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

antigen In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, 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 systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to bacteria, as well as Tumor immunology, cancer cells, Parasitic worm, parasitic ...

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 verifi ...

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 wat ...

that is attached to strong protein antigen. However,

peptide Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Da or more are called proteins. Chains of fewer than twenty am ...

/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, Motility, non-motile, Coccobacillus, coccobacillary, facultative anaerobic organism, facultatively anaerobic, Capnophile, capnophili ...

'' 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, intense headache, vomiting and neck stiffness and occasion ...

. 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 bacteria, bacterium ''Corynebacterium diphtheriae''. Most infections are asymptomatic or have a mild Course (medicine), clinical course, but in some outbreaks, the mortality rate approaches 10%. Signs a ...

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 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 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 inserted into the plasm ...

s independent of

T cell T cells (also known as T lymphocytes) are an important part 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 receptor (TCR) on their cell ...

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 (genetics), locus on vertebrate DNA containing a set of closely linked polymorphic genes that code for Cell (biology), cell surface proteins essential for the adaptive immune system. The ...

(MHC) of antigen presenting cells (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'' (see pneumococcal conjugate vaccine) and '' Neisseria meningitidis'' (see meningococcal vaccine), 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 list of specialized agencies of the United Nations, specialized agency of the United Nations which coordinates responses to international public health issues and emergencies. It is headquartered in Gen ...

recommended the use of the typhoid conjugate vaccine which may be more effective and prevents typhoid fever in many children under the age of five years. In 2021, Soberana 02, a conjugate COVID-19 vaccine developed in Cuba, was given emergency use authorisation in Cuba and Iran.

Select list of other conjugate vaccines

* Various immunocontraception vaccines for animal use, including GonaCon (GnRH linked to keyhole limpet hemocyanin) * NicVAX, which aims to vaccinate against nicotine using a chemically modified hapten version linked to exotoxin A * TA-CD, cocaine linked to inactivated cholera toxin * TA-NIC, nicotine linked to inactivated cholera toxin

References

External links