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.