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Trudeau Institute, Saranac Lake, NY 12983
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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by Grants HL063925 and AI046530 and the Trudeau Institute.
2 T.J.P. and T.S. contributed equally to this work.
3 Present address: J. A. Hollenbaugh, Nova Sterilis, 3109 North Triphammer Road, Lansing, NY 14882.
4 Address correspondence and reprint requests to Dr. Richard W. Dutton, Trudeau Institute 154 Algonquin Avenue, Saranac Lake, NY 12983. E-mail address: dutton{at}northnet.org
5 Abbreviations used in this paper: HA, hemagglutinin; NA, neuraminidase; WT, wild type; EID, 50% egg infectious dose; TCID, 50% tissue culture infectious dose; NP, nuclear protein; PA, acid polymerase.
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