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

被引:13
作者
Choi, Eun-hye [1 ,2 ]
Song, Min-Suk [1 ,2 ]
Park, Su-Jin [1 ,2 ]
Pascua, Philippe Noriel Q. [1 ,2 ]
Baek, Yun Hee [1 ,2 ]
Kwon, Hyeok-il [1 ,2 ]
Kim, Eun-Ha [1 ,2 ]
Kim, Semi [1 ,2 ]
Jang, Hyung-Kwan [3 ,4 ,5 ]
Poo, Haryoung [6 ]
Kim, Chul-Joong [7 ]
Choi, Young Ki [1 ,2 ]
机构
[1] Chungbuk Natl Univ, Dept Microbiol, Coll Med, Cheongju 361763, South Korea
[2] Chungbuk Natl Univ, Med Res Inst, Cheongju 361763, South Korea
[3] Chonbuk Natl Univ, Coll Vet Med, Dept Infect Dis, Jeonju, South Korea
[4] Chonbuk Natl Univ, Coll Vet Med, Dept Avian Dis, Jeonju, South Korea
[5] Chonbuk Natl Univ, Korea Zoonosis Res Inst, Jeonju, South Korea
[6] Korean Res Inst Biosci & Biotechnol, Taejon, South Korea
[7] Chungnam Natl Univ, Coll Vet Med, Taejon 305764, South Korea
关键词
TOXIC LYMPHOCYTES-T; A VIRUS; CROSS-PROTECTION; TRUNCATED NS1; RIG-I; INFECTION; PROTEIN; HEMAGGLUTININ; MICE; EVOLUTION;
D O I
10.1007/s00705-015-2442-y
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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-beta activation than viruses with full-length NS1 proteins and were correspondingly attenuated in mice. Intranasal vaccination with a single dose (10(4.0) 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.
引用
收藏
页码:1729 / 1740
页数:12
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