Abstract
Protection against encapsulated bacteria can be elicited using polysaccharide vaccines. These antigens often behave as T-cell-independent type 2 antigens (TI-2 Ags). However, TI-2 Ags, including pneumococcal polysaccharides, often elicit weak immunoglobulin G (IgG) responses and are refractive to boosting. Conjugate vaccines have not completely overcome this challenge and hence, alternative strategies are required to enhance polysaccharide vaccine responses. Herein, we describe an adjuvant consisting of a Toll-like receptor and C-type lectin receptor agonist pairing that significantly increases primary immunoglobulin M and IgG responses to TI-2 Ags as well as enables significant boosting when coadministered with polysaccharide vaccines. Consistent with this, the adjuvant significantly increased the generation of both TI-2 memory B cells and long-lived antibody secreting cells. Adjuvant effects were highly dependent on B-cell-intrinsic MyD88, but not Trif expression. Importantly, coadministration of the adjuvant with the Pneumovax vaccine significantly increased the protective efficacy of vaccination in a lethal challenge mouse model of pneumococcal respiratory infection. Collectively, these data provide evidence that B-cell-directed adjuvants have promise in significantly improving the quality and quantity of serologic and B-cell memory responses to clinically relevant polysaccharide vaccines.