Antigens reversibly conjugated to a polymeric glyco-adjuvant induce protective humoral and cellular immunity

Fully effective vaccines for complex infections must elicit a diverse repertoire of antibodies (humoral immunity) and CD8+ T-cell responses (cellular immunity). Here, we present a synthetic glyco-adjuvant named p(Man–TLR7), which, when conjugated to antigens, elicits robust humoral and cellular immunity. p(Man–TLR7) is a random copolymer composed of monomers that either target dendritic cells (DCs) via mannose-binding receptors or activate DCs via Toll-like receptor 7 (TLR7). Protein antigens are conjugated to p(Man–TLR7) via a self-immolative linkage that releases chemically unmodified antigen after endocytosis, thus amplifying antigen presentation to T cells. Studies with ovalbumin (OVA)–p(Man–TLR7) conjugates demonstrate that OVA–p(Man–TLR7) generates greater humoral and cellular immunity than OVA conjugated to polymers lacking either mannose targeting or TLR7 ligand. We show significant enhancement of Plasmodium falciparum-derived circumsporozoite protein (CSP)-specific T-cell responses, expansion in the breadth of the αCSP IgG response and increased inhibition of sporozoite invasion into hepatocytes with CSP–p(Man–TLR7) when compared with CSP formulated with MPLA/QS-21-loaded liposomes—the adjuvant used in the most clinically advanced malaria vaccine. We conclude that our antigen–p(Man–TLR7) platform offers a strategy to enhance the immunogenicity of protein subunit vaccines.