|DAVIS, C. TODD|
Submitted to: Influenza and Other Respiratory Viruses
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/19/2009
Publication Date: 10/9/2009
Citation: Dong, J., Matsuoka, Y., Maines, T.R., Swayne, D.E., O'Neill, E., Davis, C., Van-Hoven, N., Balish, A., Yu, H., Katz, J.M., Klimov, A., Cox, N., Li, D., Wang, Y., Guo, Y., Yang, W., Donis, R.O., Shu, Y. 2009. Development of a new candidate H5N1 avian influenza virus for pre-pandemic vaccination production. Influenza and Other Respiratory Viruses. 3:287-295.
Interpretive Summary: H5N1 high pathogenicity (HP) avian influenza (AI) has caused infection in humans. This study developed a vaccine virus by using genes from an HPAI (high pathogenicity avian influenza) virus and the PR8 vaccine strain. Using a ferret model, the vaccine protected against a clade 2.3.4 H5N1 HPAI virus. In addition, the vaccine satisfied agricultural safety requirements for chickens. The vaccine candidate also proved attenuated and safe in ferrets, and therefore merits consideration to establish its safety and immunogenicity in humans as killed vaccine.
Technical 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 sector 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. Variant H5N1 viruses termed clade 2.3.4 emerged in 2005 and have 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 World Health Organization (WHO) pandemic vaccine development guidelines and containing 6 genes from A/Puerto Rico/8/34 as well as the NA (neuraminidase) and HA (hemagglutinin) genomic segments from the A/Anhui/01/2005 virus. The multibasic 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.