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Title: A live attenuated cold adapted influenza A H7N3 virus vaccine provides protection against homologous and heterologous H7 viruses in mice and ferrets

Author
item JOSEPH, TOMY - NIAID, NIH, BETHESDA, MD
item MCAULIFFE, JOSEPHINE - NIAID, NIH, BETHESDA, MD
item LU, BIN - MEDIMMUNE INC, CALIF
item VOGEL, LEATRICE - NIAID, NIH, BETHESDA, MD
item Swayne, David
item JIN, HONG - MEDIMMUNE INC, CALIF
item KEMBLE, GEORGE - MEDIMMUNE INC, CALIF
item SUBBARAO, KANTA - NIAID, NIH, BETHESDA, MD

Submitted to: Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/19/2008
Publication Date: 8/15/2008
Citation: Joseph, T., Mcauliffe, J., Lu, B., Vogel, L., Swayne, D.E., Jin, H., Kemble, G., Subbarao, K. 2008. A live attenuated cold adapted influenza A H7N3 virus vaccine provides protection against homologous and heterologous H7 viruses in mice and ferrets. Virology. 378(1):123-132.

Interpretive Summary: Various avian influenza viruses have an unknown potential to become human pandemic influenza viruses. This study developed an H7N3 live weakened virus vaccine by using advanced biotechnology. This vaccine did not infect chickens, did not cause disease in mice and ferrets which are animal models for humans, and only grew at the lower temperatures in the nasal cavity. Administering the vaccine in the nose protected mice and ferrets against challenge by H7 influenza viruses which support further evaluation of the vaccine in clinical trials.

Technical Abstract: The appearance of human infections caused by avian influenza A H7 subtype viruses underscore their pandemic potential and the need to develop vaccines to protect humans from viruses of this subtype. A live attenuated H7N3 virus vaccine was generated by reverse genetics using the HA and NA genes of a low pathogenicity A/chicken/BC/CN-6/04 (H7N3) virus and the six internal protein genes of the cold-adapted A/Ann Arbor/6/60 ca (H2N2) virus. The reassortant H7N3 BC 04 ca vaccine virus was temperature sensitive and showed attenuation in mice and ferrets. Intranasal immunization with one dose of the vaccine protected mice and ferrets when challenged with homologous and heterologous H7 viruses. This study also suggests that mice are an acceptable alternative to ferrets as a model for preclinical evaluation of H7 virus vaccines. The safety, immunogenicity, and efficacy of this vaccine in mice and ferrets support the evaluation of this vaccine in clinical trials.