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Development of a new candidate H5N1 avian influenza virus for pre‐pandemic vaccine production
Authors:Jie Dong  Yumiko Matsuoka  Taronna R. Maines  David E. Swayne  Eduardo O’Neill  C. Todd Davis  Neal Van‐Hoven  Amanda Balish  Hong‐jie Yu  Jacqueline M. Katz  Alexander Klimov  Nancy Cox  De‐xin Li  Yu Wang  Yuan‐ji Guo  Wei‐zhong Yang  Ruben O. Donis  Yue‐long Shu
Affiliation:1. Chinese National Influenza Center, State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, China CDC, Xuanwu District Beijing, China;2. Influenza Division, Centers for Disease Control and Prevention, Atlanta, GA, USA;3. Southeast Poultry Research Laboratory, Agricultural Research Service, United States Department of Agriculture, Athens, GA, USA
Abstract:
Background Highly pathogenic H5N1 avian influenza viruses currently circulating in birds have caused hundreds of human infections, and pose a significant pandemic threat. Vaccines are a major component of the public health preparedness for this likely event. The rapid evolution of H5N1 viruses has resulted in the emergence of multiple clades with distinct antigenic characteristics that require clade‐specific vaccines. A variant H5N1 virus termed clade 2.3.4 emerged in 2005 and has caused multiple fatal infections. Vaccine candidates that match the antigenic properties of variant viruses are necessary because inactivated influenza vaccines elicit strain‐specific protection. Objective To address the need for a suitable seed for manufacturing a clade 2.3.4 vaccine, we developed a new H5N1 pre‐pandemic candidate vaccine by reverse genetics and evaluated its safety and replication in vitro and in vivo. Methods A reassortant virus termed, Anhui/PR8, was produced by reverse genetics in compliance with WHO pandemic vaccine development guidelines and contains six genes from A/Puerto Rico/8/34 as well as the neuraminidase and hemagglutinin (HA) genomic segments from the A/Anhui/01/2005 virus. The multi‐basic cleavage site of HA was removed to reduce virulence. Results The reassortant Anhui/PR8 grows well in eggs and is avirulent to chicken and ferrets but retains the antigenicity of the parental A/Anhui/01/2005 virus. Conclusion These results indicate that the Anhui/PR8 reassortant lost a major virulent determinant and it is suitable for its use in vaccine manufacturing and as a reference vaccine virus against the H5N1 clade 2.3.4 viruses circulating in eastern China, Vietnam, Thailand, and Laos.
Keywords:Pandemic influenza  H5N1 vaccine  seed virus
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