Open AccessEvaluation of Live Attenuated Influenza A Virus H6 Vaccines in Mice and Ferrets
Author(s) -
Zhongying Chen,
Celia Santos,
Amy Aspelund,
Laura Gillim-Ross,
Hong Jin,
George Kemble,
Kanta Subbarao
Publication year - 2009
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.01775-08
Subject(s) - virology , biology , virus , influenza a virus subtype h5n1 , reassortment , attenuated vaccine , nasal administration , influenza a virus , antibody , live attenuated influenza vaccine , h5n1 genetic structure , influenza vaccine , inactivated vaccine , gene , microbiology and biotechnology , immunology , virulence , genetics , covid-19 , medicine , infectious disease (medical specialty) , disease , pathology
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 reassortantca 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 (AAca ), 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 AAca . Intranasal administration of a single dose of the three H6ca 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/W312/97ca 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/W312/97ca vaccine in humans.