Conjugate vaccine

A conjugate vaccine is created by covalently attaching a poor antigen to a carrier protein, 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.

The immune response
During immune recognition of foreign molecules, the external environment is sampled by pre-B cells which have surface receptors that bind foreign molecules, internalize and proteolytically digest them. Some of the resulting peptide fragments (T cell epitopes) are reexpressed on the cell surface in association with MHC II molecules. This "loaded" MHC II may be recognized by complementary T cells that are then stimulated to release cytokines. The cytokines stimulate the pre-B cell to do a number of exciting 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 alternate stimulation can still occur if the antigen has a repeating structure (i.e. polysaccharide), but because of the lack of T cell help polysaccharides are poor vaccines that do not produce an anamnestic response. They are "T-independent antigens". Toddlers are unable to respond to T-independent antigens, yet have lost their maternal antibodies, so they are particularly susceptible to infection by encapsulated bacteria.

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.