
of chronically infected patients but now produced by recombination of the viral genes into yeast
Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are estimated to constitut ...
). Another example is edible algae vaccine Edible algae based vaccination is a vaccination strategy under preliminary research to combine a genetically engineered sub-unit vaccine and an immunologic adjuvant into ''Chlamydomonas reinhardtii'' microalgae. Microalgae can be freeze-dried and a ...
s, such as the virus-like particle
Virus-like particles (VLPs) are molecules that closely resemble viruses, but are non-infectious because they contain no viral genetic material. They can be naturally occurring or synthesized through the individual expression of viral structural pro ...
(VLP) vaccine against human papillomavirus
Human papillomavirus infection (HPV infection) is caused by a DNA virus from the ''Papillomaviridae'' family. Many HPV infections cause no symptoms and 90% resolve spontaneously within two years. In some cases, an HPV infection persists and res ...
(HPV), which is composed of the viral major capsid
A capsid is the protein shell of a virus, enclosing its genetic material. It consists of several oligomeric (repeating) structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or may ...
protein. Another example is the hemagglutinin
In molecular biology, hemagglutinins (or ''haemagglutinin'' in British English) (from the Greek , 'blood' + Latin , 'glue') are receptor-binding membrane fusion glycoproteins produced by viruses in the ''Paramyxoviridae'' family. Hemagglutinins ar ...
and neuraminidase
Exo-α-sialidase (EC 3.2.1.18, sialidase, neuraminidase; systematic name acetylneuraminyl hydrolase) is a glycoside hydrolase that cleaves the glycosidic linkages of neuraminic acids:
: Hydrolysis of α-(2→3)-, α-(2→6)-, α-(2→8)- glycos ...
subunits of the influenza
Influenza, commonly known as "the flu", is an infectious disease caused by influenza viruses. Symptoms range from mild to severe and often include fever, runny nose, sore throat, muscle pain, headache, coughing, and fatigue. These symptoms ...
virus. A subunit vaccine is being used for plague immunization.
Conjugate
Certain bacteria have a polysaccharide
Polysaccharides (), or polycarbohydrates, are the most abundant carbohydrates found in food. They are long chain polymeric carbohydrates composed of monosaccharide units bound together by glycosidic linkages. This carbohydrate can react with wa ...
outer coat that is poorly immunogenic
Immunogenicity is the ability of a foreign substance, such as an antigen, to provoke an immune response in the body of a human or other animal. It may be wanted or unwanted:
* Wanted immunogenicity typically relates to vaccines, where the injectio ...
. By linking these outer coats to proteins (e.g., toxins), the immune system
The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
can be led to recognize the polysaccharide as if it were a protein antigen. This approach is used in the ''Haemophilus influenzae'' type B vaccine.
Outer membrane vesicle
Outer membrane vesicles
Outer membrane vesicles (OMVs) are vesicles released from the outer membranes of Gram-negative bacteria. While Gram-positive bacteria release vesicles as well, those vesicles fall under the broader category of bacterial membrane vesicles (MVs) ...
(OMVs) are naturally immunogenic and can be manipulated to produce potent vaccines. The best known OMV vaccines are those developed for serotype B meningococcal disease.
Heterotypic
Heterologous vaccine A homologous booster shot involves the administration of the same vaccine as previously administered, while a heterologous booster shot involves the administration of a different vaccine.
"Heterologous prime-boost immunization is administration of ...
s also known as "Jennerian vaccines", are vaccines that are pathogens of other animals that either do not cause disease or cause mild disease in the organism being treated. The classic example is Jenner's use of cowpox to protect against smallpox. A current example is the use of BCG vaccine
Bacillus Calmette–Guérin (BCG) vaccine is a vaccine primarily used against tuberculosis (TB). It is named after its inventors Albert Calmette and Camille Guérin. In countries where tuberculosis or leprosy is common, one dose is recommended ...
made from ''Mycobacterium bovis
''Mycobacterium bovis'' is a slow-growing (16- to 20-hour generation time) aerobic bacterium and the causative agent of tuberculosis in cattle (known as bovine TB). It is related to ''Mycobacterium tuberculosis'', the bacterium which causes tube ...
'' to protect against tuberculosis
Tuberculosis (TB) is an infectious disease usually caused by '' Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, in ...
.
Genetic vaccine
The subgroup of genetic vaccine A genetic vaccine (also ''gene-based vaccine'') is a vaccine that contains nucleic acids such as DNA or RNA that lead to protein biosynthesis of antigens within a cell. Genetic vaccines thus include DNA vaccines, RNA vaccines and viral vector vaccin ...
s encompass viral vector vaccines, RNA vaccines and DNA vaccines.
Viral vector
Viral vector vaccines use a safe virus
A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea.
Since Dmitri Ivanovsky's 1 ...
to insert pathogen genes in the body to produce specific antigen
In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...
s, such as surface protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
s, to stimulate an immune response
An immune response is a reaction which occurs within an organism for the purpose of defending against foreign invaders. These invaders include a wide variety of different microorganisms including viruses, bacteria, parasites, and fungi which could ...
.
RNA
An mRNA vaccine (or RNA vaccine
An mRNA vaccine is a type of vaccine that uses a copy of a molecule called messenger RNA (mRNA) to produce an immune response. The vaccine delivers molecules of antigen-encoding mRNA into immune cells, which use the designed mRNA as a blueprin ...
) is a novel type of vaccine which is composed of the nucleic acid RNA, packaged within a vector such as lipid nanoparticles. Among the COVID-19 vaccine
A COVID19 vaccine is a vaccine intended to provide acquired immunity against severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2), the virus that causes coronavirus disease 2019 ( COVID19).
Prior to the COVID19 pandemic, an e ...
s are a number of RNA vaccines under development to combat the COVID-19 pandemic
The COVID-19 pandemic, also known as the coronavirus pandemic, is an ongoing global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The novel virus was first identif ...
and some have been approved or have received emergency use authorization
An Emergency Use Authorization (EUA) in the United States is an authorization granted to the Food and Drug Administration (FDA) under sections of the Federal Food, Drug, and Cosmetic Act as added to and amended by various Act of Congress, Acts of ...
in some countries. For example, the Pfizer-BioNTech vaccine and Moderna mRNA vaccine are approved for use in adults (with Pfizer vaccine also fully approved for teens aged 16 to 17) in the US.
DNA
DNA vaccination
A DNA vaccine is a type of vaccine that transfects a specific antigen-coding DNA sequence into the cells of an organism as a mechanism to induce an immune response.
DNA vaccines work by injecting genetically engineered plasmid containing the D ...
– The proposed mechanism is the insertion
Insertion may refer to:
*Insertion (anatomy), the point of a tendon or ligament onto the skeleton or other part of the body
*Insertion (genetics), the addition of DNA into a genetic sequence
*Insertion, several meanings in medicine, see ICD-10-PCS
...
and expression
Expression may refer to:
Linguistics
* Expression (linguistics), a word, phrase, or sentence
* Fixed expression, a form of words with a specific meaning
* Idiom, a type of fixed expression
* Metaphorical expression, a particular word, phrase, o ...
of viral or bacterial DNA in human or animal cells (enhanced by the use of electroporation
Electroporation, or electropermeabilization, is a microbiology technique in which an electrical field is applied to cells in order to increase the permeability of the cell membrane, allowing chemicals, drugs, electrode arrays or DNA to be introdu ...
), triggering immune system recognition. Some cells of the immune system that recognize the proteins expressed will mount an attack against these proteins and cells expressing them. Because these cells live for a very long time, if the pathogen
In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ ...
that normally expresses these proteins is encountered at a later time, they will be attacked instantly by the immune system. One potential advantage of DNA vaccines is that they are very easy to produce and store.
In August 2021, Indian authorities gave emergency approval to ZyCoV-D
ZyCoV-D is a DNA vaccine, DNA plasmid-based COVID-19 vaccine developed by Indian pharmaceutical company Cadila Healthcare, with support from the Biotechnology Industry Research Assistance Council. It is emergency use authorisation, approved ...
. Developed by Cadila Healthcare
Zydus Lifesciences Limited, formerly known as Cadila Healthcare Limited, is an Indian multinational pharmaceutical company headquartered in Ahmedabad, which is primarily engaged in the manufacture of generic drugs. It ranked 100th in the Fortu ...
, it is the first DNA vaccine approved for humans.
Experimental
Many innovative vaccines are also in development and use.
* Dendritic cell vaccines combine dendritic cell
Dendritic cells (DCs) are antigen-presenting cells (also known as ''accessory cells'') of the mammalian immune system. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. ...
s with antigens to present the antigens to the body's white blood cells, thus stimulating an immune reaction. These vaccines have shown some positive preliminary results for treating brain tumors and are also tested in malignant melanoma.
* Recombinant vector
Vector most often refers to:
*Euclidean vector, a quantity with a magnitude and a direction
*Vector (epidemiology), an agent that carries and transmits an infectious pathogen into another living organism
Vector may also refer to:
Mathematic ...
by combining the physiology of one micro-organism and the DNA of another, immunity can be created against diseases that have complex infection processes. An example is the RVSV-ZEBOV vaccine
Recombinant vesicular stomatitis virus–Zaire Ebola virus (rVSV-ZEBOV), also known as Ebola Zaire vaccine live and sold under the brand name Ervebo, is an Ebola vaccine for adults that prevents Ebola caused by the Zaire ebolavirus. When used ...
licensed to Merck that is being used in 2018 to combat ebola in Congo.
* T-cell receptor
The T-cell receptor (TCR) is a protein complex found on the surface of T cells, or T lymphocytes, that is responsible for recognizing fragments of antigen as peptides bound to major histocompatibility complex (MHC) molecules. The binding b ...
peptide vaccines are under development for several diseases using models of Valley Fever
A valley is an elongated low area often running between hills or mountains, which will typically contain a river or stream running from one end to the other. Most valleys are formed by erosion of the land surface by rivers or streams ove ...
, stomatitis
Stomatitis is inflammation of the mouth and lips. It refers to any inflammatory process affecting the mucous membranes of the mouth and lips, with or without oral ulceration.
