Heterologous protection against lethal A/HongKong/156/97 (H5N1) influenza virus infection in C57BL/6 mice

The continual threat posed by newly emerging influenza virus strains is dem onstrated by the recent outbreak of H5N1 influenza virus in Hong Kong, Curr ently, immunization against influenza virus infection is fairly adequate, b ut it is imperative that improved vaccines are developed that can protect a gainst a variety of strains and be generated rapidly. Since humoral immunit y is ineffective against serologically distinct viruses, one strategy would be to develop vaccines that emphasize cellular immunity. Here we report th e successful protection of C57BL/6 mice from a lethal A/HK/156/97 (HK156) i nfection by immunizing first with an H9N2 isolate, A/Quail/HK/G1/97 (QHKG1) , that harbours internal genes 98% homologous to HK156, This strategy also protected mice that are deficient in antibody production, indicating that t he immunity is T-cell-mediated. In the course of these studies, we generate d a highly pathogenic H5N1 reassortant which implicated NP and PB2 as havin g an important contribution to pathogenesis when present with a highly clea vable H5. These results provide the first demonstration that protective cel l-mediated immunity can be established against the highly virulent HK156 vi rus and have important implications for the development of novel strategies for the prevention and treatment of HK156 infection and the design of futu re influenza vaccines.