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Title: GENERATION AND EVALUATION OF AN INFLUENZA A/H9N2 HIGH-GROWTH REASSORTANT VIRUS AS A PANDEMIC VACCINE CANDIDATE

Author
item CHEN, HUALAN - CDC - ATLANTA, GA
item SUBBARAO, KANTA - CDC - ATLANTA, GA
item Swayne, David
item CHEN, QI - CDC - ATLANTA, GA
item LU, XIUHUA - CDC - ATLANTA, GA
item KATZ, JACQUELINE - CDC - ATLANTA, GA
item COX, NANCY - CDC - ATLANTA, GA
item MATSUOKA, YUMILO - CDC - ATLANTA, GA

Submitted to: Vaccine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/2/2002
Publication Date: 3/1/2003
Citation: Swayne, D.E., Chen, H., Subbarao, K., Chen, Q., Lu, X., Katz, J., Cox, N., Matsuoka, Y. Generation And Evaluation Of An Influenza A/H9N2 High-Growth Reassortant Virus As A Pandemic Vaccine Candidate. Vaccine-2003, 21:1974-1979.

Interpretive Summary: H9N2 subtype avian influenza viruses (AIV) are widely distributed in birds and were isolated from humans in Hong Kong and China in 1999. This raised concern for the potential of widespread human infections. We generated a new vaccine containing the hemagglutinin (HA) and neuraminidase (NA) genes from H9N2 AIV and 6 internal genes from a human influenza virus. This hybrid virus was not deadly for mice or chickens, but when used as an inactivated vaccine, protected mice from the original H9N2 AIV. These results indicate that the new hybrid virus has properties that are desirable in a vaccine seed virus and is suitable for evaluation in humans for use in the event of a pandemic influenza outbreak.

Technical Abstract: H9N2 subtype avian influenza viruses (AIV) are widely distributed in avian species and were isolated from humans in Hong Kong, SAR and Guangdong province, China in 1999, raising concern of the potential for pandemic spread. We generated a high growth reassortant virus (G9/PR8) that contains the hemagglutinin (HA) and neuraminidase (NA) genes from H9N2 avian influenza virus A/chicken/Hong Kong/G9/97(G9) and 6 internal genes from A/Puerto Rico/8/34 (PR8) by genetic reassortment for evaluation as a potential vaccine candidate in humans. Pathogenicity studies showed that the G9/PR8 reassortant was not highly pathogenic for mice or chickens. Two doses of a formalin-inactivated G9/PR8 virus vaccine induced hemagglutination inhibition (HI) antibodies and conferred complete protection against challenge with G9 and the antigenically distinct H9N2 A/Hong Kong/1073/99 (G1-like) viruses in a mouse model. These results indicate that the high growth G9/PR8 reassortant has properties that are desirable in a vaccine seed virus and is suitable for evaluation in humans for use in the event of a pandemic.