In its widest meaning, stomatitis can have a multitude of different cau ...
, and atopic dermatitis
Atopic dermatitis (AD), also known as atopic eczema, is a long-term type of inflammation of the skin (dermatitis). It results in puritis, itchy, red, swollen, and cracked skin. Clear fluid may come from the affected areas, which often thickens o ...
. These peptides have been shown to modulate cytokine
Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...
production and improve cell-mediated immunity.
* Targeting of identified bacterial proteins that are involved in complement inhibition would neutralize the key bacterial virulence mechanism.
* The use of plasmid
A plasmid is a small, extrachromosomal DNA molecule within a cell that is physically separated from chromosomal DNA and can replicate independently. They are most commonly found as small circular, double-stranded DNA molecules in bacteria; how ...
s has been validated in preclinical studies as a protective vaccine strategy for cancer and infectious diseases. However, in human studies, this approach has failed to provide clinically relevant benefit. The overall efficacy of plasmid DNA immunization depends on increasing the plasmid's immunogenicity
Immunogenicity is the ability of a foreign substance, such as an antigen, to provoke an immune response in the body of a human or other animal. It may be wanted or unwanted:
* Wanted immunogenicity typically relates to vaccines, where the injectio ...
while also correcting for factors involved in the specific activation of immune effector cells.
* Bacterial vector – Similar in principle to viral vector vaccine
A viral vector vaccine is a vaccine that uses a viral vector to deliver genetic material ( DNA), which can be transcribed by the recipient's host cells as mRNA coding for a desired protein (or: antigen) to elicit an immune response. , six viral v ...
s, but using bacteria instead.
* Antigen-presenting cell
An antigen-presenting cell (APC) or accessory cell is a cell that displays antigen bound by major histocompatibility complex (MHC) proteins on its surface; this process is known as antigen presentation. T cells may recognize these complexes using ...
While most vaccines are created using inactivated or attenuated compounds from micro-organisms, synthetic vaccine A synthetic vaccine is a vaccine consisting mainly of synthetic peptides, carbohydrates, or antigens. They are usually considered to be safer than vaccines from bacterial cultures. Creating vaccines synthetically has the ability to increase the spe ...
s are composed mainly or wholly of synthetic peptides, carbohydrates, or antigens.
Valence
Vaccines may be ''monovalent'' (also called ''univalent'') or ''multivalent'' (also called ''polyvalent''). A monovalent vaccine is designed to immunize against a single antigen or single microorganism. A multivalent or polyvalent vaccine is designed to immunize against two or more strains of the same microorganism, or against two or more microorganisms. The valency of a multivalent vaccine may be denoted with a Greek or Latin prefix (e.g., ''bivalent'', ''trivalent'', or ''tetravalent/quadrivalent''). In certain cases, a monovalent vaccine may be preferable for rapidly developing a strong immune response.
When two or more vaccines are mixed in the same formulation, the two vaccines can interfere. This most frequently occurs with live attenuated vaccines, where one of the vaccine components is more robust than the others and suppresses the growth and immune response to the other components. This phenomenon was first noted in the trivalent Sabin polio vaccine
Polio vaccines are vaccines used to prevent poliomyelitis (polio). Two types are used: an inactivated poliovirus given by injection (IPV) and a weakened poliovirus given by mouth (OPV). The World Health Organization (WHO) recommends all chil ...
, where the amount of serotype2 virus in the vaccine had to be reduced to stop it from interfering with the "take" of the serotype1 and3 viruses in the vaccine. This phenomenon has also been found to be a problem with the dengue
Dengue fever is a mosquito-borne tropical disease caused by the dengue virus. Symptoms typically begin three to fourteen days after infection. These may include a high fever, headache, vomiting, muscle and joint pains, and a characteristic ...
vaccines currently being researched, where the DEN-3 serotype was found to predominate and suppress the response to DEN-1, -2 and -4 serotypes.
Other contents
Adjuvants
Vaccines typically contain one or more adjuvant In pharmacology, an adjuvant is a drug or other substance, or a combination of substances, that is used to increase the efficacy or potency of certain drugs. Specifically, the term can refer to:
* Adjuvant therapy in cancer management
* Analgesic ...
s, used to boost the immune response. Tetanus toxoid, for instance, is usually adsorbed onto alum
An alum () is a type of chemical compound, usually a hydrated double salt, double sulfate salt (chemistry), salt of aluminium with the general chemical formula, formula , where is a valence (chemistry), monovalent cation such as potassium or a ...
. This presents the antigen in such a way as to produce a greater action than the simple aqueous tetanus toxoid. People who have an adverse reaction to adsorbed tetanus toxoid may be given the simple vaccine when the time comes for a booster.
In the preparation for the 1990 Persian Gulf campaign, the whole cell pertussis
Whooping cough, also known as pertussis or the 100-day cough, is a highly contagious bacterial disease. Initial symptoms are usually similar to those of the common cold with a runny nose, fever, and mild cough, but these are followed by two or ...
vaccine was used as an adjuvant for anthrax
Anthrax is an infection caused by the bacterium ''Bacillus anthracis''. It can occur in four forms: skin, lungs, intestinal, and injection. Symptom onset occurs between one day and more than two months after the infection is contracted. The sk ...
vaccine. This produces a more rapid immune response than giving only the anthrax vaccine, which is of some benefit if exposure might be imminent.
Preservatives
Vaccines may also contain preservatives to prevent contamination with bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
or fungi
A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from ...
. Until recent years, the preservative thiomersal
Thiomersal (INN), or thimerosal (USAN, JAN), is an organomercury compound. It is a well-established antiseptic and antifungal agent.
The pharmaceutical corporation Eli Lilly and Company gave thiomersal the trade name Merthiolate. It has been u ...
( ''Thimerosal'' in the US and Japan) was used in many vaccines that did not contain live viruses. As of 2005, the only childhood vaccine in the U.S. that contains thiomersal in greater than trace amounts is the influenza vaccine, which is currently recommended only for children with certain risk factors. Single-dose influenza vaccines supplied in the UK do not list thiomersal in the ingredients. Preservatives may be used at various stages of the production of vaccines, and the most sophisticated methods of measurement might detect traces of them in the finished product, as they may in the environment and population as a whole.
Many vaccines need preservatives to prevent serious adverse effects such as ''Staphylococcus
''Staphylococcus'' is a genus of Gram-positive bacteria in the family Staphylococcaceae from the order Bacillales. Under the microscope, they appear spherical (cocci), and form in grape-like clusters. ''Staphylococcus'' species are facultative ...
'' infection, which in one 1928 incident killed 12 of 21 children inoculated with a diphtheria
Diphtheria is an infection caused by the bacterium '' Corynebacterium diphtheriae''. Most infections are asymptomatic or have a mild clinical course, but in some outbreaks more than 10% of those diagnosed with the disease may die. Signs and s ...
vaccine that lacked a preservative. Several preservatives are available, including thiomersal, phenoxyethanol
Phenoxyethanol is the organic compound with the formula C6H5OC2H4OH. It is a colorless oily liquid. It can be classified as a glycol ether and a phenol ether. It is a common preservative in vaccine formulations.
Use
Phenoxyethanol has germici ...
, and formaldehyde
Formaldehyde ( , ) (systematic name methanal) is a naturally occurring organic compound with the formula and structure . The pure compound is a pungent, colourless gas that polymerises spontaneously into paraformaldehyde (refer to section F ...
. Thiomersal is more effective against bacteria, has a better shelf-life, and improves vaccine stability, potency, and safety; but, in the U.S., the European Union
The European Union (EU) is a supranational political and economic union of member states that are located primarily in Europe. The union has a total area of and an estimated total population of about 447million. The EU has often been des ...
, and a few other affluent countries, it is no longer used as a preservative in childhood vaccines, as a precautionary measure due to its mercury
Mercury commonly refers to:
* Mercury (planet), the nearest planet to the Sun
* Mercury (element), a metallic chemical element with the symbol Hg
* Mercury (mythology), a Roman god
Mercury or The Mercury may also refer to:
Companies
* Merc ...
content. Although controversial claims have been made that thiomersal contributes to autism
The autism spectrum, often referred to as just autism or in the context of a professional diagnosis autism spectrum disorder (ASD) or autism spectrum condition (ASC), is a neurodevelopmental condition (or conditions) characterized by difficulti ...
, no convincing scientific evidence supports these claims. Furthermore, a 10–11-year study of 657,461 children found that the MMR vaccine does not cause autism and actually reduced the risk of autism by seven percent.
Excipients
Beside the active vaccine itself, the following excipient
An excipient is a substance formulated alongside the active ingredient of a medication, included for the purpose of long-term stabilization, bulking up solid formulations that contain potent active ingredients in small amounts (thus often referred ...
s and residual manufacturing compounds are present or may be present in vaccine preparations:
* Aluminum
Aluminium (aluminum in American and Canadian English) is a chemical element with the symbol Al and atomic number 13. Aluminium has a density lower than those of other common metals, at approximately one third that of steel. It has ...
salts or gels are added as adjuvant In pharmacology, an adjuvant is a drug or other substance, or a combination of substances, that is used to increase the efficacy or potency of certain drugs. Specifically, the term can refer to:
* Adjuvant therapy in cancer management
* Analgesic ...
s. Adjuvants are added to promote an earlier, more potent response, and more persistent immune response to the vaccine; they allow for a lower vaccine dosage.
* Antibiotic
An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...
s are added to some vaccines to prevent the growth of bacteria during production and storage of the vaccine.
* Egg protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
is present in the influenza vaccine
Influenza vaccines, also known as flu shots, are vaccines that protect against infection by influenza viruses. New versions of the vaccines are developed twice a year, as the influenza virus rapidly changes. While their effectiveness varies fr ...
and yellow fever vaccine
Yellow fever vaccine is a vaccine that protects against yellow fever. Yellow fever is a viral infection that occurs in Africa and South America. Most people begin to develop immunity within ten days of vaccination and 99 percent are protected ...
as they are prepared using chicken eggs. Other proteins may be present.
