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Journal of Virology, January 2009, p. 65-72, Vol. 83, No. 1
0022-538X/09/$08.00+0     doi:10.1128/JVI.01775-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Evaluation of Live Attenuated Influenza A Virus H6 Vaccines in Mice and Ferrets{triangledown}

Zhongying Chen,1,{dagger} Celia Santos,2,{dagger} Amy Aspelund,1 Laura Gillim-Ross,2,{ddagger} Hong Jin,1 George Kemble,1 and Kanta Subbarao2*

MedImmune, Mountain View, California 94043,1 Laboratory of Infectious Diseases, NIAID, NIH, Bethesda, Maryland 208922

Received 22 August 2008/ Accepted 13 October 2008

Avian influenza A virus A/teal/HK/W312/97 (H6N1) possesses seven gene segments that are highly homologous to those of highly pathogenic human influenza H5N1 viruses, suggesting that a W312-like H6N1 virus might have been involved in the generation of the A/HK/97 H5N1 viruses. The continuous circulation and reassortment of influenza H6 subtype viruses in birds highlight the need to develop an H6 vaccine to prevent potential influenza pandemics caused by the H6 viruses. Based on the serum antibody cross-reactivity data obtained from 14 different H6 viruses from Eurasian and North American lineages, A/duck/HK/182/77, A/teal/HK/W312/97, and A/mallard/Alberta/89/85 were selected to produce live attenuated H6 candidate vaccines. Each of the H6 vaccine strains is a 6:2 reassortant ca virus containing HA and NA gene segments from an H6 virus and the six internal gene segments from cold-adapted A/Ann Arbor/6/60 (AA ca), the master donor virus that is used to make live attenuated influenza virus FluMist (intranasal) vaccine. All three H6 vaccine candidates exhibited phenotypic properties of temperature sensitivity (ts), ca, and attenuation (att) conferred by the internal gene segments from AA ca. Intranasal administration of a single dose of the three H6 ca vaccine viruses induced neutralizing antibodies in mice and ferrets and fully protected mice and ferrets from homologous wild-type (wt) virus challenge. Among the three H6 vaccine candidates, the A/teal/HK/W312/97 ca virus provided the broadest cross-protection against challenge with three antigenically distinct H6 wt viruses. These data support the rationale for further evaluating the A/teal/HK/W312/97 ca vaccine in humans.

* Corresponding author. Mailing address: Laboratory of Infectious Diseases, NIAID, NIH, Bldg. 33/Room 3E13C.1, 33 North Dr., MSC 3203, Bethesda, MD 20892. Phone: (301) 451-3839. Fax: (301) 480-4749. E-mail: ksubbarao{at}niaid.nih.gov

{triangledown} Published ahead of print on 22 October 2008.

{dagger} Both authors contributed to the work equally.

{ddagger} Present address: Colorado Department of Public Health and Environment, 8100 Lowry Blvd., Denver, CO 80230.

Journal of Virology, January 2009, p. 65-72, Vol. 83, No. 1
0022-538X/09/$08.00+0     doi:10.1128/JVI.01775-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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