Conjugate vaccine
Encyclopedia
A conjugate vaccine is created by covalently attaching a poor (polysaccharide organism) antigen
to a carrier protein
(preferably from the same microorganism), thereby conferring the immunological attributes of the carrier on the attached antigen. This technique for the creation of an effective immunogen is most often applied to bacterial polysaccharides
for the prevention of invasive bacterial disease.
. This "loaded" MHC II may be recognized by complementary T cell
s that are then stimulated to release cytokine
s. The cytokines stimulate the pre-B cell to do a number of different things. The cell will mature to an antibody
-secreting B cell, replicate itself to an enormous extent, follow a maturation pathway that results in improvement of the antibody structure and production of long lived memory B cells. Maturation is responsible for two hallmarks of the immune response: the production of high affinity antibodies and the creation of memory of prior exposure (anamnestic response). Because the immune response is aided by T cells, proteins are "T-dependent antigens".
If the foreign molecule is not a protein, then proteolyic digestion can not occur and the T-dependent pathway described above does not operate. An antigen-specific antibody response can still occur if the antigen has a repetitive structure (i.e. polysaccharide) or is arranged in a repetitive manner (i.e. proteins arranged on a viral capsid) leading these to be called T-independent antigens. Young children have been shown to be unresponsive to T-independent antigens, leaving them particularly susceptible to infection by encapsulated bacteria and certain viral pathogens.
It was recognized early in the 20th century that attaching a hapten
to a carrier protein made the hapten immunogenic
. This was extended in the work of Harold Jennings, John Robbins and others to polysaccharides. Polysaccharide conjugates bind to polysaccharide-specific pre-B cells and are taken up. Once inside the cell, the protein portion is digested to release T cell epitopes that result in T cell help. The polysaccharide is converted to a T-dependent antigen by the simultaneous presence of the carrier protein.
This technique has allowed the production of several commercially and medically important vaccines (various capsule types of H. influenza, N. meningitidis and S. pneumoniae), as well as numerous experimental vaccines.
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
to a carrier protein
Carrier protein
Carrier proteins are proteins involved in the movement of ions, small molecules, or macromolecules, such as another protein, across a biological membrane. Carrier proteins are integral membrane proteins; that is they exist within and span the membrane across which they transport substances. The...
(preferably from the same microorganism), thereby conferring the immunological attributes of the carrier on the attached antigen. This technique for the creation of an effective immunogen is most often applied to bacterial polysaccharides
Polysaccharide
Polysaccharides are long carbohydrate molecules, of repeated monomer units joined together by glycosidic bonds. They range in structure from linear to highly branched. Polysaccharides are often quite heterogeneous, containing slight modifications of the repeating unit. Depending on the structure,...
for the prevention of invasive bacterial disease.
The immune response
During immune recognition of foreign molecules, the external environment is sampled by naive B cells and dendritic cells which have surface receptors that internalize proteins leading to proteolytic digestion. Some of the resulting peptide fragments (T cell epitopes) are reexpressed on the cell surface in association with MHC II moleculesMHC class II
MHC Class II molecules are found only on a few specialized cell types, including macrophages, dendritic cells and B cells, all of which are professional antigen-presenting cells ....
. This "loaded" MHC II may be recognized by complementary T cell
T cell
T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...
s that are then stimulated to release cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
s. The cytokines stimulate the pre-B cell to do a number of different things. The cell will mature to an antibody
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
-secreting B cell, replicate itself to an enormous extent, follow a maturation pathway that results in improvement of the antibody structure and production of long lived memory B cells. Maturation is responsible for two hallmarks of the immune response: the production of high affinity antibodies and the creation of memory of prior exposure (anamnestic response). Because the immune response is aided by T cells, proteins are "T-dependent antigens".
If the foreign molecule is not a protein, then proteolyic digestion can not occur and the T-dependent pathway described above does not operate. An antigen-specific antibody response can still occur if the antigen has a repetitive structure (i.e. polysaccharide) or is arranged in a repetitive manner (i.e. proteins arranged on a viral capsid) leading these to be called T-independent antigens. Young children have been shown to be unresponsive to T-independent antigens, leaving them particularly susceptible to infection by encapsulated bacteria and certain viral pathogens.
It was recognized early in the 20th century that attaching a hapten
Hapten
A hapten is a small molecule that can 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...
to a carrier protein made the hapten immunogenic
Immunogenicity
Immunogenicity is the ability of a particular substance, such as an antigen or epitope, to provoke an immune response in the body of a human or animal.- Immunogenicity :The ability to induce humoral and/or cell-mediated immune responses....
. This was extended in the work of Harold Jennings, John Robbins and others to polysaccharides. Polysaccharide conjugates bind to polysaccharide-specific pre-B cells and are taken up. Once inside the cell, the protein portion is digested to release T cell epitopes that result in T cell help. The polysaccharide is converted to a T-dependent antigen by the simultaneous presence of the carrier protein.
This technique has allowed the production of several commercially and medically important vaccines (various capsule types of H. influenza, N. meningitidis and S. pneumoniae), as well as numerous experimental vaccines.
See also
- Haemophilus influenzae type b (Hib)Haemophilus influenzaeHaemophilus influenzae, formerly called Pfeiffer's bacillus or Bacillus influenzae, Gram-negative, rod-shaped bacterium first described in 1892 by Richard Pfeiffer during an influenza pandemic. A member of the Pasteurellaceae family, it is generally aerobic, but can grow as a facultative anaerobe. H...
- Hib vaccineHib vaccineHaemophilus influenzae type B vaccine is a conjugate vaccine developed for the prevention of invasive disease caused by Haemophilus influenzae type b bacteria. The Centers for Disease Control and Prevention has recommended the use of the Hib vaccine. Due to routine use of the Hib vaccine in...
- Meningococcal vaccineMeningococcal vaccineMeningococcal vaccine is a vaccine used against Meningococcus, a bacterium that causes meningitis, meningococcemia, septicemia, and rarely carditis, septic arthritis, or pneumonia.-Types:...
- Pneumococcal vaccinesPneumococcal polysaccharide vaccinePneumococcal polysaccharide vaccine — the latest version is known as Pneumovax 23 — is the first pneumococcal vaccine, the first vaccine derived from a capsular polysaccharide, and an important landmark in medical history...
- ImmunogenicityImmunogenicityImmunogenicity is the ability of a particular substance, such as an antigen or epitope, to provoke an immune response in the body of a human or animal.- Immunogenicity :The ability to induce humoral and/or cell-mediated immune responses....
- B cellB cellB cells are lymphocytes that play a large role in the humoral immune response . The principal functions of B cells are to make antibodies against antigens, perform the role of antigen-presenting cells and eventually develop into memory B cells after activation by antigen interaction...
External links
- http://nichddirsage.nichd.nih.gov:8080/ar2004/pages/ldmi/biot.htm
- http://www.nrc-cnrc.gc.ca/education/sti-1990s_jennings_e.html