* Formaldehyde
Formaldehyde ( , ) (systematic name methanal) is a naturally occurring organic compound with the formula and structure . The pure compound is a pungent, colourless gas that polymerises spontaneously into paraformaldehyde (refer to section F ...
is used to inactivate bacterial products for toxoid vaccines. Formaldehyde is also used to inactivate unwanted viruses and kill bacteria that might contaminate the vaccine during production.
* Monosodium glutamate
Monosodium glutamate (MSG), also known as sodium glutamate, is the sodium salt of glutamic acid. MSG is found naturally in some foods including tomatoes and cheese in this glutamic acid form. MSG is used in cooking as a flavor enhancer wit ...
(MSG) and 2-phenoxyethanol
Phenoxyethanol is the organic compound with the formula C6H5OC2H4OH. It is a colorless oily liquid. It can be classified as a glycol ether and a phenol ether. It is a common preservative in vaccine formulations.
Use
Phenoxyethanol has germici ...
are used as stabilizers in a few vaccines to help the vaccine remain unchanged when the vaccine is exposed to heat, light, acidity, or humidity.
* Thiomersal
Thiomersal (INN), or thimerosal (USAN, JAN), is an organomercury compound. It is a well-established antiseptic and antifungal agent.
The pharmaceutical corporation Eli Lilly and Company gave thiomersal the trade name Merthiolate. It has been u ...
is a mercury-containing antimicrobial that is added to vials of vaccines that contain more than one dose to prevent contamination and growth of potentially harmful bacteria. Due to the controversy surrounding thiomersal, it has been removed from most vaccines except multi-use influenza, where it was reduced to levels so that a single dose contained less than a microgram of mercury, a level similar to eating ten grams of canned tuna.[The mercury levels in the table, unless otherwise indicated, are taken fro]
Mercury Levels in Commercial Fish and Shellfish (1990-2010)
U.S. Food and Drug Administration. Accessed 8January 2012.
Nomenclature
Various fairly standardized abbreviations for vaccine names have developed, although the standardization is by no means centralized or global. For example, the vaccine names used in the United States have well-established abbreviations that are also widely known and used elsewhere. An extensive list of them provided in a sortable table and freely accessible is available at a US Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georgi ...
web page. The page explains that "The abbreviations nthis table (Column 3) were standardized jointly by staff of the Centers for Disease Control and Prevention, ACIP Work Groups, the editor of the ''Morbidity and Mortality Weekly Report
The ''Morbidity and Mortality Weekly Report'' (''MMWR'') is a weekly epidemiological digest for the United States published by the Centers for Disease Control and Prevention (CDC). It was originally established as ''Weekly Health Index'' in 1930, ...
'' (MMWR), the editor of ''Epidemiology and Prevention of Vaccine-Preventable Diseases'' (the Pink Book), ACIP members, and liaison organizations to the ACIP."
Some examples are "DTaP
The DPT vaccine or DTP vaccine is a class of combination vaccines against three infectious diseases in humans: diphtheria, pertussis (whooping cough), and tetanus. The vaccine components include diphtheria and tetanus toxoids and either kille ...
" for diphtheria and tetanus toxoids and acellular
Non-cellular life, or acellular life is life that exists without a cellular structure for at least part of its life cycle. Historically, most (descriptive) definitions of life postulated that an organism must be composed of one or more cells, ...
pertussis vaccine, "DT" for diphtheria and tetanus toxoids, and "Td" for tetanus and diphtheria toxoids. At its page on tetanus vaccination, the CDC further explains that "Upper-case letters in these abbreviations denote full-strength doses of diphtheria (D) and tetanus (T) toxoids and pertussis (P) vaccine. Lower-case "d" and "p" denote reduced doses of diphtheria and pertussis used in the adolescent/adult-formulations. The 'a' in DTaP and Tdap stands for 'acellular', meaning that the pertussis component contains only a part of the pertussis organism."
Another list of established vaccine abbreviations is at the CDC's page called "Vaccine Acronyms and Abbreviations", with abbreviations used on U.S. immunization records. The United States Adopted Name
A United States Adopted Name (USAN) is a unique nonproprietary name assigned to a medication marketed in the United States. Each name is assigned by the USAN Council, which is co-sponsored by the American Medical Association (AMA), the United Stat ...
system has some conventions for the word order
In linguistics, word order (also known as linear order) is the order of the syntactic constituents of a language. Word order typology studies it from a cross-linguistic perspective, and examines how different languages employ different orders. C ...
of vaccine names, placing head nouns first and adjectives postpositively. This is why the USAN for " OPV" is "poliovirus vaccine live oral" rather than "oral poliovirus vaccine".
Licensing
A vaccine ''licensure'' occurs after the successful conclusion of the development cycle and further the clinical trials and other programs involved through PhasesI–III demonstrating safety, immunoactivity, immunogenetic safety at a given specific dose, proven effectiveness in preventing infection for target populations, and enduring preventive effect (time endurance or need for revaccination must be estimated). Because preventive vaccines are predominantly evaluated in healthy population cohorts and distributed among the general population, a high standard of safety is required. As part of a multinational licensing of a vaccine, the World Health Organization ''Expert Committee on Biological Standardization'' developed guidelines of international standards for manufacturing and quality control
Quality control (QC) is a process by which entities review the quality of all factors involved in production. ISO 9000 defines quality control as "a part of quality management focused on fulfilling quality requirements".
This approach places ...
of vaccines, a process intended as a platform for national regulatory agencies to apply for their own licensing process. Vaccine manufacturers do not receive licensing until a complete clinical cycle of development and trials proves the vaccine is safe and has long-term effectiveness, following scientific review by a multinational or national regulatory organization, such as the European Medicines Agency
The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Euro ...
(EMA) or the US Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
(FDA).
Upon developing countries
A developing country is a sovereign state with a lesser developed industrial base and a lower Human Development Index (HDI) relative to other countries. However, this definition is not universally agreed upon. There is also no clear agreem ...
adopting WHO guidelines for vaccine development and licensure, each country has its own responsibility to issue a national licensure, and to manage, deploy, and monitor the vaccine throughout its use in each nation. Building trust and acceptance of a licensed vaccine among the public is a task of communication by governments and healthcare personnel to ensure a vaccination campaign proceeds smoothly, saves lives, and enables economic recovery. When a vaccine is licensed, it will initially be in limited supply due to variable manufacturing, distribution, and logistical factors, requiring an allocation plan for the limited supply and which population segments should be prioritized to first receive the vaccine.
World Health Organization
Vaccines developed for multinational distribution via the United Nations Children's Fund (UNICEF) require pre-qualification by the WHO to ensure international standard
international standard is a technical standard developed by one or more international standards organizations. International standards are available for consideration and use worldwide. The most prominent such organization is the International Or ...
s of quality, safety, immunogenicity, and efficacy for adoption by numerous countries.
The process requires manufacturing consistency at WHO-contracted laboratories following Good Manufacturing Practice
Current good manufacturing practices (cGMP) are those conforming to the guidelines recommended by relevant agencies. Those agencies control the authorization and licensing of the manufacture and sale of food and beverages, cosmetics, pharmaceutica ...
(GMP). When UN agencies are involved in vaccine licensure, individual nations collaborate by 1) issuing marketing authorization and a national license for the vaccine, its manufacturers, and distribution partners; and 2) conducting postmarketing surveillance Postmarketing surveillance (PMS), also known as post market surveillance, is the practice of monitoring the safety of a pharmaceutical drug or medical device after it has been released on the market and is an important part of the science of pharmac ...
, including records for adverse events after the vaccination program. The WHO works with national agencies to monitor inspections of manufacturing facilities and distributors for compliance with GMP and regulatory oversight.
Some countries choose to buy vaccines licensed by reputable national organizations, such as EMA, FDA, or national agencies in other affluent countries, but such purchases typically are more expensive and may not have distribution resources suitable to local conditions in developing countries.
European Union
In the European Union (EU), vaccines for pandemic pathogens, such as seasonal influenza
Flu season is an annually recurring time period characterized by the prevalence of an outbreak of influenza (flu). The season occurs during the cold half of the year in each hemisphere. It takes approximately two days to show symptoms. Influen ...
, are licensed EU-wide where all the member states
A member state is a state that is a member of an international organization or of a federation or confederation.
Since the World Trade Organization (WTO) and the International Monetary Fund (IMF) include some members that are not sovereign states ...
comply ("centralized"), are licensed for only some member states ("decentralized"), or are licensed on an individual national level. Generally, all EU states follow regulatory guidance and clinical programs defined by the European Committee for Medicinal Products for Human Use
The Committee for Medicinal Products for Human Use (CHMP), formerly known as Committee for Proprietary Medicinal Products (CPMP), is the European Medicines Agency's committee responsible for elaborating the agency's opinions on all issues regarding ...
(CHMP), a scientific panel of the European Medicines Agency
The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Euro ...
(EMA) responsible for vaccine licensure. The CHMP is supported by several expert groups who assess and monitor the progress of a vaccine before and after licensure and distribution.
United States
Under the FDA, the process of establishing evidence for vaccine clinical safety and efficacy is the same as for the approval process for prescription drugs. If successful through the stages of clinical development, the vaccine licensing process is followed by a Biologics License Application
A biologics license application (BLA) is defined by the U.S. Food and Drug Administration (FDA) as follows:
The biologics license application is a request for permission to introduce, or deliver for introduction, a biologic product into inters ...
which must provide a scientific review team (from diverse disciplines, such as physicians, statisticians, microbiologists, chemists) and comprehensive documentation for the vaccine candidate having efficacy and safety throughout its development. Also during this stage, the proposed manufacturing facility is examined by expert reviewers for GMP compliance, and the label must have a compliant description to enable health care providers' definition of vaccine-specific use, including its possible risks, to communicate and deliver the vaccine to the public. After licensure, monitoring of the vaccine and its production, including periodic inspections for GMP compliance, continue as long as the manufacturer retains its license, which may include additional submissions to the FDA of tests for potency, safety, and purity for each vaccine manufacturing step.
India
Drugs Controller General of India is the head of department of the Central Drugs Standard Control Organization of the Government of India responsible for approval of licences of specified categories of drugs such as vaccines AND others like blood and blood products, IV fluids, and sera in India.
