Comparison of antibody responses induced by a virus-like particle-based vaccine upon intramuscular, pulmonary, and vaginal delivery.

Abstract Virus-like particles (VLPs) can be used as platforms to increase the immunogenicity of antigens that are normally poorly immunogenic, such as self-antigens. We have developed a bacteriophage VLP-based vaccine that targets the HIV coreceptor CCR5 and shown that, following intramuscular administration, it induces high-titer serum antibodies against CCR5 that can inhibit HIV/SIV infection. We have also assessed the ability of this vaccine to induce mucosal immune responses, which is desirable as many pathogens, including HIV, infect at mucosal surfaces. In rats, both intramuscular and pulmonary immunization induced high titer IgG and IgA against the vaccine in the serum, but only the aerosolized vaccine induced CCR5-specific IgA locally in the lung and remotely in the genital tract. We will also present data comparing the magnitude of this "secondary" response in the genital tract to the IgA response invoked following direct immunization of the genital mucosa with different VLP platforms, including VLPs from a virus (human papillomavirus) that normally infects in the genital tract and bacteriophage Qβ VLPs. Our results provide a general method for inducing broad systemic and mucosal antibody responses using VLP-based immunogens.