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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.


Journal article


J Immunol

Publication Date





1030 - 1038


Adaptation, Biological, Amino Acid Sequence, Animals, Cold Temperature, Cross-Priming, Epitopes, Influenza A Virus, H1N1 Subtype, Influenza A Virus, H3N2 Subtype, Mice, Molecular Sequence Data, Nucleoproteins, Orthomyxoviridae Infections, Phylogeny, RNA-Binding Proteins, Survival Rate, T-Lymphocytes, Time Factors, Viral Core Proteins