Postmarketing surveillance
Until a vaccine is in use for the general population, all potential adverse events
An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event can ther ...
from the vaccine may not be known, requiring manufacturers to conduct PhaseIV studies for postmarketing surveillance Postmarketing surveillance (PMS), also known as post market surveillance, is the practice of monitoring the safety of a pharmaceutical drug or medical device after it has been released on the market and is an important part of the science of pharmac ...
of the vaccine while it is used widely in the public. The WHO works with UN member states to implement post-licensing surveillance. The FDA relies on a Vaccine Adverse Event Reporting System
The Vaccine Adverse Event Reporting System (VAERS) is a United States program for vaccine safety, co-managed by the U.S. Centers for Disease Control and Prevention (CDC) and the Food and Drug Administration (FDA). VAERS is a postmarketing surveil ...
to monitor safety concerns about a vaccine throughout its use in the American public.
Scheduling
In order to provide the best protection, children are recommended to receive vaccinations as soon as their immune systems are sufficiently developed to respond to particular vaccines, with additional "booster" shots often required to achieve "full immunity". This has led to the development of complex vaccination schedules. Global recommendations of vaccination schedule are issued by Strategic Advisory Group of Experts The Strategic Advisory Group of Experts (SAGE) is the principal advisory group to World Health Organization (WHO) for vaccines and immunization. Established in 1999 through the merging of two previous committees, notably the Scientific Advisory Grou ...
and will be further translated by advisory committee
An advisory board is a body that provides non-binding strategic advice to the management of a corporation, organization, or foundation. The informal nature of an advisory board gives greater flexibility in structure and management compared to th ...
at the country level with considering of local factors such as disease epidemiology, acceptability of vaccination, equity in local populations, and programmatic and financial constraint. In the United States, the Advisory Committee on Immunization Practices
The Advisory Committee on Immunization Practices (ACIP) is a committee within the United States Centers for Disease Control and Prevention (CDC) that provides advice and guidance on effective control of vaccine-preventable diseases in the U.S. civ ...
, which recommends schedule additions for the Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georgi ...
, recommends routine vaccination of children against hepatitis A
Hepatitis A is an infectious disease of the liver caused by ''Hepatovirus A'' (HAV); it is a type of viral hepatitis. Many cases have few or no symptoms, especially in the young. The time between infection and symptoms, in those who develop them ...
, hepatitis B
Hepatitis B is an infectious disease caused by the ''Hepatitis B virus'' (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection.
Many people have no symptoms during an initial infection. Fo ...
, polio, mumps, measles, rubella, diphtheria
Diphtheria is an infection caused by the bacterium '' Corynebacterium diphtheriae''. Most infections are asymptomatic or have a mild clinical course, but in some outbreaks more than 10% of those diagnosed with the disease may die. Signs and s ...
, pertussis
Whooping cough, also known as pertussis or the 100-day cough, is a highly contagious bacterial disease. Initial symptoms are usually similar to those of the common cold with a runny nose, fever, and mild cough, but these are followed by two or ...
, tetanus
Tetanus, also known as lockjaw, is a bacterial infection caused by ''Clostridium tetani'', and is characterized by muscle spasms. In the most common type, the spasms begin in the jaw and then progress to the rest of the body. Each spasm usually ...
, HiB, chickenpox, rotavirus
''Rotavirus'' is a genus of double-stranded RNA viruses in the family ''Reoviridae''. Rotaviruses are the most common cause of diarrhoeal disease among infants and young children. Nearly every child in the world is infected with a rotavirus a ...
, influenza
Influenza, commonly known as "the flu", is an infectious disease caused by influenza viruses. Symptoms range from mild to severe and often include fever, runny nose, sore throat, muscle pain, headache, coughing, and fatigue. These symptoms ...
, meningococcal disease
Meningococcal disease describes infections caused by the bacterium ''Neisseria meningitidis'' (also termed meningococcus). It has a high mortality rate if untreated but is vaccine-preventable. While best known as a cause of meningitis, it can al ...
and pneumonia
Pneumonia is an inflammatory condition of the lung primarily affecting the small air sacs known as alveoli. Symptoms typically include some combination of productive or dry cough, chest pain, fever, and difficulty breathing. The severity ...
.
The large number of vaccines and boosters recommended (up to 24 injections by age two) has led to problems with achieving full compliance. To combat declining compliance rates, various notification systems have been instituted and many combination injections are now marketed (e.g., Pentavalent vaccine
A pentavalent vaccine, also known as a 5-in-1 vaccine, is a combination vaccine with five individual vaccines conjugated into one.
Pentavalent vaccine frequently refers to the 5-in-1 vaccine protecting against diphtheria, tetanus, whooping cough, ...
and MMRV vaccine
The MMRV vaccine combines the attenuated virus MMR (measles, mumps, rubella) vaccine with the addition of the chickenpox vaccine or varicella vaccine (V stands for varicella). The MMRV vaccine is typically given to children between one and two ...
), which protect against multiple diseases.
Besides recommendations for infant vaccinations and boosters, many specific vaccines are recommended for other ages or for repeated injections throughout lifemost commonly for measles, tetanus, influenza, and pneumonia. Pregnant women are often screened for continued resistance to rubella. The human papillomavirus
Human papillomavirus infection (HPV infection) is caused by a DNA virus from the ''Papillomaviridae'' family. Many HPV infections cause no symptoms and 90% resolve spontaneously within two years. In some cases, an HPV infection persists and res ...
vaccine is recommended in the U.S. (as of 2011) and UK (as of 2009). Vaccine recommendations for the elderly concentrate on pneumonia and influenza, which are more deadly to that group. In 2006, a vaccine was introduced against shingles
Shingles, also known as zoster or herpes zoster, is a viral disease characterized by a painful skin rash with blisters in a localized area. Typically the rash occurs in a single, wide mark either on the left or right side of the body or face. ...
, a disease caused by the chickenpox virus, which usually affects the elderly.
Scheduling and dosing of a vaccination may be tailored to the level of immunocompetence of an individual and to optimize population-wide deployment of a vaccine when it supply is limited, e.g. in the setting of a pandemic.
Economics of development
One challenge in vaccine development is economic: Many of the diseases most demanding a vaccine, including HIV
The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune ...
, malaria
Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. S ...
and tuberculosis, exist principally in poor countries. Pharmaceutical firms and biotechnology
Biotechnology is the integration of natural sciences and engineering sciences in order to achieve the application of organisms, cells, parts thereof and molecular analogues for products and services. The term ''biotechnology'' was first used b ...
companies have little incentive to develop vaccines for these diseases because there is little revenue potential. Even in more affluent countries, financial returns are usually minimal and the financial and other risks are great.
Most vaccine development to date has relied on "push" funding by government, universities and non-profit organizations. Many vaccines have been highly cost effective and beneficial for public health
Public health is "the science and art of preventing disease, prolonging life and promoting health through the organized efforts and informed choices of society, organizations, public and private, communities and individuals". Analyzing the det ...
. The number of vaccines actually administered has risen dramatically in recent decades. This increase, particularly in the number of different vaccines administered to children before entry into schools may be due to government mandates and support, rather than economic incentive.
Patents
According to the World Health Organization, the biggest barrier to vaccine production in less developed countries has not been patent
A patent is a type of intellectual property that gives its owner the legal right to exclude others from making, using, or selling an invention for a limited period of time in exchange for publishing an enabling disclosure of the invention."A p ...
s, but the substantial financial, infrastructure
Infrastructure is the set of facilities and systems that serve a country, city, or other area, and encompasses the services and facilities necessary for its economy, households and firms to function. Infrastructure is composed of public and priv ...
, and workforce requirements needed for market entry. Vaccines are complex mixtures of biological compounds, and unlike the case for prescription drug
A prescription drug (also prescription medication or prescription medicine) is a pharmaceutical drug that legally requires a medical prescription to be dispensed. In contrast, over-the-counter drugs can be obtained without a prescription. The rea ...
s, there are no true generic vaccines. The vaccine produced by a new facility must undergo complete clinical testing for safety and efficacy by the manufacturer. For most vaccines, specific processes in technology are patented. These can be circumvented by alternative manufacturing methods, but this required R&D infrastructure and a suitably skilled workforce. In the case of a few relatively new vaccines, such as the human papillomavirus
Human papillomavirus infection (HPV infection) is caused by a DNA virus from the ''Papillomaviridae'' family. Many HPV infections cause no symptoms and 90% resolve spontaneously within two years. In some cases, an HPV infection persists and res ...
vaccine, the patents may impose an additional barrier.
When increased production of vaccines was urgently needed during the COVID-19 pandemic
The COVID-19 pandemic, also known as the coronavirus pandemic, is an ongoing global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The novel virus was first identif ...
in 2021, the World Trade Organization
The World Trade Organization (WTO) is an intergovernmental organization that regulates and facilitates international trade. With effective cooperation
in the United Nations System, governments use the organization to establish, revise, and e ...
and governments around the world evaluated whether to waive intellectual property
Intellectual property (IP) is a category of property that includes intangible creations of the human intellect. There are many types of intellectual property, and some countries recognize more than others. The best-known types are patents, cop ...
rights and patents on COVID-19 vaccine
A COVID19 vaccine is a vaccine intended to provide acquired immunity against severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2), the virus that causes coronavirus disease 2019 ( COVID19).
Prior to the COVID19 pandemic, an e ...
s, which would "eliminate all potential barriers to the timely access of affordable COVID-19 medical products, including vaccines and medicines, and scale up the manufacturing and supply of essential medical products."
Production
Vaccine production is fundamentally different from other kinds of manufacturingincluding regular pharmaceutical manufacturing
Pharmaceutical manufacturing is the process of industrial-scale synthesis of pharmaceutical drugs as part of the pharmaceutical industry. The process of drug manufacturing can be broken down into a series of unit operations, such as milling, gra ...
in that vaccines are intended to be administered to millions of people of whom the vast majority are perfectly healthy. This fact drives an extraordinarily rigorous production process with strict compliance requirements that go far beyond what is required of other products.
