Enhancement of the immunogenicity and protective efficacy of a mucosal influenza subunit vaccine by the saponin adjuvant GPI-0100

PLoS One. 2012;7(12):e52135. doi: 10.1371/journal.pone.0052135. Epub 2012 Dec 17.

Abstract

Identification of safe and effective adjuvants remains an urgent need for the development of inactivated influenza vaccines for mucosal administration. Here, we used a murine challenge model to evaluate the adjuvant activity of GPI-0100, a saponin-derived adjuvant, on influenza subunit vaccine administered via the intranasal or the intrapulmonary route. Balb/c mice were immunized with 1 µg A/PR/8 (H1N1) subunit antigen alone or in combination with varying doses of GPI-0100. The addition of GPI-0100 was required for induction of mucosal and systemic antibody responses to intranasally administered influenza vaccine and significantly enhanced the immunogenicity of vaccine administered via the intrapulmonary route. Remarkably, GPI-0100-adjuvanted influenza vaccine given at a low dose of 2×1 µg either in the nares or directly into the lungs provided complete protection against homologous influenza virus infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic*
  • Administration, Intranasal
  • Animals
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • Female
  • Immunoglobulin A, Secretory / immunology
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Influenza A Virus, H1N1 Subtype / immunology
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / immunology*
  • Lung / immunology
  • Lung / pathology
  • Lung / virology
  • Mice
  • Mucous Membrane / immunology*
  • Orthomyxoviridae Infections / prevention & control
  • Orthomyxoviridae Infections / virology
  • Saponins / immunology*
  • T-Lymphocytes, Helper-Inducer / immunology
  • Vaccines, Subunit

Substances

  • Adjuvants, Immunologic
  • Antibodies, Viral
  • GPI0100
  • Immunoglobulin A, Secretory
  • Immunoglobulin G
  • Influenza Vaccines
  • Saponins
  • Vaccines, Subunit

Grants and funding

This study was conducted under the auspices of the Netherlands Influenza Vaccine Research Centre (NIVAREC), financially supported by the Netherlands Organisation for Health Research and Development (ZonMw). The study received a subsidy from Jan Kornelis de cock stichting (http://www.decockstichting.nl/subsidies.html). None of the funder had a role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.