tetano
Editor, Senior Moderator
Viruses
. 2021 Dec 3;13(12):2420.
doi: 10.3390/v13122420.
Safety, Immunogenicity, and Protective Efficacy of an H5N1 Chimeric Cold-Adapted Attenuated Virus Vaccine in a Mouse Model
Weiyang Sun[SUP] 1 [/SUP], Zhenfei Wang[SUP] 1 2 [/SUP], Yue Sun[SUP] 1 3 [/SUP], Dongxu Li[SUP] 1 4 [/SUP], Menghan Zhu[SUP] 1 5 [/SUP], Menglin Zhao[SUP] 1 [/SUP], Yutian Wang[SUP] 1 [/SUP], Jiaqi Xu[SUP] 1 6 [/SUP], Yunyi Kong[SUP] 1 [/SUP], Yuanguo Li[SUP] 1 [/SUP], Na Feng[SUP] 1 [/SUP], Tiecheng Wang[SUP] 1 [/SUP], Yongkun Zhao[SUP] 1 [/SUP], Songtao Yang[SUP] 1 [/SUP], Yuwei Gao[SUP] 1 7 [/SUP], Xianzhu Xia[SUP] 1 7 [/SUP]
Affiliations
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.
Keywords: H5N1 influenza virus; chimeric vaccine; immune protection; mice.
. 2021 Dec 3;13(12):2420.
doi: 10.3390/v13122420.
Safety, Immunogenicity, and Protective Efficacy of an H5N1 Chimeric Cold-Adapted Attenuated Virus Vaccine in a Mouse Model
Weiyang Sun[SUP] 1 [/SUP], Zhenfei Wang[SUP] 1 2 [/SUP], Yue Sun[SUP] 1 3 [/SUP], Dongxu Li[SUP] 1 4 [/SUP], Menghan Zhu[SUP] 1 5 [/SUP], Menglin Zhao[SUP] 1 [/SUP], Yutian Wang[SUP] 1 [/SUP], Jiaqi Xu[SUP] 1 6 [/SUP], Yunyi Kong[SUP] 1 [/SUP], Yuanguo Li[SUP] 1 [/SUP], Na Feng[SUP] 1 [/SUP], Tiecheng Wang[SUP] 1 [/SUP], Yongkun Zhao[SUP] 1 [/SUP], Songtao Yang[SUP] 1 [/SUP], Yuwei Gao[SUP] 1 7 [/SUP], Xianzhu Xia[SUP] 1 7 [/SUP]
Affiliations
- PMID: 34960689
- DOI: 10.3390/v13122420
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.
Keywords: H5N1 influenza virus; chimeric vaccine; immune protection; mice.