A conjugate vaccine is a type of subunit vaccine which combines a weak

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. ...

with a strong antigen as a carrier so that 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 ...

has a stronger response to the weak antigen.

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 ...

s are used to prevent diseases by invoking an immune response to an antigen, part of a bacterium or virus that the immune system recognizes. This is usually accomplished with an attenuated or dead version of a pathogenic bacterium or virus in the vaccine, so that the immune system can recognize the antigen later in life. Most vaccines contain a single antigen that the body will recognize. However, the antigen of some pathogens does not elicit a strong response from the immune system, so a vaccination against this weak antigen would not protect the person later in life. In this case, a conjugate vaccine is used in order to invoke an immune system response against the weak antigen. In a conjugate vaccine, the weak antigen is covalently attached to a strong antigen, thereby eliciting a stronger immunological response to the weak antigen. Most commonly, the weak antigen is 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 ...

that is attached to strong protein antigen. However,

peptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A ...

/protein and protein/protein conjugates have also been developed.

History

The idea of a conjugate vaccine first appeared in experiments involving rabbits in 1927, when the immune response to the ''Streptococcus pneumoniae'' type 3

antigen was increased by combining the polysaccharide antigen with a protein carrier. The first conjugate vaccine used in humans became available in 1987. This was the ''

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 (Hib) conjugate, which protects against

meningitis Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, headache, and neck stiffness. Other symptoms include confusion or ...

. The vaccine was soon incorporated with the schedule for infant immunization in the United States. The Hib conjugate vaccine is combined with one of several different carrier proteins, such as the

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 the

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 ...

toxoid. Soon after the vaccine was made available the rates of Hib infection dropped, with a decrease of 90.7% between 1987 and 1991. Infection rates diminished even more once the vaccine was made available for infants.

Technique

Vaccines evoke an immune response to an antigen, and the immune system reacts by producing T cells and antibodies. The B memory cells remember the antigen so that if the body encounters it later, antibodies can be produced by B cells to break down the antigen. For bacteria with a polysaccharide coating, the immune response creates

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 ...

s independent of

T cell A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell r ...

stimulation. By conjugating the polysaccharide to a protein carrier, a T cell response can be induced. Normally, polysaccharides by themselves cannot be loaded onto the

major histocompatibility complex The major histocompatibility complex (MHC) is a large locus on vertebrate DNA containing a set of closely linked polymorphic genes that code for cell surface proteins essential for the adaptive immune system. These cell surface proteins are calle ...

(MHC) of

antigen presenting cells 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) because MHC can only bind peptides. In the case of a conjugate vaccine, the carrier peptide linked to the polysaccharide target antigen is able to be presented on the MHC molecule and the T cell can be activated. This improves the vaccine as T cells stimulate a more vigorous immune response and also promote a more rapid and long-lasting immunologic memory. The conjugation of polysaccharide target antigen to the carrier protein also increases efficiency of the vaccine, as a non conjugated vaccine against the polysaccharide antigen is not effective in young children. The immune systems of young children are not able to recognize the antigen as the polysaccharide covering disguises the antigen. By combining the bacterial polysaccharide with another antigen, the immune system is able to respond.

Approved conjugate vaccines

The most commonly used conjugate vaccine is the Hib conjugate vaccine. Other pathogens that are combined in a conjugate vaccine to increase an immune response are ''

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 ...

'' (see

pneumococcal conjugate vaccine Pneumococcal conjugate vaccine is a pneumococcal vaccine and a conjugate vaccine used to protect infants, young children, and adults against disease caused by the bacterium ''Streptococcus pneumoniae'' (pneumococcus). It contains purified capsul ...

) and ''

Neisseria meningitidis ''Neisseria meningitidis'', often referred to as meningococcus, is a Gram-negative bacterium that can cause meningitis and other forms of meningococcal disease such as meningococcemia, a life-threatening sepsis. The bacterium is referred to as a ...

'' (see

meningococcal vaccine Meningococcal vaccine refers to any vaccine used to prevent infection by '' Neisseria meningitidis''. Different versions are effective against some or all of the following types of meningococcus: A, B, C, W-135, and Y. The vaccines are between 8 ...

), both of which are conjugated to protein carriers like those used in the Hib conjugate vaccine. Both ''Streptococcus pneumoniae'' and ''Neisseria meningitidis'' are similar to Hib in that infection can lead to meningitis. In 2018,

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 ...

recommended the use of the

typhoid conjugate vaccine The Vi capsular polysaccharide vaccine (or ViCPS) is a typhoid vaccine recommended by the World Health Organization for the prevention of typhoid (another is Ty21a). The vaccine was first licensed in the US in 1994 and is made from the purified Vi ...

which may be more effective and prevents

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 ...

in many children under the age of five years. In 2021,

Soberana 02 Soberana 02 or Soberana 2, technical name FINLAY-FR-2, is a COVID-19 vaccine produced by the Finlay Institute, a Cuban epidemiological research institute. The vaccine is known as PastoCovac ( fa, پاستوکووک) in Iran, where it has been ...

, a conjugate

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 ...

developed in Cuba, was given emergency use authorisation in Cuba and Iran.

Select list of other conjugate vaccines

* Various

immunocontraception Immunocontraception is the use of an animal's immune system to prevent it from fertilizing offspring. Contraceptives of this type are not currently approved for human use. Typically immunocontraception involves the administration of a vaccine tha ...

vaccines for animal use, including GonaCon (GnRH linked to

keyhole limpet hemocyanin Keyhole limpet hemocyanin (KLH) is a large, multisubunit, oxygen-carrying, metalloprotein that is found in the hemolymph of the giant keyhole limpet, ''Megathura crenulata'', a species of keyhole limpet that lives off the coast of California, fro ...

) *

NicVAX NicVAX is an experimental conjugate vaccine intended to reduce or eliminate physical dependence to nicotine. According to the U.S. National Institute of Drug Abuse, NicVAX can potentially be used to inoculate against nicotine addiction. This pr ...

, which aims to vaccinate against

nicotine Nicotine is a natural product, naturally produced alkaloid in the nightshade family of plants (most predominantly in tobacco and ''Duboisia hopwoodii'') and is widely used recreational drug use, recreationally as a stimulant and anxiolytic. As ...

using a chemically modified

hapten In immunology, haptens are small molecules that elicit an immune response only when attached to a large carrier such as a protein; the carrier may be one that also does not elicit an immune response by itself (in general, only large molecules, i ...

version linked to

exotoxin A The Pseudomonas exotoxin (or exotoxin A) is an exotoxin produced by ''Pseudomonas aeruginosa''. ''Vibrio cholerae'' produces a similar protein called the Cholix toxin (). It inhibits elongation factor-2. It does so by ADP-ribosylation of EF2 u ...

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 t ...

, cocaine linked to inactivated cholera toxin *

TA-NIC TA-NIC is a proprietary vaccine in development similar to TA-CD but being used to create human anti-nicotine antibodies in a person to destroy nicotine in the human body so that it is no longer effective. TA-NIC is a vaccine in development as an ...

, nicotine linked to inactivated cholera toxin

References

External links