Influenza Virus-Like Particles Containing M2 Induce Broadly Cross Protective Immunity

PLoS One. 2011 Jan 18;6(1):e14538. doi: 10.1371/journal.pone.0014538.

Abstract

Background: Current influenza vaccines based on the hemagglutinin protein are strain specific and do not provide good protection against drifted viruses or emergence of new pandemic strains. An influenza vaccine that can confer cross-protection against antigenically different influenza A strains is highly desirable for improving public health.

Methodology/principal findings: To develop a cross protective vaccine, we generated influenza virus-like particles containing the highly conserved M2 protein in a membrane-anchored form (M2 VLPs), and investigated their immunogenicity and breadth of cross protection. Immunization of mice with M2 VLPs induced anti-M2 antibodies binding to virions of various strains, M2 specific T cell responses, and conferred long-lasting cross protection against heterologous and heterosubtypic influenza viruses. M2 immune sera were found to play an important role in providing cross protection against heterosubtypic virus and an antigenically distinct 2009 pandemic H1N1 virus, and depletion of dendritic and macrophage cells abolished this cross protection, providing new insight into cross-protective immune mechanisms.

Conclusions/significance: These results suggest that presenting M2 on VLPs in a membrane-anchored form is a promising approach for developing broadly cross protective influenza vaccines.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral
  • Cross Protection / immunology*
  • Dendritic Cells / virology
  • Humans
  • Immunity
  • Influenza A Virus, H1N1 Subtype / immunology*
  • Influenza A virus / immunology*
  • Influenza Vaccines / immunology*
  • Macrophages / virology
  • Mice
  • Orthomyxoviridae Infections
  • Viral Matrix Proteins / immunology*
  • Virion / immunology*

Substances

  • Antibodies, Viral
  • Influenza Vaccines
  • M2 protein, Influenza A virus
  • Viral Matrix Proteins