a recombinant influenza a virus expressing domain iii of west nile virus induces protective immune responses against influenza and west nile virus甲型流感病毒重组表达域iii的西尼罗河病毒诱发保护性免疫反应对流感和西尼罗河病毒.pdfVIP

A Recombinant Influenza A Virus Expressing Domain III of West Nile Virus Induces Protective Immune Responses against Influenza and West Nile Virus 1 1 1 2 3 Byron E. E. Martina *, Petra van den Doel , Penelope Koraka , Geert van Amerongen , Gunther Spohn , 1 1 1 1 Bart L. Haagmans , Lisette B. V. Provacia , Albert D. M. E. Osterhaus , Guus F. Rimmelzwaan 1 Department of Virology, Erasmus MC, Rotterdam, The Netherlands, 2 The National Institute of Public Health and the Environment, Bilthoven, The Netherlands, 3 Cytos Biotechnology AG, Zurich-Schlieren, Switzerland Abstract West Nile virus (WNV) continues to circulate in the USA and forms a threat to the rest of the Western hemisphere. Since methods for the treatment of WNV infections are not available, there is a need for the development of safe and effective vaccines. Here, we describe the construction of a recombinant influenza virus expressing domain III of the WNV glycoprotein E (Flu-NA-DIII) and its evaluation as a WNV vaccine candidate in a mouse model. FLU-NA-DIII-vaccinated mice were protected from severe body weight loss and mortality caused by WNV infection, whereas control mice succumbed to the infection. In addition, it was shown that one subcutaneous immunization with 105 TCID50 Flu-NA-DIII provided 100% protection against challenge. Adoptive transfer experiments demonstrated that protection was mediated by antibodies and CD4+T cells. Furthermore, mice vaccinated with FLU-NA-DIII developed protective influenza virus-specific antibody titers. It was concluded that this vecto