Polysaccharide structure dictates mechanism of adaptive immune response to glycoconjugate vaccines

Abstract

Significance Helper T cell responses to glycoconjugate vaccines are regulated through mechanisms dependent upon the structure of the polysaccharide. We show that three of the four important conjugate vaccines tested induced antibody responses regulated primarily by carbohydrate-recognizing helper T cells. However, the adaptive immune response to meningococcal group C (MenC) conjugate was restricted to peptide-recognizing helper T cells. We show that MenC is degraded to a monomeric sialic acid residue that cannot be recognized by T cell receptor as an independent antigen. The structure of the saccharide constitutes a critical factor in determining the processing and presentation of glycoconjugate vaccines. An understanding of the mechanisms underlying the immune responses to glycoconjugates will be crucial in the production of highly protective knowledge-based vaccines.