Poly-γ-Glutamic Acid Complexed With Alum Induces Cross-Protective Immunity of Pandemic H1N1 Vaccine

Front Immunol. 2019 Jul 11:10:1604. doi: 10.3389/fimmu.2019.01604. eCollection 2019.

Abstract

The use of a good vaccine adjuvant may induce a higher immunogenicity profile of vaccine antigens. Here, we developed a new adjuvant by combining poly-γ-glutamic acid (γ-PGA) with alum (PGA/Alum) and investigated its ability to enhance the immunogenicity and the cross-reactive efficacy of pandemic H1N1 (pH1N1) influenza vaccine antigen. PGA/Alum enhanced antigen delivery to draining lymph nodes and antigen-specific immunogenicity in mice using OVA as a model antigen. It also greatly increased OVA-specific antibody production, cytotoxic T lymphocyte (CTL) activity, and antibody-dependent cellular cytotoxicity (ADCC). 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, the cross-protective efficacy of pH1N1 vaccine against heterologous viruses [A/Puerto Rico/8/34 (H1N1) and A/Hong Kong/1/1968 (H3N2)] was significantly enhanced by PGA/Alum, and cross-reactive ADCC and CTL activities were observed. Together, our results strongly suggest that PGA/Alum may be a promising vaccine adjuvant for preventing influenza and other infectious diseases.

Keywords: antibody-dependent cellular cytotoxicity; cross-protection; cytotoxic T lymphocyte activity; efficacy; influenza virus; vaccine adjuvant.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic*
  • Alum Compounds*
  • Animals
  • Antibodies, Viral / immunology
  • Antibody-Dependent Cell Cytotoxicity / immunology
  • Antigen Presentation / immunology
  • Cell Survival
  • Cross Reactions / immunology*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Disease Models, Animal
  • Humans
  • Immunity, Cellular
  • Immunity, Humoral
  • Immunization
  • Influenza A Virus, H1N1 Subtype / immunology*
  • Influenza Vaccines / immunology*
  • Influenza, Human / immunology
  • Influenza, Human / prevention & control
  • Lymph Nodes / immunology
  • Lymph Nodes / metabolism
  • Lymph Nodes / pathology
  • Mice
  • Orthomyxoviridae Infections / immunology*
  • Orthomyxoviridae Infections / prevention & control
  • Polyglutamic Acid / analogs & derivatives*
  • Polyglutamic Acid / immunology

Substances

  • Adjuvants, Immunologic
  • Alum Compounds
  • Antibodies, Viral
  • Influenza Vaccines
  • poly(gamma-glutamic acid)
  • Polyglutamic Acid
  • aluminum sulfate