An inactivated vaccine (or killed vaccine) is a

vaccine 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 ...

consisting of

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 ...

particles,

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 other

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 ...

s that have been grown in

culture Culture () is an umbrella term which encompasses the social behavior, institutions, and norms found in human societies, as well as the knowledge, beliefs, arts, laws, customs, capabilities, and habits of the individuals in these groups.Tyl ...

and then killed to destroy disease-producing capacity. In contrast,

live vaccines Live may refer to: Arts, entertainment, and media Films * ''Live!'' (2007 film), 2007 American film * ''Live'' (2014 film), a 2014 Japanese film *'' ''Live'' (Apocalyptica DVD) Music *Live (band), American alternative rock band * List of albums ...

use pathogens that are still alive (but are almost always attenuated, that is, weakened). Pathogens for inactivated vaccines are grown under controlled conditions and are killed as a means to reduce infectivity and thus prevent

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 ...

from the vaccine. Inactivated vaccines were first developed in the late 1800s and early 1900s for

cholera Cholera is an infection of the small intestine by some strains of the bacterium ''Vibrio cholerae''. Symptoms may range from none, to mild, to severe. The classic symptom is large amounts of watery diarrhea that lasts a few days. Vomiting and ...

plague Plague or The Plague may refer to: Agriculture, fauna, and medicine *Plague (disease), a disease caused by ''Yersinia pestis'' * An epidemic of infectious disease (medical or agricultural) * A pandemic caused by such a disease * A swarm of pes ...

, 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 ...

. Today, inactivated vaccines exist for many pathogens, including

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 ...

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 ...

(IPV),

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 ...

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 ...

and

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 ...

. Because inactivated pathogens tend to produce a weaker response by the immune system than live pathogens,

immunologic adjuvant In immunology, an adjuvant is a substance that increases or modulates the immune response to a vaccine. The word "adjuvant" comes from the Latin word ''adiuvare'', meaning to help or aid. "An immunologic adjuvant is defined as any substance that ...

s and multiple "

booster Booster may refer to: Amusement rides * Booster (Fabbri ride), a pendulum ride * Booster (HUSS ride), an evolution of the Breakdance ride * Booster (KMG ride), a pendulum ride Arts, entertainment, and media Fictional characters *Booster, a char ...

" injections may be required in some vaccines to provide an effective immune response against the pathogen. Attenuated vaccines are often preferable for generally healthy people because a single dose is often safe and very effective. However, some people cannot take attenuated vaccines because the pathogen poses too much risk for them (for example,

elderly people Old age refers to ages nearing or surpassing the life expectancy of human beings, and is thus the end of the human life cycle. Terms and euphemisms for people at this age include old people, the elderly (worldwide usage), OAPs (British usage ...

or people with

immunodeficiency 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 ...

). For those patients, an inactivated vaccine can provide protection.

Mechanism

The pathogen particles are destroyed and cannot divide, but the pathogens maintain some of their integrity to be recognized by the immune system and evoke an adaptive immune response. When manufactured correctly, the vaccine is not infectious, but improper inactivation can result in intact and infectious particles. When a vaccine is administered, the

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. ...

will be taken up by an

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 ...

(APC) and transported to a draining lymph node in vaccinated people. The APC will place a piece of the antigen, an

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 ...

, on its surface along with a major histocompatibility complex (MHC) molecule. It can now interact with and activate T cells. The resulting helper T cells will then stimulate an antibody-mediated or

cell-mediated Cell-mediated immunity or cellular immunity is an immune response that does not involve antibodies. Rather, cell-mediated immunity is the activation of phagocytes, antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in ...

immune response and develop an antigen-specific

adaptive Adaptation, in biology, is the process or trait by which organisms or population better match their environment Adaptation may also refer to: Arts * Adaptation (arts), a transfer of a work of art from one medium to another ** Film adaptation, a ...

response. This process creates an

immunological memory Immunological memory is the ability of the immune system to quickly and specifically recognize an antigen that the body has previously encountered and initiate a corresponding immune response. Generally, these are secondary, tertiary and other subs ...

against the specific pathogen and allows the immune system to respond more effectively and rapidly after subsequent encounters with that pathogen. Inactivated vaccines tend to produce an immune response that is primarily antibody-mediated. However, deliberate adjuvant selection allows inactivated vaccines to stimulate a more robust cell-mediated immune response.

