The Complex of Poly-γ-Glutamic Acid and Alum Induces Cross-Protective Immunity of Pandemic H1N1 Influenza Vaccine

Abstract Vaccination is the most effective strategy to protect against infectious diseases, and adjuvants are key vaccine components that improve antigen-specific immune responses. Here, we developed a new adjuvant named PGA/Alum by combining poly-γ-glutamic acid (γ-PGA) with alum and investigated its ability to enhance the immunogenicity and the cross-reactive efficacy of pandemic H1N1 (pH1N1) influenza vaccine antigen. PGA/Alum highly induced in vitro activation and antigen processing of dendritic cells, and enhanced antigen delivery to draining lymph nodes and antigen-specific immunogenicity in mice using OVA as a model antigen. Also, OVA-specific antibody production, cytotoxic T lymphocyte (CTL) activity, and antibody-dependent cellular cytotoxicity (ADCC) were greatly increased by PGA/Alum. These abilities of PGA/Alum improved the protective efficacy of pH1N1 vaccine antigen by increasing hemagglutination-inhibition titers, enhancing ADCC and CTL activity, and speeding viral clearance following homologous viral challenge. Importantly, PGA/Alum significantly enhanced the cross-protective efficacy of pH1N1 vaccine against heterologous viruses [A/Puerto Rico/8/34 (H1N1) and A/Hong Kong/1/1968 (H3N2)] by inducing cross-reactive ADCC and CTL activities. Together, our results strongly suggest that PGA/Alum may be a promising vaccine adjuvant for preventing influenza and other infectious diseases.