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Title: Development of a cross protective high growth reasssortant H7N7/PR8 virus for clinical evaluation as an inactivated pre-pandemic influenza vaccine

Author
item JADHAO, SAMADHAN - CDC, INFLUENZA BRANCH
item ACHENBACH, JENNA - CDC, INFLUENZA BRANCH
item Swayne, David
item DONIS, RUBEN - CDC, INFLUENZA BRANCH
item COX, NANCY - CDC, INFLUENZA BRANCH
item MATSUOKA, YUMIKO - CDC, INFLUENZA BRANCH

Submitted to: Vaccine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/14/2008
Publication Date: 2/13/2008
Citation: Jadhao, S.J., Achenbach, J., Swayne, D.E., Donis, R., Cox, N., Matsuoka, Y. 2008. Development of Eurasian H7N7/PR8 high growth reassortant virus for clinical evaluation as an inactivated pandemic influenza vaccine. Vaccine. 26:1742-1750.

Interpretive Summary: H7N7 high pathogenicity (HP) avian influenza (AI) was transmitted to humans in The Netherlands in 2003 causing eye infections and one fatality while the Canadian H7N3 low pathogenicity (LP) AI virus caused a mild human infection. This study developed a vaccine virus by using genes from two different LPAI viruses and the PR8 vaccine strain. Using a mouse vaccine model, the vaccine protected mice against both the Canadian H7N3 LPAI and Eurasian H7N7 HPAI viruses. In addition, the vaccine satisfied agricultural safety requirements for chickens. The vaccine candidate also proved attenuated and safe in mice, and therefore merits consideration to establish its safety and immunogenicity in humans.

Technical Abstract: Interspecies transmission of high pathogenicity (HP) H7N7 subtype avian influenza viruses in the Netherlands in 2003 caused zoonotic infections in 89 people, including one fatal case of acute respiratory distress syndrome. Public health preparedness approaches against emerging HP H7N7 influenza virus lineage with pandemic potential include the development of candidate subtype specific vaccines using low pathogenicity (LP) viruses as donors of hemagglutinin (HA) and neuraminidase (NA) genes that are antigenically closely related to avian influenza virus strains possessing pandemic potential. Based on these criteria, we identified two LP strains, A/mallard/Netherlands/12/2000 (H7N3) and A/mallard/Netherlands/2/2000 (H10N7), as donors of H7 HA and N7 NA genes. Adhering to current vaccine licensure regulations, we generated an antigenically broadly cross-reactive Eurasian H7N7/PR8 reassortant containing the desired surface glycoprotein genes from the mallard viruses on the backbone of high growth property conferring A/Puerto Rico/8/34 virus internal genes. Mice immunized with the formalin inactivated (FI) H7N7/PR8 whole virus vaccine with or without aluminum hydroxide (alum) adjuvant survived a lethal challenge with the Eurasian HP A/Netherlands/219/03 (NL219) human isolate. The vaccine also cross-protected mice at the pulmonary level against the North American A/Canada/444/04 (H7N3) LP human isolate. Despite poor immunogenicity of wild type FI NL219 vaccine it proved superior to reassortant FI H7N7/PR8 vaccine in restricting pulmonary replication of HP NL219 challenge virus. However, use of HP NL219 virus to produce human vaccine raises safety and regulatory concerns. Nevertheless, the reassortant H7N7/PR8 vaccine candidate conferred protection against the Eurasian and North American virus challenge and satisfied agricultural safety requirements for chickens. The vaccine candidate also proved attenuated and safe in mice, and therefore merits consideration to establish its safety and immunogenicity in humans.