Types

''Inactivated vaccines'' often refer to ''non-live vaccines.'' They are further classified depending on the method used to inactivate the pathogen: * ''Whole pathogen inactivated vaccines'' are produced when an entire pathogen is 'killed' using heat, chemicals, or radiation, although only

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 ...

and

beta-Propiolactone β-Propiolactone is an organic compound of the lactone family, with a four-membered ring. It is a colorless liquid with a slightly sweet odor, highly soluble in water and miscible with ethanol, acetone, diethyl ether and chloroform.''Merck Index' ...

exposure are widely used in human vaccines. * ''

Subunit vaccine A subunit vaccine is a vaccine that contains purified parts of the pathogen that are antigenic, or necessary to elicit a protective immune response. A "subunit" vaccine doesn't contain the whole pathogen, unlike live attenuated or inactivated va ...

s'' are produced by purifying out the

antigens 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. ...

that best stimulate 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 ...

to mount a response to the pathogen, while removing other components necessary for the pathogen to replicate or survive or that can cause

adverse reaction An adverse effect is an undesired harmful effect resulting from a medication or other intervention, such as surgery. An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. The term complica ...

s. *''Split virus vaccines'' are produced by using a detergent to disrupt the

viral envelope A viral envelope is the outermost layer of many types of viruses. It protects the genetic material in their life cycle when traveling between host cells. Not all viruses have envelopes. Numerous human pathogenic viruses in circulation are encase ...

. This technique is used in the development of many

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 vaccines 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 ...

'' are created by inactivating

toxins A toxin is a naturally occurring organic poison produced by metabolic activities of living cells or organisms. Toxins occur especially as a protein or conjugated protein. The term toxin was first used by organic chemist Ludwig Brieger (1849–1 ...

produced by bacteria. The toxoid mounts an immune response against the toxin.

Examples

Types include: * Viral: ** Injected

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 ...

(

Salk 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 Hepatitis A vaccine is a vaccine that prevents hepatitis A.Lay summary
...

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, ...

** Most

Tick-borne encephalitis vaccine Tick-borne encephalitis vaccine is a vaccine used to prevent tick-borne encephalitis (TBE). The disease is most common in Central and Eastern Europe, and Northern Asia. More than 87% of people who receive the vaccine develop immunity. It is not ...

** Some

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 ...

CoronaVac CoronaVac, also known as the Sinovac COVID-19 vaccine, is a whole inactivated virus COVID-19 vaccine developed by the Chinese company Sinovac Biotech. It was Phase III clinical trialled in Brazil, Chile, Indonesia, the Philippines, and Turke ...

Covaxin Covaxin (codenamed as BBV152) is a whole inactivated virus-based COVID-19 vaccine developed by Bharat Biotech in collaboration with the Indian Council of Medical Research - National Institute of Virology. As of October 2021, 110.6 million ...

QazVac QazCovid-in, commercially known as QazVac, is a COVID-19 vaccine developed by the Research Institute for Biological Safety Problems in Kazakhstan. QazCoVac-P is a second COVID-19 vaccine developed by the Kazakh Biosafety Research Institute and ...

, Sinopharm BIBP, Sinopharm WIBP, TURKOVAC, CoviVac * Bacterial: ** Injected

typhoid vaccine Typhoid vaccines are vaccines that prevent typhoid fever. Several types are widely available: typhoid conjugate vaccine (TCV), Ty21a (a live oral vaccine) and Vi capsular polysaccharide vaccine (ViPS) (an injectable subunit vaccine). They are ...

Cholera vaccine Cholera vaccines are vaccines that are effective at preventing cholera. For the first six months after vaccination they provide about 85percent protection, which decreases to 50percent or 62percent during the first year. After two years the leve ...

Plague vaccine Plague vaccine is a vaccine used against ''Yersinia pestis'' to prevent the plague. Inactivated bacterial vaccines have been used since 1890 but are less effective against the pneumonic plague, so live, attenuated vaccines and recombinant protein ...

Pertussis vaccine Pertussis vaccine is a vaccine that protects against whooping cough (pertussis). There are two main types: whole-cell vaccines and acellular vaccines. The whole-cell vaccine is about 78% effective while the acellular vaccine is 71–85% effectiv ...

Advantages and disadvantages

Advantages

* Inactivated pathogens are more stable than live pathogens. Increased stability facilitates the storage and transport of inactivated vaccines. * Unlike live attenuated vaccines, inactivated vaccines cannot revert to a

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 ...

form and cause disease. For example, there have been rare instances of the live attenuated form of poliovirus present in the oral

(OPV) becoming virulent, leading to the inactivated polio vaccine (IPV) replacing OPV in many countries with controlled wild-type polio transmission. *Unlike live attenuated vaccines, inactivated vaccines do not replicate and are not contraindicated for

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 ...

individuals.

Disadvantages

*Inactivated vaccines have a reduced ability to produce a robust immune response for long-lasting immunity when compared to live attenuated vaccines.

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 ...

and boosters are often required to produce and maintain protective immunity. * Pathogens must be cultured and inactivated for the creation of killed whole-organism vaccines. This process slows down vaccine production when compared to genetic vaccines.

References

{{Vaccines