Vaccine protection against lethal homologous and heterologous challenge using recombinant AAV vectors expressing codon-optimized genes from pandemic swine origin influenza virus (SOIV)

Vaccine. 2011 Feb 11;29(8):1690-9. doi: 10.1016/j.vaccine.2010.12.037. Epub 2010 Dec 30.

Abstract

The recent H1N1 influenza pandemic and the inevitable delay between identification of the virus and production of the specific vaccine have highlighted the urgent need for new generation influenza vaccines that can preemptively induce broad immunity to different strains of the virus. In this study we have produced AAV-based vectors expressing the A/Mexico/4603/2009 (H1N1) hemagglutinin (HA), nucleocapsid (NP) and the matrix protein M1 and have evaluated their ability to induce specific immune response and protect mice against homologous and heterologous challenge. Each of the vaccine vectors elicited potent cellular and humoral immune responses in mice. Although immunization with AAV-M1 did not improve survival after challenge with the homologous strain, immunization with the AAV-H1 and AAV-NP vectors resulted in survival of all mice, as did inoculation with a combination of all three vectors. Furthermore, trivalent vaccination also conferred partial protection against challenge with the highly heterologous and virulent A/PR/8/34 strain of H1N1 influenza.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Adenoviridae / immunology
  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood
  • Female
  • HEK293 Cells
  • Hemagglutinin Glycoproteins, Influenza Virus / genetics
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology
  • Humans
  • Immunity, Cellular
  • Immunity, Humoral
  • Influenza A Virus, H1N1 Subtype / immunology*
  • Influenza Vaccines / immunology*
  • Interferon-gamma / immunology
  • Mice
  • Mice, Inbred C57BL
  • Neutralization Tests
  • Nucleocapsid Proteins
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / prevention & control*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / immunology
  • Transfection
  • Viral Core Proteins / genetics
  • Viral Core Proteins / immunology
  • Viral Matrix Proteins / genetics
  • Viral Matrix Proteins / immunology
  • Viral Plaque Assay

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Influenza Vaccines
  • M1 protein, Influenza A virus
  • NP protein, Influenza A virus
  • Nucleocapsid Proteins
  • RNA-Binding Proteins
  • Viral Core Proteins
  • Viral Matrix Proteins
  • Interferon-gamma