Wilson, D. ScottHirosue, SachikoRaczy, Michal M.Bonilla-Ramirez, LeonardoJeanbart, LauraWang, RuyiKwissa, MarcinFranetich, Jean-FrancoisBroggi, Maria A. S.Diaceri, GiacomoQuaglia-Thermes, XavierMazier, DominiqueSwartz, Melody A.Hubbell, Jeffrey A.2019-02-062019-02-062019-02-062019-02-0110.1038/s41563-018-0256-5https://infoscience.epfl.ch/handle/20.500.14299/154373WOS:000456325600020Fully 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 alpha CSP 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.Chemistry, PhysicalMaterials Science, MultidisciplinaryPhysics, AppliedPhysics, Condensed MatterChemistryMaterials SciencePhysicsdendritic cellst-cellsplasmodium-falciparummannose receptorin-vitrovaccinesresponsesantibodydeterminantcytokinesAntigens reversibly conjugated to a polymeric glyco-adjuvant induce protective humoral and cellular immunitytext::journal::journal article::research article