Carrier Proteins Facilitate the Generation of Antipolysaccharide Immunity via Multiple Mechanisms

Capsular polysaccharides (CPSs) are important antigenic targets against bacterial infections. As T-independent antigens, however, CPSs elicit short-lived immune responses in adults and are poorly immunogenic in young children. Coupling CPS with protein carriers enhances anti-CPS responses and generates long-lasting immune memory. However, the mechanisms whereby carrier proteins accomplish this are not fully understood. Here, we dissect different mechanisms whereby carrier proteins enhance anti-CPS immunity. We show how coupling CPS with protein carriers modifies the interaction of CPS with antigen-presenting cells, enables a dual-activation mechanism for CPS-specific B cells via interaction with CPS- or carrier-specific T helper cells, and potentiates the recall of anti-CPS responses by engaging memory T helper cells during subsequent vaccination or bacterial exposure. Our findings provide new insights into the immunological basis of carrier-mediated anti-CPS immunity and may help in the design of more effective CPS-based vaccines. IMPORTANCE Polysaccharide capsules, the outermost shells of many bacterial pathogens, play a role in pathogenesis and protect bacteria against the immune system. Generating antipolysaccharide antibodies by vaccination has provided effective protection against infectious diseases caused by encapsulated bacteria. However, most pure polysaccharide preparations are poorly immunogenic, particularly in young children. To circumvent this problem, vaccines have been developed using polysaccharides associated with protein carriers. The precise mechanism whereby protein carriers enhance the immunogenicity of the polysaccharide remains unclear. The significance of our research is in elucidating the different roles played by carriers in facilitating polysaccharide processing and presentation, priming polysaccharide-specific B cells, and potentiating recall antipolysaccharide responses. Overall, our work provides new insights into the immunological basis of carrier-mediated antipolysaccharide immunity and may help in the design of more effective polysaccharide-based vaccines.