Priming with cold-adapted influenza A does not prevent infection but elicits long-lived protection against supralethal challenge with heterosubtypic virus

J Immunol. 2007 Jan 15;178(2):1030-8. doi: 10.4049/jimmunol.178.2.1030.

Abstract

We show in this study several novel features of T cell-based heterosubtypic immunity against the influenza A virus in mice. First, T cell-mediated heterosubtypic protection against lethal challenge can be generated by a very low priming dose. Second, it becomes effective within 5-6 days. Third, it provides protection against a very high dose challenge for >70 days. Also novel is the finding that strong, long-lasting, heterosubtypic protection can be elicited by priming with attenuated cold-adapted strains. We demonstrate that priming does not prevent infection of the lungs following challenge, but leads to earlier clearance of the virus and 100% survival after otherwise lethal challenge. Protection is dependent on CD8 T cells, and we show that CD4 and CD8 T cells reactive to conserved epitopes of the core proteins of the challenge virus are present after priming. Our results suggest that intranasal vaccination with cold-adapted, attenuated live virus has the potential to provide effective emergency protection against emerging influenza strains for several months.

Publication types

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

MeSH terms

  • Adaptation, Biological*
  • Amino Acid Sequence
  • Animals
  • Cold Temperature*
  • Cross-Priming / immunology*
  • Epitopes / chemistry
  • Epitopes / immunology
  • Influenza A Virus, H1N1 Subtype / classification
  • Influenza A Virus, H1N1 Subtype / physiology*
  • Influenza A Virus, H3N2 Subtype / classification
  • Influenza A Virus, H3N2 Subtype / physiology*
  • Mice
  • Molecular Sequence Data
  • Nucleocapsid Proteins
  • Nucleoproteins / chemistry
  • Nucleoproteins / immunology
  • Orthomyxoviridae Infections / immunology*
  • Orthomyxoviridae Infections / prevention & control
  • Orthomyxoviridae Infections / virology*
  • Phylogeny
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / immunology
  • Survival Rate
  • T-Lymphocytes / immunology
  • Time Factors
  • Viral Core Proteins / chemistry
  • Viral Core Proteins / immunology

Substances

  • Epitopes
  • NP protein, Influenza A virus
  • Nucleocapsid Proteins
  • Nucleoproteins
  • RNA-Binding Proteins
  • Viral Core Proteins