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- Title
Safety, Immunogenicity, and Protective Efficacy of an H5N1 Chimeric Cold-Adapted Attenuated Virus Vaccine in a Mouse Model.
- Authors
Sun, Weiyang; Wang, Zhenfei; Sun, Yue; Li, Dongxu; Zhu, Menghan; Zhao, Menglin; Wang, Yutian; Xu, Jiaqi; Kong, Yunyi; Li, Yuanguo; Feng, Na; Wang, Tiecheng; Zhao, Yongkun; Yang, Songtao; Gao, Yuwei; Xia, Xianzhu
- Abstract
H5N1 influenza virus is a threat to public health worldwide. The virus can cause severe morbidity and mortality in humans. We constructed an H5N1 influenza candidate virus vaccine from the A/chicken/Guizhou/1153/2016 strain that was recommended by the World Health Organization. In this study, we designed an H5N1 chimeric influenza A/B vaccine based on a cold-adapted (ca) influenza B virus B/Vienna/1/99 backbone. We modified the ectodomain of H5N1 hemagglutinin (HA) protein, while retaining the packaging signals of influenza B virus, and then rescued a chimeric cold-adapted H5N1 candidate influenza vaccine through a reverse genetic system. The chimeric H5N1 vaccine replicated well in eggs and the Madin-Darby Canine Kidney cells. It maintained a temperature-sensitive and cold-adapted phenotype. The H5N1 vaccine was attenuated in mice. Hemagglutination inhibition (HAI) antibodies, micro-neutralizing (MN) antibodies, and IgG antibodies were induced in immunized mice, and the mucosal IgA antibody responses were detected in their lung lavage fluids. The IFN-γ-secretion and IL-4-secretion by the mouse splenocytes were induced after stimulation with the specific H5N1 HA protein. The chimeric H5N1 candidate vaccine protected mice against lethal challenge with a wild-type highly pathogenic avian H5N1 influenza virus. The chimeric H5 candidate vaccine is thus a potentially safe, attenuated, and reassortment-incompetent vaccine with circulating A viruses.
- Subjects
WORLD Health Organization; IMMUNOGLOBULINS; INFLUENZA; H5N1 Influenza; INFLUENZA B virus; VIRAL vaccines; AVIAN influenza A virus; IMMUNE response
- Publication
Viruses (1999-4915), 2021, Vol 13, Issue 12, p2420
- ISSN
1999-4915
- Publication type
Article
- DOI
10.3390/v13122420