Poly-γ-glutamic acid/chitosan nanogel greatly enhances the efficacy and heterosubtypic cross-reactivity of H1N1 pandemic influenza vaccine

Sci Rep. 2017 Mar 21:7:44839. doi: 10.1038/srep44839.

Abstract

In 2009, the global outbreak of an influenza pandemic emphasized the need for an effective vaccine adjuvant. In this study, we examined the efficacy of poly-γ-glutamic acid/chitosan (PC) nanogel as an adjuvant for the influenza vaccine. PC nanogel significantly enhanced antigen-specific cross-presentation and cytotoxic T lymphocyte (CTL) activity. Compared with alum, the protective efficacy of the pandemic H1N1 influenza (pH1N1) vaccine was substantially increased by PC nanogel, with increased hemagglutination-inhibition titers, CTL activity, and earlier virus clearance after homologous and heterosubtypic [A/Philippines/2/82 (H3N2)] virus challenges. However, CD8+ T cell-depleted mice displayed no protection against the heterosubtypic virus challenge after immunization with PC nanogel-adjuvanted pH1N1 vaccine. We also observed that using PC nanogel as a vaccine adjuvant had a dose-sparing effect and significantly enhanced the long-lasting protection of the pH1N1 vaccine. Together, these results suggest that PC nanogel is a promising vaccine adjuvant that could broadly prevent influenza virus infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic
  • Animals
  • Antigen Presentation / immunology
  • Antigens, Viral / immunology
  • Chitosan / analogs & derivatives*
  • Chitosan / chemistry
  • Cross Reactions / immunology*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Disease Models, Animal
  • Ferrets
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Immunity, Cellular
  • Immunogenicity, Vaccine*
  • Influenza A Virus, H1N1 Subtype / immunology*
  • Influenza Vaccines / chemistry
  • Influenza Vaccines / immunology*
  • Influenza, Human / prevention & control*
  • Mice
  • Orthomyxoviridae Infections / mortality
  • Orthomyxoviridae Infections / prevention & control
  • Phagosomes / metabolism
  • Polyglutamic Acid / analogs & derivatives*
  • Polyglutamic Acid / chemistry

Substances

  • Adjuvants, Immunologic
  • Antigens, Viral
  • Histocompatibility Antigens Class I
  • Influenza Vaccines
  • chitosan-poly(gamma-glutamic acid)
  • Polyglutamic Acid
  • Chitosan