Host- and pathogen-derived adjuvant coatings on protein nanoparticle vaccines

Nanoparticulate and molecular adjuvants have shown great efficacy in enhancing immune responses, and the immunogenic vaccines of the future will most likely contain both. To investigate the immunostimulatory effects of molecular adjuvants on nanoparticle vaccines, we have designed ovalbumin (OVA) protein nanoparticles coated with two different adjuvants-flagellin (FliC) and immunoglobulin M (IgM). These proteins, derived from Salmonella and mice, respectively, are representatives of pathogen- and host-derived molecules that can enhance immune responses. FliC-coated OVA nanoparticles, soluble FliC (sFliC) admixed with OVA nanoparticles, IgM-coated nanoparticles, and OVA-coated nanoparticles were assessed for immunogenicity in an in vivo mouse immunization study. IgM coatings on nanoparticles significantly enhanced both antibody and T cell responses, and promoted IgG2a class switching but not affinity maturation. FliC-coated nanoparticles and FliC-admixed with nanoparticles both triggered IgG2a class switching, but only FliC-coated nanoparticles enhanced antibody affinity maturation. Our findings that affinity maturation and class switching can be directed independently of one another suggest that adjuvant coatings on nanoparticles can be tailored to generate specific vaccine effector responses against different classes of pathogens.