Design And Development Of Glycoconjugate Vaccines

An optimal glyconjugate vaccine stimulates a potent and specific immune response to a saccharide antigen, while irreversibly bound to the carrier protein. In order to elicit a robust and potent immune response, it is important that the critical immunogenic epitopes in the saccharide antigen, are preserved. In addition, the overall conjugate structure should be of an optimal size and the carrier protein T-cell epitopes are also largely preserved. As a result of the need to maintain these functional and structural requirements, several key elements need to be considered during the design and development of conjugate vaccines. These elements include (a) preservation of critical immunogenic saccharide epitopes, including the key non-saccharide substituents; length; (b) minimal antigen modification; (c) optimal chain (d) efficient conjugation chemistry; (e) selection of an effective and well tolerated carrier protein; and (f) stability of the conjugate in the drug substance as well as drug product. In this chapter, we review the key design features necessary to develop the "optimal conjugate vaccine construct" and the "toolbox" to achieve these ends.