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

被引:119
作者
Powell, Timothy J. [1 ]
Strutt, Tara [1 ]
Reome, Joyce [1 ]
Hollenbaugh, Joseph A. [1 ]
Roberts, Alan D. [1 ]
Woodland, David L. [1 ]
Swain, Susan L. [1 ]
Dutton, Richard W. [1 ]
机构
[1] Trudeau Inst Inc, Saranac Lake, NY 12983 USA
关键词
D O I
10.4049/jimmunol.178.2.1030
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:1030 / 1038
页数:9
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