Depending upon the antigen, it can cost anywhere from US$50 to $500 million to build a vaccine production facility, which requires highly specialized equipment, clean rooms
A cleanroom or clean room is an engineered space, which maintains a very low concentration of airborne particulates. It is well isolated, well-controlled from contamination, and actively cleansed. Such rooms are commonly needed for scientif ...
, and containment rooms. There is a global scarcity of personnel with the right combination of skills, expertise, knowledge, competence and personality to staff vaccine production lines. With the notable exceptions of Brazil, China, and India, many developing countries' educational systems are unable to provide enough qualified candidates, and vaccine makers based in such countries must hire expatriate personnel to keep production going.
Vaccine production has several stages. First, the antigen itself is generated. Viruses are grown either on primary cells such as chicken eggs
Humans and human ancestors have scavenged and eaten animal eggs for millions of years. Humans in Southeast Asia had domesticated chickens and harvested their eggs for food by 1,500 BCE. The most widely consumed eggs are those of fowl, especia ...
(e.g., for influenza) or on continuous cell lines such as cultured human cells (e.g., for hepatitis A
Hepatitis A is an infectious disease of the liver caused by ''Hepatovirus A'' (HAV); it is a type of viral hepatitis. Many cases have few or no symptoms, especially in the young. The time between infection and symptoms, in those who develop them ...
). Bacteria are grown in bioreactor
A bioreactor refers to any manufactured device or system that supports a biologically active environment. In one case, a bioreactor is a vessel in which a chemical reaction, chemical process is carried out which involves organisms or biochemistry, ...
s (e.g., ''Haemophilus influenzae
''Haemophilus influenzae'' (formerly called Pfeiffer's bacillus or ''Bacillus influenzae'') is a Gram-negative, non-motile, coccobacillary, facultatively anaerobic, capnophilic pathogenic bacterium of the family Pasteurellaceae. The bacteria ...
'' type b). Likewise, a recombinant protein derived from the viruses or bacteria can be generated in yeast, bacteria, or cell cultures.
After the antigen is generated, it is isolated from the cells used to generate it. A virus may need to be inactivated, possibly with no further purification required. Recombinant proteins need many operations involving ultrafiltration and column chromatography. Finally, the vaccine is formulated by adding adjuvant, stabilizers, and preservatives as needed. The adjuvant enhances the immune response to the antigen, stabilizers increase the storage life, and preservatives allow the use of multidose vials. Combination vaccines are harder to develop and produce, because of potential incompatibilities and interactions among the antigens and other ingredients involved.
The final stage in vaccine manufacture before distribution is fill and finish
In the pharmaceutical industry, fill and finish (also referred to as fill finish, fill-finish or fill/finish) is the process of filling vials with vaccine , biological and pharmaceutical Drug Substances (DS) and finishing the process of packaging t ...
, which is the process of filling vials with vaccines and packaging them for distribution. Although this is a conceptually simple part of the vaccine manufacture process, it is often a bottleneck in the process of distributing and administering vaccines.
Vaccine production techniques are evolving. Cultured mammalian cells
Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or ...
are expected to become increasingly important, compared to conventional options such as chicken eggs, due to greater productivity and low incidence of problems with contamination. Recombination technology that produces genetically detoxified vaccines is expected to grow in popularity for the production of bacterial vaccines that use toxoids. Combination vaccines are expected to reduce the quantities of antigens they contain, and thereby decrease undesirable interactions, by using pathogen-associated molecular pattern
Pathogen-associated molecular patterns (PAMPs) are small molecular motifs conserved within a class of microbes. They are recognized by toll-like receptors (TLRs) and other pattern recognition receptors (PRRs) in both plants and animals. A vast arra ...
s.
Vaccine manufacturers
The companies with the highest market share in vaccine production are Merck
Merck refers primarily to the German Merck family and three companies founded by the family, including:
* the Merck Group, a German chemical, pharmaceutical and life sciences company founded in 1668
** Merck Serono (known as EMD Serono in the Unite ...
, Sanofi
Sanofi S.A. is a French multinational pharmaceutical and healthcare company headquartered in Paris, France. Originally, the corporation was established in 1973 and merged with Synthélabo in 1999 to form Sanofi-Synthélabo. In 2004, Sanofi-Syn ...
, GlaxoSmithKline
GSK plc, formerly GlaxoSmithKline plc, is a British multinational pharmaceutical and biotechnology company with global headquarters in London, England. Established in 2000 by a merger of Glaxo Wellcome and SmithKline Beecham. GSK is the ten ...
, Pfizer
Pfizer Inc. ( ) is an American multinational pharmaceutical and biotechnology corporation headquartered on 42nd Street in Manhattan, New York City. The company was established in 1849 in New York by two German entrepreneurs, Charles Pfizer ...
and Novartis
Novartis AG is a Swiss-American multinational pharmaceutical corporation based in Basel, Switzerland and
Cambridge, Massachusetts, United States (global research).name="novartis.com">https://www.novartis.com/research-development/research-loc ...
, with 70% of vaccine sales concentrated in the EU or US (2013). Vaccine manufacturing plants require large capital investments ($50 million up to $300 million) and may take between 4 and 6 years to construct, with the full process of vaccine development taking between 10 and 15 years.[ Manufacturing in developing countries is playing an increasing role in supplying these countries, specifically with regards to older vaccines and in Brazil, India and China.][ The manufacturers in India are the most advanced in the developing world and include the ]Serum Institute of India
Serum Institute of India (SII) is an Indian biotechnology and biopharmaceuticals company, based in Pune. It is the world's largest manufacturer of vaccines. It was founded by Cyrus Poonawalla in 1966 and is a part of Cyrus Poonawalla Group.
O ...
, one of the largest producers of vaccines by number of doses and an innovator in processes, recently improving efficiency of producing the measles vaccine by 10 to 20-fold, due to switching to a MRC-5
MRC-5 ( Medical Research Council cell strain 5) is a diploid cell culture line composed of fibroblasts, originally developed from the lung tissue of a 14-week-old aborted Caucasian male fetus. The cell line was isolated by J.P. Jacobs and colle ...
cell culture instead of chicken eggs.[ China's manufacturing capabilities are focused on supplying their own domestic need, with Sinopharm (CNPGC) alone providing over 85% of the doses for 14 different vaccines in China.][ Brazil is approaching the point of supplying its own domestic needs using technology transferred from the developed world.][
]
Delivery systems
One of the most common methods of delivering vaccines into the human body is injection
Injection or injected may refer to:
Science and technology
* Injective function, a mathematical function mapping distinct arguments to distinct values
* Injection (medicine), insertion of liquid into the body with a syringe
* Injection, in broadca ...
.
The development of new delivery systems raises the hope of vaccines that are safer and more efficient to deliver and administer. Lines of research include liposome
A liposome is a small artificial vesicle, spherical in shape, having at least one lipid bilayer. Due to their hydrophobicity and/or hydrophilicity, biocompatibility, particle size and many other properties, liposomes can be used as drug deliver ...
s and ''ISCOM
Immune stimulating complexes (ISCOMs) are spherical open cage-like structures (typically 40 nm in diameter) that are spontaneously formed when mixing together cholesterol, phospholipids and Quillaja saponins under a specific stoichiometry. T ...
'' (immune stimulating complex).
Notable developments in vaccine delivery technologies have included oral vaccines. Early attempts to apply oral vaccines showed varying degrees of promise, beginning early in the 20th century, at a time when the very possibility of an effective oral antibacterial vaccine was controversial. By the 1930s there was increasing interest in the prophylactic value of an oral typhoid fever
Typhoid fever, also known as typhoid, is a disease caused by '' Salmonella'' serotype Typhi bacteria. Symptoms vary from mild to severe, and usually begin six to 30 days after exposure. Often there is a gradual onset of a high fever over several ...
vaccine for example.
An oral polio vaccine
Polio vaccines are vaccines used to prevent poliomyelitis (polio). Two types are used: an inactivated poliovirus given by injection (IPV) and a weakened poliovirus given by mouth (OPV). The World Health Organization (WHO) recommends all child ...
turned out to be effective when vaccinations were administered by volunteer staff without formal training; the results also demonstrated increased ease and efficiency of administering the vaccines. Effective oral vaccines have many advantages; for example, there is no risk of blood contamination. Vaccines intended for oral administration need not be liquid, and as solids, they commonly are more stable and less prone to damage or spoilage by freezing in transport and storage. Such stability reduces the need for a "cold chain
A cold chain is a low temperature-controlled supply chain network. An unbroken cold chain is an uninterrupted series of refrigerated production, storage and distribution activities, along with associated equipment and logistics, which maintain qu ...
": the resources required to keep vaccines within a restricted temperature range from the manufacturing stage to the point of administration, which, in turn, may decrease costs of vaccines.
A microneedle approach, which is still in stages of development, uses "pointed projections fabricated into arrays that can create vaccine delivery pathways through the skin".
An experimental needle-free vaccine delivery system is undergoing animal testing. A stamp-size patch similar to an adhesive bandage
An adhesive bandage, also called a sticking plaster, medical plaster, or simply plaster in British English, is a small medical dressing used for injuries not serious enough to require a full-size bandage. They are also known by the genericized tra ...
contains about 20,000 microscopic projections per square cm. This dermal
The dermis or corium is a layer of skin between the epidermis (with which it makes up the cutis) and subcutaneous tissues, that primarily consists of dense irregular connective tissue and cushions the body from stress and strain. It is divided in ...
administration potentially increases the effectiveness of vaccination, while requiring less vaccine than injection.
In veterinary medicine
Vaccinations of animals are used both to prevent their contracting diseases and to prevent transmission of disease to humans. Both animals kept as pets and animals raised as livestock are routinely vaccinated. In some instances, wild populations may be vaccinated. This is sometimes accomplished with vaccine-laced food spread in a disease-prone area and has been used to attempt to control rabies
Rabies is a viral disease that causes encephalitis in humans and other mammals. Early symptoms can include fever and tingling at the site of exposure. These symptoms are followed by one or more of the following symptoms: nausea, vomiting, vi ...
in raccoon
The raccoon ( or , ''Procyon lotor''), sometimes called the common raccoon to distinguish it from other species, is a mammal native to North America. It is the largest of the procyonid family, having a body length of , and a body weight of ...
s.
