T-dependent immunogens

Fifis T, Gamvrellis A, Crimeen-Irwin B et al (2004) Size-dependent immunogenicity therapeutic and protective properties of nano-vaccines against tumors. J Immunol 173 3148-3154... 

S. pneumoniae has more than 80 sero-types. The current polysaccharide vaccine consists of 23 serotypes and covers about 87% of all pneumococcal diseases in the United States. Current vaccine development is based on conjugate technology and concentrates on the most prevalent 7—9 serotypes. Three multivalent vaccine candidates are in clinical trials. All are based on conjugating the polysaccharide to a T-dependent protein carrier. The results of phase I and II trials in infants have demonstrated the safety and immunogenicity (56—58) of these vaccines. Phase III trials to demonstrate efficacy against systematic diseases and otitis media are in progress and final approval of this vaccine for infant immunization will be by the year 2000. 

Santos, T. Q. and Valdimarsson, H., T-dependent antigens are more immunogenic in the sub-arachnoid space than in other sites, J. Neumimmunol., 2, 215, 1982. 

T-independent immunogens (reviewed by Feldmann, 1974) usually have multiple copies of the same determinant and are, therefore, capable to react with several receptors on the same B cell ( capping ), which activates the cell. At high concentrations, T-independent immunogens may become polyclonal activators of B cells and act as mitogens of B cells. T-dependency may vary with the host haptenated polyacrylamide beads are T-independent in the mouse (Feldmann et al., 1974) and T-dependent in man (Galanaud, 1979). 

North-Holland, Amsterdam Oxford New York Borek F, Stupp Y, Sela M (1965) Immunogenicity and role of size response of guinea pigs to oligotyrosine and tyrosine derivatives. Science 150 1177-1178 Braley-Mullen H (1978) Antigen requirements for induction of B-memory cells. Studies with dinitrophenyl coupled T-dependent and T-independet carriers. J Exp Med 147 1824-1831... 

As described above, most efforts in the development of efficient strategies for presentation of these carbohydrate antigens to the immune system have traditionally relied on the use of a carrier protein, such as KLH, and a potent immunoadjuvant such as QS-21, to enhance the T-cell response. However, more recently, in order to produce substantial levels of both IgM and IgG antibodies capable of reacting with tumor cell lines, increased attention has been drawn to the development of approaches to induce T-cell dependent immunogenic pathways, which either obviate or supplement standard carrier protein-based approaches. 

Yasuda, T., Dancey, G.F., and Kinsky, S.C. (1977) Immunogenicity of liposomal model membranes in mice Dependence on phospholipid composition. Proc. Natl. Acad. Sci. USA 74, 1234-1236. 

Naisbitt, D.J., Fraser Gordon, S., Pirmohamed, M., Burkhart, C., Cribb, A.E., Pichler, W.J., and Kevin Park, B., Antigenicity and immunogenicity of sulphamethoxazole demonstration of metabolism-dependent haptenation and T-cell proliferation in vivo, Br. J. Pharmacol., 133, 295, 2001. 

Immunogenicity can be identified by identifying potential antibodies in plasma. These usually involve ELISA methods. T-cell-dependent antibody responses can be evaluated, and plaque assays involving IgM antibody responses are available. 

The increased cooperation between T cell, B cell, and macrophage also depends on the immunogen and the host. For molecules with low immunogenicity, adjuvants favor the induction of immune response at the expense of tolerance. Extensive reviews on adjuvant action have been presented by Jolles and Paraf (1973), WHO report No. 595 (1973) and Borek (1977). 

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