Rational design of an influenza-COVID-19 chimeric protective vaccine with HA-stalk and S-RBD

• Published in: Emerging microbes & infections 2023-12, Vol.12 (2), p.2231573-2231573
• Main Authors: Li, Yulei, Liu, Peipei, Hao, Tianjiao, Liu, Sheng, Wang, Xi, Xie, Yufeng, Xu, Ke, Lei, Wenwen, Zhang, Cheng, Han, Pu, Li, Ying, Jin, Xiyue, Huan, Yu, Lu, Yafei, Zhang, Rong, Li, Xiaoyan, Zhao, Xin, Xu, Kun, Liao, Pu, Lu, Xuancheng, Bi, Yuhai, Song, Hao, Wu, Guizhen, Zhu, Baoli, Gao, George F.
• Format: Article
• Language: English
• Subjects: broadly neutralizing antibody; chimeric antigen; Coronaviruses; COVID-19 vaccines; Immunization; Influenza; Omicron; Proteins; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; subunit vaccine; Universal vaccine
• ISSN: 2222-1751; 2222-1751
• 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.