Where rabies occurs, rabies vaccination of dogs may be required by law. Other canine vaccines include canine distemper
Canine distemper virus (CDV) (sometimes termed footpad disease) is a viral disease that affects a wide variety of mammal families, including domestic and wild species of dogs, coyotes, foxes, pandas, wolves, ferrets, skunks, raccoons, and felin ...
, canine parvovirus
Canine parvovirus (also referred to as CPV, CPV2, or parvo) is a contagious virus mainly affecting dogs. CPV is highly contagious and is spread from dog to dog by direct or indirect contact with their feces. Vaccines can prevent this infection, ...
, infectious canine hepatitis
Infectious canine hepatitis (ICH) is an acute liver infection in dogs caused by ''Canine mastadenovirus A'', formerly called ''Canine adenovirus 1'' (CAV-1). CAV-1 also causes disease in wolves, coyotes, and bears, and encephalitis in foxes. The ...
, adenovirus-2, leptospirosis
Leptospirosis is a blood infection caused by the bacteria ''Leptospira''. Signs and symptoms can range from none to mild (headaches, muscle pains, and fevers) to severe ( bleeding in the lungs or meningitis). Weil's disease, the acute, severe ...
, ''Bordetella
''Bordetella'' () is a genus of small (0.2 – 0.7 µm), gram-negative coccobacilli of the phylum Pseudomonadota. ''Bordetella'' species, with the exception of '' B. petrii'', are obligate aerobes, as well as highly fastidious, or difficult ...
'', canine parainfluenza virus
Human parainfluenza viruses (HPIVs) are the viruses that cause human parainfluenza. HPIVs are a paraphyletic group of four distinct single-stranded RNA viruses belonging to the ''Paramyxoviridae'' family. These viruses are closely associated wit ...
, and Lyme disease
Lyme disease, also known as Lyme borreliosis, is a vector-borne disease caused by the ''Borrelia'' bacterium, which is spread by ticks in the genus ''Ixodes''. The most common sign of infection is an expanding red rash, known as erythema migran ...
, among others.
Cases of veterinary vaccines used in humans have been documented, whether intentional or accidental, with some cases of resultant illness, most notably with brucellosis
Brucellosis is a highly contagious zoonosis caused by ingestion of unpasteurized milk or undercooked meat from infected animals, or close contact with their secretions. It is also known as undulant fever, Malta fever, and Mediterranean fever.
The ...
. However, the reporting of such cases is rare and very little has been studied about the safety and results of such practices. With the advent of aerosol vaccination in veterinary clinics, human exposure to pathogens not naturally carried in humans, such as ''Bordetella bronchiseptica
''Bordetella bronchiseptica'' is a small, gram-negative, rod-shaped bacterium of the genus ''Bordetella''. It can cause infectious bronchitis in dogs and other animals, but rarely infects humans. Closely related to '' B. pertussis''—the obl ...
'', has likely increased in recent years. In some cases, most notably rabies
Rabies is a viral disease that causes encephalitis in humans and other mammals. Early symptoms can include fever and tingling at the site of exposure. These symptoms are followed by one or more of the following symptoms: nausea, vomiting, vi ...
, the parallel veterinary vaccine against a pathogen may be as much as orders of magnitude
An order of magnitude is an approximation of the logarithm of a value relative to some contextually understood reference value, usually 10, interpreted as the base of the logarithm and the representative of values of magnitude one. Logarithmic dis ...
more economical than the human one.
DIVA vaccines
DIVA (Differentiation of Infected from Vaccinated Animals), also known as SIVA (Segregation of Infected from Vaccinated Animals) vaccines, make it possible to differentiate between infected and vaccinated animals. DIVA vaccines carry at least one epitope
An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. The epitope is the specific piece of the antigen to which an antibody binds. The p ...
less than the equivalent wild microorganism. An accompanying diagnostic test that detects the antibody against that epitope assists in identifying whether the animal has been vaccinated or not.
The first DIVA vaccines (formerly termed marker vaccine A marker vaccine is a vaccine which allows for immunological differentiation (or segregation) of infected from vaccinated animals, and is also referred to as a DIVA (or SIVA) vaccine ifferentiation (or Segregation) of infected from vaccinated anim ...
s and since 1999 coined as DIVA vaccines) and companion diagnostic tests were developed by J. T. van Oirschot and colleagues at the Central Veterinary Institute in Lelystad, The Netherlands. They found that some existing vaccines against pseudorabies
Aujeszky's disease, usually called pseudorabies in the United States, is a viral disease in swine that has been endemic in most parts of the world. It is caused by ''Suid herpesvirus 1'' (SuHV-1). Aujeszky's disease is considered to be the mos ...
(also termed Aujeszky's disease) had deletions in their viral genome (among which was the gE gene). Monoclonal antibodies were produced against that deletion and selected to develop an ELISA
The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay uses a solid-phase type of enzyme immunoassay (EIA) to detect the presence ...
that demonstrated antibodies against gE. In addition, novel genetically engineered gE-negative vaccines were constructed. Along the same lines, DIVA vaccines and companion diagnostic tests against bovine herpesvirus1 infections have been developed.
The DIVA strategy has been applied in various countries to successfully eradicate pseudorabies virus from those countries. Swine populations were intensively vaccinated and monitored by the companion diagnostic test and, subsequently, the infected pigs were removed from the population. Bovine herpesvirus1 DIVA vaccines are also widely used in practice. Considerable efforts are ongoing to apply the DIVA principle to a wide range of infectious diseases, such as classical swine fever, avian influenza, ''Actinobacillus pleuropneumonia'' and ''Salmonella'' infections in pigs.
History
Prior to the introduction of vaccination with material from cases of cowpox (heterotypic immunisation), smallpox could be prevented by deliberate variolation
Variolation was the method of inoculation first used to immunize individuals against smallpox (''Variola'') with material taken from a patient or a recently variolated individual, in the hope that a mild, but protective, infection would result. Var ...
with smallpox virus. The earliest hints of the practice of variolation for smallpox in China come during the tenth century. The Chinese also practiced the oldest documented use of variolation, dating back to the fifteenth century. They implemented a method of "nasal insufflation
In religious and magical practice, insufflation and exsufflation are ritual acts of blowing, breathing, hissing, or puffing that signify variously expulsion or renunciation of evil or of the devil (the Evil One), or infilling or blessing with goo ...
" administered by blowing powdered smallpox material, usually scabs, up the nostrils. Various insufflation techniques have been recorded throughout the sixteenth and seventeenth centuries within China. Two reports on the Chinese practice of inoculation
Inoculation is the act of implanting a pathogen or other microorganism. It may refer to methods of artificially inducing immunity against various infectious diseases, or it may be used to describe the spreading of disease, as in "self-inoculati ...
were received by the Royal Society
The Royal Society, formally The Royal Society of London for Improving Natural Knowledge, is a learned society and the United Kingdom's national academy of sciences. The society fulfils a number of roles: promoting science and its benefits, re ...
in London in 1700; one by Martin Lister
Martin Lister FRS (12 April 1639 – 2 February 1712) was an English naturalist and physician. His daughters Anne and Susanna were two of his illustrators and engravers.
J. D. Woodley, ‘Lister , Susanna (bap. 1670, d. 1738)’, Oxford Dict ...
who received a report by an employee of the East India Company
The East India Company (EIC) was an English, and later British, joint-stock company founded in 1600 and dissolved in 1874. It was formed to trade in the Indian Ocean region, initially with the East Indies (the Indian subcontinent and Southea ...
stationed in China and another by Clopton Havers
Clopton Havers (24 February 1657 – April 1702) was an English physician who did pioneering research on the microstructure of bone. He is believed to have been the first person to observe and almost certainly the first to describe what are no ...
.
Mary Wortley Montagu
Lady Mary Wortley Montagu (née Pierrepont; 15 May 168921 August 1762) was an English aristocrat, writer, and poet. Born in 1689, Lady Mary spent her early life in England. In 1712, Lady Mary married Edward Wortley Montagu, who later served a ...
, who had witnessed variolation in Turkey, had her four-year-old daughter variolated in the presence of physicians of the Royal Court in 1721 upon her return to England. Later on that year, Charles Maitland conducted an experimental variolation of six prisoners in Newgate Prison
Newgate Prison was a prison at the corner of Newgate Street and Old Bailey Street just inside the City of London, England, originally at the site of Newgate, a gate in the Roman London Wall. Built in the 12th century and demolished in 1904, t ...
in London. The experiment was a success, and soon variolation was drawing attention from the royal family, who helped promote the procedure. However, in 1783, several days after Prince Octavius of Great Britain
Prince Octavius of Great Britain (23 February 17793 May 1783) was the thirteenth child and eighth son of King George III and his queen consort, Charlotte of Mecklenburg-Strelitz. Six months after the death of his younger brother Prince A ...
was inoculated, he died. In 1796, the physician
A physician (American English), medical practitioner (Commonwealth English), medical doctor, or simply doctor, is a health professional who practices medicine, which is concerned with promoting, maintaining or restoring health through th ...
Edward Jenner
Edward Jenner, (17 May 1749 – 26 January 1823) was a British physician and scientist who pioneered the concept of vaccines, and created the smallpox vaccine, the world's first vaccine. The terms ''vaccine'' and ''vaccination'' are derived f ...
took pus from the hand of a milkmaid with cowpox
Cowpox is an infectious disease caused by the ''cowpox virus'' (CPXV). It presents with large blisters in the skin, a fever and swollen glands, historically typically following contact with an infected cow, though in the last several decades more ...
, scratched it into the arm of an 8-year-old boy, James Phipps
James Phipps (1788 – 1853) was the first person given the experimental cowpox vaccine by Edward Jenner. Jenner knew of a local belief that dairy workers who had contracted a relatively mild infection called cowpox were immune to smallpox, and ...
