HIV-1 and influenza antigens synthetically linked to IgG2a Fc elicit superior humoral responses compared to unmodified antigens in mice

Using murine IgG subclass molecules (IgG1 or IgG2a) synthetically fused to HIV-1 or influenza test antigens, we explored the potential for IgG Fc scaffolds to augment immunogenicity. Each antigen (Ag) was grafted onto a hinge-Fc scaffold containing all critical residues necessary for interaction with effector cells, thus retaining effector functions of the native IgG subclass. We hypothesized that the differential affinity of FcγRs for specific IgG subclasses would influence the magnitude of immune responses elicited by immunization with an Ag-IgG Fc fusion vaccine. We demonstrate here that the antigen-specific humoral response elicited by Ag-IgG2a fusion vaccines is at least tenfold greater than that elicited by native antigen, that this response is superior to that elicited by Ag-IgG1, and that the augmented antigen-specific humoral response elicited is Fcγ receptor-dependent.

► Influenza hemagglutinin and HIV envelope antigens fused to IgG2a Fc are highly immunogenic.
► Antigen-IgG2a fusion vaccines elicit superior humoral responses relative to native antigens.
► Antigen-IgG2a fusion vaccine potency is Fcγ receptor-dependent.