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Title: Development of clade-specific and broadly reactive live attenuated influenza virus vaccines against rapidly evolving H5 subtype viruses
Authors: Kobporn Boonnak
Yumiko Matsuoka
Weijia Wang
Amorsolo L. Suguitan
Zhongying Chen
Myeisha Paskel
Mariana Baz
Ian Moore
Hong Jin
Kanta Subbarao
National Institute of Allergy and Infectious Diseases
MedImmune, Inc.
Mahidol University
Université Laval
World Health Organization, Australia
Keywords: Agricultural and Biological Sciences;Immunology and Microbiology
Issue Date: 1-Aug-2017
Citation: Journal of Virology. Vol.91, No.15 (2017)
Abstract: © 2017 American Society for Microbiology. We have developed pandemic live attenuated influenza vaccines (pLAIVs) against clade 1 H5N1 viruses on an Ann Arbor cold-adapted (ca) backbone that induced long-term immune memory. In 2015, many human infections caused by a new clade (clade of goose/Guangdong (gs/GD) lineage H5N1 viruses were reported in Egypt, which prompted updating of the H5N1 pLAIV. We explored two strategies to generate suitable pLAIVs. The first approach was to modify the hemagglutinin gene of a highly pathogenic wild-type (wt) clade virus, A/Egypt/N03434/2009 (Egy/09) (H5N1), with its unmodified neuraminidase (NA) gene; this virus was designated Egy/09 ca. The second approach was to select a low-pathogenicity avian influenza H5 virus that elicited antibodies that cross-reacted with a broad range of H5 viruses, including the Egypt H5N1 viruses, and contained a novel NA subtype for humans. We selected the lowpathogenicity A/duck/Hokkaido/69/2000 (H5N3) (dk/Hok/00) virus for this purpose. Both candidate vaccines were attenuated and immunogenic in ferrets, inducing antibodies that neutralized homologous and heterologous H5 viruses with different degrees of cross-reactivity; Egy/09 ca vaccine antisera were more specific for the gs/GD lineage viruses but did not neutralize recent North American isolates (clade, whereas antisera from dk/Hok/69 ca-vaccinated ferrets crossreacted with clade and 2.2.1 viruses but not clade 1 or 2.1 viruses. When vaccinated ferrets were challenged with homologous and heterologous H5 viruses, challenge virus replication was reduced in the respiratory tract. Thus, the two H5 pLAIV candidates are suitable for clinical development to protect humans from infection with different clades of H5 viruses.
ISSN: 10985514
Appears in Collections:Scopus 2016-2017

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