, and six weeks later variolated the boy with smallpox, afterwards observing that he did not catch smallpox. Jenner extended his studies and, in 1798, reported that his vaccine was safe in children and adults, and could be transferred from arm-to-arm, which reduced reliance on uncertain supplies from infected cows. In 1804, the Spanish Balmis smallpox vaccination expedition to Spain's colonies Mexico and Philippines used the arm-to-arm transport method to get around the fact the vaccine survived for only 12 days ''in vitro
''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology an ...
''. They used cowpox. Since vaccination with cowpox was much safer than smallpox inoculation, the latter, though still widely practiced in England, was banned in 1840.
Following on from Jenner's work, the second generation of vaccines was introduced in the 1880s by Louis Pasteur
Louis Pasteur (, ; 27 December 1822 – 28 September 1895) was a French chemist and microbiologist renowned for his discoveries of the principles of vaccination, microbial fermentation and pasteurization, the latter of which was named afte ...
who developed vaccines for chicken cholera
Fowl cholera is also called avian cholera, avian pasteurellosis, avian hemorrhagic septicemia.
Abraham b.
It is the most common pasteurellosis of poultry. As the causative agent is ''Pasteurella multocida'', it is considered to be a zoonosis.
Adu ...
and anthrax
Anthrax is an infection caused by the bacterium ''Bacillus anthracis''. It can occur in four forms: skin, lungs, intestinal, and injection. Symptom onset occurs between one day and more than two months after the infection is contracted. The sk ...
, and from the late nineteenth century vaccines were considered a matter of national prestige. National vaccination policies were adopted and compulsory vaccination laws were passed. In 1931 Alice Miles Woodruff
Alice Miles Woodruff (November 29, 1900 – November 24, 1985), born Alice Lincoln Miles, was an American virologist. She developed a method for growing fowlpox outside of a live chicken alongside Ernest William Goodpasture. Her research greatly ...
and Ernest Goodpasture
Ernest William Goodpasture (October 17, 1886 – September 20, 1960) was an American pathologist and physician. Goodpasture advanced the scientific understanding of the pathogenesis of infectious diseases, parasitism, and a variety of ricketts ...
documented that the fowlpox
Fowlpox is the worldwide disease of poultry caused by viruses of the family ''Poxviridae'' and the genus ''Avipoxvirus''. The viruses causing fowlpox are distinct from one another but antigenically similar, possible hosts including chickens, tur ...
virus could be grown in embryonated Embryonated, unembryonated and de-embryonated are terms generally used in reference to eggs or, in botany, to seeds. The words are often used as professional jargon rather than as universally applicable terms or concepts. Examples of relevant fields ...
chicken egg
An egg is an organic vessel grown by an animal to carry a possibly fertilized egg cell (a zygote) and to incubate from it an embryo within the egg until the embryo has become an animal fetus that can survive on its own, at which point the a ...
. Soon scientists began cultivating other viruses in eggs. Eggs were used for virus propagation in the development of a yellow fever vaccine
Yellow fever vaccine is a vaccine that protects against yellow fever. Yellow fever is a viral infection that occurs in Africa and South America. Most people begin to develop immunity within ten days of vaccination and 99 percent are protected ...
in 1935 and an influenza vaccine
Influenza vaccines, also known as flu shots, are vaccines that protect against infection by influenza viruses. New versions of the vaccines are developed twice a year, as the influenza virus rapidly changes. While their effectiveness varies fr ...
in 1945. In 1959 growth media
A growth medium or culture medium is a solid, liquid, or semi-solid designed to support the growth of a population of microorganisms or cells via the process of cell proliferation or small plants like the moss ''Physcomitrella patens''. Different ...
and cell culture
Cell culture or tissue culture is the process by which cells are grown under controlled conditions, generally outside of their natural environment. The term "tissue culture" was coined by American pathologist Montrose Thomas Burrows. This te ...
replaced eggs as the standard method of virus propagation for vaccines.
Vaccinology flourished in the twentieth century, which saw the introduction of several successful vaccines, including those against diphtheria
Diphtheria is an infection caused by the bacterium '' Corynebacterium diphtheriae''. Most infections are asymptomatic or have a mild clinical course, but in some outbreaks more than 10% of those diagnosed with the disease may die. Signs and s ...
, measles
Measles is a highly contagious infectious disease caused by measles virus. Symptoms usually develop 10–12 days after exposure to an infected person and last 7–10 days. Initial symptoms typically include fever, often greater than , cough, ...
, mumps
MUMPS ("Massachusetts General Hospital Utility Multi-Programming System"), or M, is an imperative, high-level programming language with an integrated transaction processing key–value database. It was originally developed at Massachusetts Gener ...
, and rubella
Rubella, also known as German measles or three-day measles, is an infection caused by the rubella virus. This disease is often mild, with half of people not realizing that they are infected. A rash may start around two weeks after exposure and ...
. Major achievements included the development of the polio vaccine
Polio vaccines are vaccines used to prevent poliomyelitis (polio). Two types are used: an inactivated poliovirus given by injection (IPV) and a weakened poliovirus given by mouth (OPV). The World Health Organization (WHO) recommends all chil ...
in the 1950s and the eradication of smallpox
Smallpox was an infectious disease caused by variola virus (often called smallpox virus) which belongs to the genus Orthopoxvirus. The last naturally occurring case was diagnosed in October 1977, and the World Health Organization (WHO) cer ...
during the 1960s and 1970s. Maurice Hilleman
Maurice Ralph Hilleman (August 30, 1919 – April 11, 2005) was a leading American microbiologist who specialized in vaccinology and developed over 40 vaccines, an unparalleled record of productivity. According to one estimate, his vaccines ...
was the most prolific of the developers of the vaccines in the twentieth century. As vaccines became more common, many people began taking them for granted. However, vaccines remain elusive for many important diseases, including herpes simplex
Herpes simplex is a viral infection caused by the herpes simplex virus. Infections are categorized based on the part of the body infected.
Oral herpes involves the face or mouth. It may result in small blisters in groups often called cold ...
, malaria
Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. S ...
, gonorrhea
Gonorrhea, colloquially known as the clap, is a sexually transmitted infection (STI) caused by the bacterium '' Neisseria gonorrhoeae''. Infection may involve the genitals, mouth, or rectum. Infected men may experience pain or burning with ...
, and HIV
The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune ...
.
Generations of vaccines
First generation vaccines are whole-organism vaccineseither live and weakened, or killed forms. Live, attenuated vaccines, such as smallpox and polio vaccines, are able to induce killer T-cell
A cytotoxic T cell (also known as TC, cytotoxic T lymphocyte, CTL, T-killer cell, cytolytic T cell, CD8+ T-cell or killer T cell) is a T lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected by intracellular pa ...
(TC or CTL) responses, helper T-cell
The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are considere ...
(TH) responses and antibody
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
immunity
Immunity may refer to:
Medicine
* Immunity (medical), resistance of an organism to infection or disease
* ''Immunity'' (journal), a scientific journal published by Cell Press
Biology
* Immune system
Engineering
* Radiofrequence immunity desc ...
. However, attenuated forms of a pathogen
In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ ...
can convert to a dangerous form and may cause disease in immunocompromised
Immunodeficiency, also known as immunocompromisation, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that a ...
vaccine recipients (such as those with AIDS
Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual m ...
). While killed vaccines do not have this risk, they cannot generate specific killer T cell responses and may not work at all for some diseases.
Second generation vaccines were developed to reduce the risks from live vaccines. These are subunit vaccines, consisting of specific protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
antigen
In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...
s (such as tetanus
Tetanus, also known as lockjaw, is a bacterial infection caused by ''Clostridium tetani'', and is characterized by muscle spasms. In the most common type, the spasms begin in the jaw and then progress to the rest of the body. Each spasm usually ...
or diphtheria
Diphtheria is an infection caused by the bacterium '' Corynebacterium diphtheriae''. Most infections are asymptomatic or have a mild clinical course, but in some outbreaks more than 10% of those diagnosed with the disease may die. Signs and s ...
toxoid
A toxoid is an inactivated toxin (usually an exotoxin) whose toxicity has been suppressed either by chemical (formalin) or heat treatment, while other properties, typically immunogenicity, are maintained. Toxins are secreted by bacteria, wherea ...
) or recombinant protein components (such as the hepatitis B surface antigen). They can generate TH and antibody responses, but not killer T cell responses.
RNA vaccine
An mRNA vaccine is a type of vaccine that uses a copy of a molecule called messenger RNA (mRNA) to produce an immune response. The vaccine delivers molecules of antigen-encoding mRNA into immune cells, which use the designed mRNA as a blueprin ...
s and DNA vaccine
A DNA vaccine is a type of vaccine that transfects a specific antigen-coding DNA sequence into the cells of an organism as a mechanism to induce an immune response.
DNA vaccines work by injecting genetically engineered plasmid containing the D ...
s are examples of third generation vaccines. In 2016 a DNA vaccine for the Zika virus
''Zika virus'' (ZIKV; pronounced or ) is a member of the virus family ''Flaviviridae''. It is spread by daytime-active ''Aedes'' mosquitoes, such as '' A. aegypti'' and '' A. albopictus''. Its name comes from the Ziika Forest of Uganda, whe ...
began testing at the National Institutes of Health
The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...
. Separately, Inovio Pharmaceuticals and GeneOne Life Science began tests of a different DNA vaccine against Zika in Miami. Manufacturing the vaccines in volume was unsolved as of 2016. Clinical trials for DNA vaccines to prevent HIV are underway. mRNA vaccines
An mRNA vaccine is a type of vaccine that uses a copy of a molecule called messenger RNA (mRNA) to produce an immune response. The vaccine RNA transfection, delivers molecules of antigen-encoding mRNA into dendritic cell, immune cells, which us ...
such as BNT162b2 were developed in the year 2020 with the help of Operation Warp Speed
Operation Warp Speed (OWS) was a public–private partnership initiated by the United States government to facilitate and accelerate the development, manufacturing, and distribution of COVID-19 vaccines, therapeutics, and diagnostics. The firs ...
and massively deployed to combat the COVID-19 pandemic
The COVID-19 pandemic, also known as the coronavirus pandemic, is an ongoing global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The novel virus was first identif ...
