Rational design of conjugate vaccines

Whereas bacterial polysaccharides, classified as T-cell-independent antigens, elicit protective antibodies in adults, booster injections fail to produce an augmented response or promote antibody class switching. Because T-cell-dependent antigens, typically proteins, both produce boosted antibody levels and promote antibody class switching, it has been considered highly desirable to attempt to convert the T-cell-independent polysaccharide antigens into T-cell-dependent antigens, particularly for use in high-risk groups. A number of clinical trials now report the efficacy of conjugate vaccines in inducing the production of antibody in response to a number of previously poorly immunogenic--mainly T-cell-independent--antigens. In addition to conjugate vaccines containing bacterial polysaccharides, vaccines containing relevant peptides from a variety of pathogens are also being formulated and investigated. Questions remain, however, regarding their synthesis, use, and efficacy. The best ages for vaccine administration and selection of the optimal protein carrier are still under investigation, as are questions regarding the use of adjuvants, which can greatly affect the vaccine's potency. Spacing and size of epitope and size and composition of the final structure also must be considered; the importance of molecular size and aggregation of antigen in increasing immunogenicity have been well documented. These questions must be addressed for the much-needed development of conjugate vaccines against some common infections worldwide, including malaria, bacterial meningitis, and infections from Pseudomonas aeruginosa and Neisseria gonorrhoeae because of increasing susceptibility to these infections and resistance of the pathogens to chemotherapeutic agents and/or antibiotics.