Further approaches for optimizing polysaccharide-protein conjugate vaccines for prevention of invasive bacterial disease.

The design of conjugate vaccines to optimize their immunologic performance has not been studied extensively. Immunologic performance in relation to changing specific structural parameters in a conjugate can most effectively be analyzed using conjugate syntheses involving terminally activated polysaccharide fragments. Random activation of fragments before conjugation results in more complex and poorly defined conjugates. This is especially true when the length of polysaccharide fragments in polysaccharide-protein conjugates is varied. Both the antigenicity and immunogenicity of saccharide fragments are length-dependent, and antigenicity traditionally has been associated with oligosaccharide epitopes no larger than an antibody site. However, the recent identification of length-stabilized conformational saccharide epitopes has added a new dimension to this concept. The immunologic performance of polysaccharide-protein conjugates is also length-dependent, probably requiring multiple epitopes for optimization.