tetano
Editor, Senior Moderator
Emerg Microbes Infect
. 2023 Jul 3;2231573.
doi: 10.1080/22221751.2023.2231573. Online ahead of print. Rational design of an influenza-COVID-19 chimeric protective vaccine with S-RBD and HA-stalk
Yulei Li[SUP] 1 [/SUP], Peipei Liu[SUP] 2 [/SUP], Tianjiao Hao[SUP] 3 4 [/SUP], Sheng Liu[SUP] 5 [/SUP], Xi Wang[SUP] 3 4 [/SUP], Yufeng Xie[SUP] 6 [/SUP], Ke Xu[SUP] 2 [/SUP], Wenwen Lei[SUP] 2 [/SUP], Cheng Zhang[SUP] 7 [/SUP], Pu Han[SUP] 3 [/SUP], Ying Li[SUP] 1 [/SUP], Xiyue Jin[SUP] 8 [/SUP], Yu Huan[SUP] 3 4 [/SUP], Yafei Lu[SUP] 3 4 [/SUP], Rong Zhang[SUP] 9 [/SUP], Xiaoyan Li[SUP] 10 [/SUP], Xin Zhao[SUP] 3 [/SUP], Kun Xu[SUP] 11 [/SUP], Pu Liao[SUP] 12 [/SUP], Xuancheng Lu[SUP] 10 [/SUP], Yuhai Bi[SUP] 3 4 [/SUP], Hao Song[SUP] 4 11 [/SUP], Guizhen Wu[SUP] 2 [/SUP], Baoli Zhu[SUP] 3 4 13 [/SUP], George F Gao[SUP] 1 2 3 11 [/SUP]
Affiliations
Highly contagious respiratory illnesses like influenza and COVID-19 pose serious risks to public health. A two-in-one vaccine would be ideal to avoid multiple vaccinations for these diseases. Here, we generated a chimeric receptor binding domain of the spike protein (S-RBD) and hemagglutinin (HA)-stalk-based vaccine for both SARS-CoV-2 and influenza viruses. The S-RBD from SARS-CoV-2 Delta was fused to the headless HA from H1N1 (H1Delta), creating a chimera that forms trimers in solution. The cryo-electron microscopy structure of the chimeric protein complexed with the RBD-targeting CB6 and the HA-stalk-targeting CR9114 antibodies shows that the trimeric protein is stable and accessible for neutralizing antibody binding. Immunization with the vaccine elicited high and long-lasting neutralizing antibodies and effectively protected mice against the challenges of lethal H1N1 or heterosubtypic H5N8, as well as the SARS-CoV-2 Delta or Omicron BA.2 variants. Overall, this study offers a two-in-one universal vaccine design to combat infections caused by both SARS-CoV-2 variants of concern and influenza viruses.
Keywords: Omicron; SARS-CoV-2; Universal vaccine; broadly neutralizing antibody; chimeric antigen; influenza; subunit vaccine.
. 2023 Jul 3;2231573.
doi: 10.1080/22221751.2023.2231573. Online ahead of print. Rational design of an influenza-COVID-19 chimeric protective vaccine with S-RBD and HA-stalk
Yulei Li[SUP] 1 [/SUP], Peipei Liu[SUP] 2 [/SUP], Tianjiao Hao[SUP] 3 4 [/SUP], Sheng Liu[SUP] 5 [/SUP], Xi Wang[SUP] 3 4 [/SUP], Yufeng Xie[SUP] 6 [/SUP], Ke Xu[SUP] 2 [/SUP], Wenwen Lei[SUP] 2 [/SUP], Cheng Zhang[SUP] 7 [/SUP], Pu Han[SUP] 3 [/SUP], Ying Li[SUP] 1 [/SUP], Xiyue Jin[SUP] 8 [/SUP], Yu Huan[SUP] 3 4 [/SUP], Yafei Lu[SUP] 3 4 [/SUP], Rong Zhang[SUP] 9 [/SUP], Xiaoyan Li[SUP] 10 [/SUP], Xin Zhao[SUP] 3 [/SUP], Kun Xu[SUP] 11 [/SUP], Pu Liao[SUP] 12 [/SUP], Xuancheng Lu[SUP] 10 [/SUP], Yuhai Bi[SUP] 3 4 [/SUP], Hao Song[SUP] 4 11 [/SUP], Guizhen Wu[SUP] 2 [/SUP], Baoli Zhu[SUP] 3 4 13 [/SUP], George F Gao[SUP] 1 2 3 11 [/SUP]
Affiliations
- PMID: 37394992
- DOI: 10.1080/22221751.2023.2231573
Highly contagious respiratory illnesses like influenza and COVID-19 pose serious risks to public health. A two-in-one vaccine would be ideal to avoid multiple vaccinations for these diseases. Here, we generated a chimeric receptor binding domain of the spike protein (S-RBD) and hemagglutinin (HA)-stalk-based vaccine for both SARS-CoV-2 and influenza viruses. The S-RBD from SARS-CoV-2 Delta was fused to the headless HA from H1N1 (H1Delta), creating a chimera that forms trimers in solution. The cryo-electron microscopy structure of the chimeric protein complexed with the RBD-targeting CB6 and the HA-stalk-targeting CR9114 antibodies shows that the trimeric protein is stable and accessible for neutralizing antibody binding. Immunization with the vaccine elicited high and long-lasting neutralizing antibodies and effectively protected mice against the challenges of lethal H1N1 or heterosubtypic H5N8, as well as the SARS-CoV-2 Delta or Omicron BA.2 variants. Overall, this study offers a two-in-one universal vaccine design to combat infections caused by both SARS-CoV-2 variants of concern and influenza viruses.
Keywords: Omicron; SARS-CoV-2; Universal vaccine; broadly neutralizing antibody; chimeric antigen; influenza; subunit vaccine.