. In 2021, Katalin Karikó
Katalin Karikó ( hu, Karikó Katalin, ; born 17 January 1955) is a Hungarian-American biochemist who specializes in RNA-mediated mechanisms. Her research has been the development of in vitro- transcribed mRNA for protein therapies. She co-fo ...
and Drew Weissman
Drew Weissman (born 1959) is an American physician-scientist best known for his contributions to RNA biology. His work helped enable development of effective mRNA vaccines, the best known of which are those for COVID-19 produced by BioNTech/P ...
received Columbia University's Horwitz Prize for their pioneering research in mRNA vaccine technology.
Trends
Since at least 2013, scientists have been trying to develop synthetic third-generation vaccines by reconstructing the outside structure of a virus
A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea.
Since Dmitri Ivanovsky's 1 ...
; it was hoped that this will help prevent vaccine resistance
Vaccine resistance is the evolutionary adaptation of pathogens to infect and spread through vaccinated individuals, analogous to antimicrobial resistance. It concerns both human and animal vaccines. Although the emergence of a number of vaccine ...
.
Principles that govern the immune response can now be used in tailor-made vaccines against many noninfectious human diseases, such as cancers and autoimmune disorders. For example, the experimental vaccine CYT006-AngQb
CYT006-AngQb was an investigational vaccine against angiotensin II, designed to lower blood pressure. It was somewhat effective in clinical trials, but less so than conventional drugs against hypertension (elevated blood pressure).
Method of ...
has been investigated as a possible treatment for high blood pressure
Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...
. Factors that affect the trends of vaccine development include progress in translatory medicine, demographics
Demography () is the statistical study of populations, especially human beings.
Demographic analysis examines and measures the dimensions and dynamics of populations; it can cover whole societies or groups defined by criteria such as edu ...
, regulatory science Regulatory science is the scientific and technical foundations upon which regulations are based in various industries – particularly those involving health or safety. Regulatory bodies employing such principles in the United States include, for ex ...
, political, cultural, and social responses.
Plants as bioreactors for vaccine production
The idea of vaccine production via transgenic plants
Genetically modified plants have been engineered for scientific research, to create new colours in plants, deliver vaccines, and to create enhanced crops. Plant genomes can be engineered by physical methods or by use of ''Agrobacterium'' for the ...
was identified as early as 2003. Plants such as tobacco
Tobacco is the common name of several plants in the genus '' Nicotiana'' of the family Solanaceae, and the general term for any product prepared from the cured leaves of these plants. More than 70 species of tobacco are known, but the ...
, potato
The potato is a starchy food, a tuber of the plant ''Solanum tuberosum'' and is a root vegetable native to the Americas. The plant is a perennial in the nightshade family Solanaceae.
Wild potato species can be found from the southern Unit ...
, tomato
The tomato is the edible berry of the plant ''Solanum lycopersicum'', commonly known as the tomato plant. The species originated in western South America, Mexico, and Central America. The Mexican Nahuatl word gave rise to the Spanish word ...
, and banana
A banana is an elongated, edible fruit – botanically a berry – produced by several kinds of large herbaceous flowering plants in the genus ''Musa''. In some countries, bananas used for cooking may be called "plantains", distinguis ...
can have genes inserted that cause them to produce vaccines usable for humans. In 2005, bananas were developed that produce a human vaccine against hepatitis B
Hepatitis B is an infectious disease caused by the ''Hepatitis B virus'' (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection.
Many people have no symptoms during an initial infection. Fo ...
.
Vaccine hesitancy
Vaccine hesitancy
Vaccine hesitancy is a delay in acceptance, or refusal, of vaccines despite the availability of vaccine services and supporting evidence. The term covers refusals to vaccinate, delaying vaccines, accepting vaccines but remaining uncertain abou ...
is a delay in acceptance, or refusal of vaccines despite the availability of vaccine services. The term covers outright refusals to vaccinate, delaying vaccines, accepting vaccines but remaining uncertain about their use, or using certain vaccines but not others. There is an overwhelming scientific consensus
Scientific consensus is the generally held judgment, position, and opinion of the majority or the supermajority of scientists in a particular field of study at any particular time.
Consensus is achieved through scholarly communication at confe ...
that vaccines are generally safe and effective. Vaccine hesitancy often results in disease outbreak
In epidemiology, an outbreak is a sudden increase in occurrences of a disease when cases are in excess of normal expectancy for the location or season. It may affect a small and localized group or impact upon thousands of people across an entire ...
s and deaths from vaccine-preventable diseases A vaccine-preventable disease is an infectious disease for which an effective preventive vaccine exists. If a person acquires a vaccine-preventable disease and dies from it, the death is considered a vaccine-preventable death.
The most common and s ...
. The World Health Organization
The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...
therefore characterized vaccine hesitancy as one of the top ten global health threats in 2019.
See also
* Biologics Control Act
The Biologics Control Act of 1902, also known as the Virus-Toxin Law, was the first law that implemented federal regulations of biological products such as vaccines in the United States. It was enacted in response to two incidents involving the d ...
* Coalition for Epidemic Preparedness Innovations
The Coalition for Epidemic Preparedness Innovations (CEPI) is a foundation that takes donations from public, private, philanthropic, and civil society organisations, to finance independent research projects to develop vaccines against emerging ...
* Flying syringe
Flying syringe is a phrase that is used to refer to proposed, but not yet created, genetically modified mosquitoes that inject vaccines into people when they bite them.
History
In the 1990s, Bob Sinden of Imperial College, London, and Julian Cramp ...
* Immunization registry
An immunization registry or immunization information system (IIS) is an information system that collects vaccination data about all persons within a geographic area. It consolidates the immunization records from multiple sources for each person li ...
* Immunotherapy
Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as ''activation immunotherapies,'' while immunotherap ...
* List of vaccine ingredients
This is a list of excipients per vaccine, as published by the United States Centers for Disease Control. Vaccine ingredients and production in other nations are substantially the same. Also listed are substances used in the manufacturing process. ...
* List of vaccine topics
This is a list of vaccine-related topics.
A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened ...
* Non-specific effect of vaccines
Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than normal, raised or lowered blood pressure or an abnormality showin ...
* OPV AIDS hypothesis
The oral polio vaccine (OPV) AIDS hypothesis is a now-discredited hypothesis that the AIDS pandemic originated from live polio vaccines prepared in Common chimpanzee, chimpanzee tissue cultures, accidentally contaminated with simian immunodeficie ...
* Preventive healthcare
Preventive healthcare, or prophylaxis, consists of measures taken for the purposes of disease prevention.Hugh R. Leavell and E. Gurney Clark as "the science and art of preventing disease, prolonging life, and promoting physical and mental hea ...
* Reverse vaccinology
Reverse vaccinology is an improvement of vaccinology that employs bioinformatics and reverse pharmacology practices, pioneered by Rino Rappuoli and first used against Serogroup B meningococcus. Since then, it has been used on several other bact ...
* TA-CD TA-CD is an active vaccine developed by the Xenova Group which is used to negate the effects of cocaine, making it suitable for use in treatment of addiction. It is created by combining norcocaine with inactivated cholera toxin.
It works in much th ...
* Timeline of vaccines
This is a timeline of the development of prophylactic human vaccines. Early vaccines may be listed by the first year of development or testing, but later entries usually show the year the vaccine finished trials and became available on the market. ...
* Virosome
A virosome is a drug or vaccine delivery mechanism consisting of unilamellar phospholipid membrane (either a mono- or bi-layer) vesicle incorporating virus derived proteins to allow the virosomes to fuse with target cells. Viruses are infectious ...
* Vaccinator
A vaccinator is a person who gives injections of a vaccine to people. Vaccinators require the skills of knowing where to inject the needle into the recipient as well as preparing the substance to be injected.
Under normal conditions, routine inoc ...
* Vaccine adverse event
A vaccine adverse event (VAE), sometimes referred to as a vaccine injury, is an adverse event caused by vaccination. The World Health Organization (WHO) knows VAEs as Adverse Events Following Immunization (AEFI).
AEFIs can be related to the vacci ...
(safety issues)
* Vaccine cooler Many vaccines require refrigeration to remain active, and the lack of infrastructure to maintain the cool chain to reliably bring vaccines into more remote areas of developing countries poses a serious challenge to national immunization programs. Po ...
* Vaccine failure
Vaccination is the administration of a vaccine to help the immune system develop immunity from a disease. Vaccines contain a microorganism or virus in a weakened, live or killed state, or proteins or toxins from the organism. In stimulating ...
* Vaccine hesitancy
Vaccine hesitancy is a delay in acceptance, or refusal, of vaccines despite the availability of vaccine services and supporting evidence. The term covers refusals to vaccinate, delaying vaccines, accepting vaccines but remaining uncertain abou ...
* Vaccinov
Smallpox was an infectious disease caused by variola virus (often called smallpox virus) which belongs to the genus Orthopoxvirus. The last naturally occurring case was diagnosed in October 1977, and the World Health Organization (WHO) cer ...
* Viral vector
Viral vectors are tools commonly used by molecular biologists to deliver genetic material into cells. This process can be performed inside a living organism (''in vivo'') or in cell culture (''in vitro''). Viruses have evolved specialized molecul ...
* Virus-like particle
Virus-like particles (VLPs) are molecules that closely resemble viruses, but are non-infectious because they contain no viral genetic material. They can be naturally occurring or synthesized through the individual expression of viral structural pro ...
* Nasal vaccine
A nasal vaccine is a vaccine administered to a person via the nose and does not require a needle. It induces immunity through the inner surface of the nose, a surface that naturally comes in contact with many airborne microbes.
Administration
A ...
References
External links
*
WHO Vaccine preventable diseases and immunization
World Health Organization position papers on vaccines
The History of Vaccines
from the College of Physicians of Philadelphia
The College of Physicians of Philadelphia is the oldest private medical society in the United States. Founded in 1787 by 24 Philadelphia physicians "to advance the Science of Medicine, and thereby lessen human misery, by investigating the disease ...
*: This website was highlighted by ''Genetic Engineering & Biotechnology News'' in its "Best of the Web" section in January 2015. See:
{{Authority control
Virology
18th-century inventions