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Archives of Virology
Published in: Archives of Virology 7/2015

01-07-2015 | Original Article

Development of a dual-protective live attenuated vaccine against H5N1 and H9N2 avian influenza viruses by modifying the NS1 gene

Authors: Eun-hye Choi, Min-Suk Song, Su-Jin Park, Philippe Noriel Q. Pascua, Yun Hee Baek, Hyeok-il Kwon, Eun-Ha Kim, Semi Kim, Hyung-Kwan Jang, Haryoung Poo, Chul-Joong Kim, Young Ki Choi

Published in: Archives of Virology | Issue 7/2015

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Abstract

An increasing number of outbreaks of avian influenza H5N1 and H9N2 viruses in poultry have caused serious economic losses and raised concerns for human health due to the risk of zoonotic transmission. However, licensed H5N1 and H9N2 vaccines for animals and humans have not been developed. Thus, to develop a dual H5N1 and H9N2 live-attenuated influenza vaccine (LAIV), the HA and NA genes from a virulent mouse-adapted avian H5N2 (A/WB/Korea/ma81/06) virus and a recently isolated chicken H9N2 (A/CK/Korea/116/06) virus, respectively, were introduced into the A/Puerto Rico/8/34 backbone expressing truncated NS1 proteins (NS1-73, NS1-86, NS1-101, NS1-122) but still possessing a full-length NS gene. Two H5N2/NS1-LAIV viruses (H5N2/NS1-86 and H5N2/NS1-101) were highly attenuated compared with the full-length and remaining H5N2/NS-LAIV viruses in a mouse model. Furthermore, viruses containing NS1 modifications were found to induce more IFN-β activation than viruses with full-length NS1 proteins and were correspondingly attenuated in mice. Intranasal vaccination with a single dose (104.0 PFU/ml) of these viruses completely protected mice from a lethal challenge with the homologous A/WB/Korea/ma81/06 (H5N2), heterologous highly pathogenic A/EM/Korea/W149/06 (H5N1), and heterosubtypic highly virulent mouse-adapted H9N2 viruses. This study clearly demonstrates that the modified H5N2/NS1-LAIV viruses attenuated through the introduction of mutations in the NS1 coding region display characteristics that are desirable for live attenuated vaccines and hold potential as vaccine candidates for mammalian hosts.
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Metadata
Title
Development of a dual-protective live attenuated vaccine against H5N1 and H9N2 avian influenza viruses by modifying the NS1 gene
Authors
Eun-hye Choi
Min-Suk Song
Su-Jin Park
Philippe Noriel Q. Pascua
Yun Hee Baek
Hyeok-il Kwon
Eun-Ha Kim
Semi Kim
Hyung-Kwan Jang
Haryoung Poo
Chul-Joong Kim
Young Ki Choi
Publication date
01-07-2015
Publisher
Springer Vienna
Published in
Archives of Virology / Issue 7/2015
Print ISSN: 0304-8608
Electronic ISSN: 1432-8798
DOI
https://doi.org/10.1007/s00705-015-2442-y

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