Infection of Influenza Virus Neuraminidase-Vaccinated Mice With Homologous Influenza Virus Leads to Strong Protection Against Heterologous Influenza Viruses

J Gen Virol. 2014 Dec;95(Pt 12):2627-2637. doi: 10.1099/vir.0.067736-0. Epub 2014 Aug 28.


Vaccination is the best measure to prevent influenza pandemics. Here, we studied the protective effect against heterologous influenza viruses, including A/reassortant/NYMC X-179A (pH1N1), A/Chicken/Henan/12/2004 (H5N1), A/Chicken/Jiangsu/7/2002 (H9N2) and A/Guizhou/54/89×A/PR/8/34 (A/Guizhou-X) (H3N2), in mice first vaccinated with a DNA vaccine of haemagglutinin (HA) or neuraminidase (NA) of A/PR/8/34 (PR8) and then infected with the homologous virus. We showed that PR8 HA or NA vaccination both protected mice against a lethal dose of the homologous virus; PR8 HA or NA DNA vaccination and then PR8 infection in mice offered poor or excellent protection, respectively, against a second, heterologous influenza virus challenge. In addition, before the second heterologous influenza infection, the highest antibody level against nucleoprotein (NP) and matrix (M1 and M2) proteins was found in the PR8 NA-vaccinated and PR8-infected group. The level of induced cellular immunity against NP and M1 showed a trend consistent with that seen in antibody levels. However, PR8 HA+NA vaccination and then PR8 infection resulted in limited protection against heterologous influenza virus challenge. Results of the present study demonstrated that infection of the homologous influenza virus in mice already immunized with a NA vaccine could provide excellent protection against subsequent infection of a heterologous influenza virus. These findings suggested that NA, a major antigen of influenza virus, could be an important candidate antigen for universal influenza vaccines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral
  • Female
  • Immunity, Humoral
  • Influenza A virus / classification*
  • Influenza A virus / genetics
  • Influenza Vaccines / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Neuraminidase / immunology*
  • Orthomyxoviridae / classification*
  • Orthomyxoviridae / enzymology
  • Orthomyxoviridae / immunology
  • Orthomyxoviridae Infections / prevention & control*
  • Orthomyxoviridae Infections / virology
  • Reassortant Viruses
  • Specific Pathogen-Free Organisms
  • Vaccines, DNA / immunology
  • Viral Load


  • Antibodies, Viral
  • Influenza Vaccines
  • Vaccines, DNA
  • Neuraminidase