| Autor: |
Rui Shi, Jiawei Zeng, Ling Xu, Fengze Wang, Xiaomin Duan, Yue Wang, Zheng Wu, Dandan Yu, Qingrui Huang, Yong-Gang Yao, Jinghua Yan |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
EBioMedicine, Vol 85, Iss , Pp 104297- (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2352-3964 |
| DOI: |
10.1016/j.ebiom.2022.104297 |
| Popis: |
Summary: Background: Increasing severe morbidity and mortality by simultaneous or sequential infections with SARS-CoV-2 and influenza A viruses (IAV), especially in the elderly and obese patients, highlight the urgency of developing a combination vaccine against COVID-19 and influenza. Methods: Self-assembling SARS-CoV-2 RBD-trimer and Influenza H1N1 HA1-trimer antigens were constructed, upon the stable fusion core in post-fusion conformation. Immunogenicity of SARS-CoV-2 RBD-trimer vaccine and H1N1 HA1-trimer antigens candidates were evaluated in mice. Protection efficacy of a combination vaccine candidate against SARS-CoV-2 and IAV challenge was identified using the K18-hACE2 mouse model. Findings: Both the resultant RBD-trimer for SARS-CoV-2 and HA1-trimer for H1N1 influenza fully exposed receptor-binding motifs (RBM) or receptor-binding site (RBS). Two-dose RBD-trimer induced significantly higher binding and neutralizing antibody titers, and also a strong Th1/Th2 balanced cellular immune response in mice. Similarly, the HA1-trimer vaccine was confirmed to exhibit potent immunogenicity in mice. A combination vaccine candidate, composed of RBD-trimer and HA1-trimer, afforded high protection efficacy in mouse models against stringent lethal SARS-CoV-2 and homogenous H1N1 influenza co-infection, characterized by 100% survival rate. Interpretation: Our results represent a proof of concept for a combined vaccine candidate based on trimerized receptor binding domain against co-epidemics of COVID-19 and influenza. Funding: This project was funded by the Strategic Priority Research Program of CAS (XDB29040201), the National Natural Science Foundation of China (81830050, 81901680, and 32070569) and China Postdoctoral Science Foundation (2021M703450). |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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