Development of a Universal Influenza A Vaccine Based on the M2e Peptide Fused to the Papaya Mosaic Virus (PapMV) Vaccine Platform

Vaccine. 2008 Jun 25;26(27-28):3395-403. doi: 10.1016/j.vaccine.2008.04.052. Epub 2008 May 12.

Abstract

With the emergence of highly virulent influenza viruses and the consequent risk of pandemics, new approaches to designing universal influenza vaccines are urgently needed. In this report, we demonstrate the potential of using a papaya mosaic virus (PapMV) platform carrying the universal M2e influenza epitope (PapMV-CP-M2e) as a candidate flu vaccine. We show that PapMV-CP-M2e virus-like particles (VLPs) can induce production in mice of anti-M2e antibodies that can recognize influenza-infected cells. PapMV-CP-M2e discs made of 20 coat protein (CP) subunits were shown to be poorly immunogenic compared to PapMV-CP-M2e VLPs composed of several hundred CP subunits. We also show that addition of either alum or PapMV-CP VLPs as adjuvant dramatically increased the immunogenicity of PapMV-CP-M2e-containing vaccine, and led to 100% protection against a challenge of 4LD(50) with the WSN/33 strain. These results show, for the first time, the potential of a recombinant plant virus protein to serve as both peptide delivery system and adjuvant in the crucial field of influenza vaccine development.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Alum Compounds / administration & dosage
  • Alum Compounds / pharmacology
  • Animals
  • Antibodies, Viral
  • Genetic Vectors
  • Influenza Vaccines / genetics
  • Influenza Vaccines / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Orthomyxoviridae Infections / prevention & control
  • Potexvirus / genetics*
  • Survival Analysis
  • Viral Matrix Proteins / genetics
  • Viral Matrix Proteins / immunology*
  • Virosomes / administration & dosage
  • Virosomes / pharmacology

Substances

  • Adjuvants, Immunologic
  • Alum Compounds
  • Antibodies, Viral
  • Influenza Vaccines
  • M2 protein, Influenza A virus
  • Viral Matrix Proteins
  • Virosomes
  • aluminum sulfate