Abstract

The emergence of severe cases of human influenza A (H7N9) viral infection in China in the spring of 2003 resulted in a global effort to rapidly develop an effective candidate vaccine. In this study, a cold-adapted (ca), live attenuated monovalent reassortant influenza H7N9 virus (Ah01/AA ca) was generated using reverse genetics that contained hemagglutinin (HA) and neuraminidase (NA) genes from a 2013 pandemic A H7N9 isolate, A/Anhui/01/2013 virus (Ah01/H7N9); the remaining six backbone genes derived from the cold-adapted influenza H2N2 A/Ann Arbor/6/60 virus (AA virus). Ah01/AA ca virus exhibited temperature sensitivity (ts), ca, and attenuation (att) phenotypes. Intranasal immunization of female BALB/c mice with Ah01/AA ca twice at a 2-week interval induced robust humoral, mucosal, and cell-mediated immune responses in a dose-dependent manner. Furthermore, the candidate Ah01/AA ca virus was immunogenic and offered partial or complete protection of mice against a lethal challenge by the live 2013 influenza A H7N9 (A/Anhui/01/2013). Protection was demonstrated by the inhibition of viral replication and the attenuation of histopathological changes in the challenged mouse lung. Taken together, these data support the further evaluation of this Ah01/AA ca candidate vaccine in primates.

Highlights

  • Since the first notification at the end of March 2013, China has been reporting cases of human infection with H7N9 virus to the World Health Organization

  • Three cold-adapted influenza A virus strains, A/Ann Arbor/6/60 (AA) (H2N2), A/ Leningrad/134/17/57 (H2N2), and A/Leningrad/134/47/57 (H2N2), and two B virus strains, B/ Ann Arbor/1/66 ca and B/USSR/60/69 ca have been developed as a live attenuated influenza vaccine (LAIV) Master Donor virus to generate seasonal influenza vaccines for clinical use in humans [7,8,9] We reported previously a successful rescue of ca, ts and att reassortant influenza A H1N1 viruses in a short period of time using reverse genetic technology

  • The reassortant Ah01/AA ca viruses were produced through the use of reverse genetics

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Summary

Introduction

Since the first notification at the end of March 2013, China has been reporting cases of human infection with H7N9 virus to the World Health Organization. This outbreak was the first identification of infection with this virus in humans [1,2,3]. As of June 2014, a total of 450 laboratory-confirmed cases of human infection with the avian influenza A (H7N9) virus, resulting in 165 deaths, have been identified and reported to the WHO. The Chinese National Health and Family Planning Commission reported 435 of these cases. To date, this virus does not appear. PLOS ONE | DOI:10.1371/journal.pone.0123659 April 17, 2015

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