| Autor: |
Zhao, Yongliang, Ni, Wenjia, Liang, Simeng, Dong, Lianghui, Xiang, Min, Cai, Zeng, Niu, Danping, Zhang, Qiuhan, Wang, Dehe, Zheng, Yucheng, Zhang, Zhen, Zhou, Dan, Guo, Wenhua, Pan, Yongbing, Wu, Xiaoli, Yang, Yimin, Jing, Zhaofei, Jiang, Yongzhong, Chen, Yu, Yan, Huan |
| Předmět: |
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| Zdroj: |
Science Translational Medicine; 1/4/2023, Vol. 15 Issue 677, p1-14, 14p |
| Abstrakt: |
SARS-CoV-2 continues to accumulate mutations to evade immunity, leading to breakthrough infections after vaccination. How researchers can anticipate the evolutionary trajectory of the virus in advance in the design of next-generation vaccines requires investigation. Here, we performed a comprehensive study of 11,650,487 SARS-CoV-2 sequences, which revealed that the SARS-CoV-2 spike (S) protein evolved not randomly but into directional paths of either high infectivity plus low immune resistance or low infectivity plus high immune resistance. The viral infectivity and immune resistance of variants are generally incompatible, except for limited variants such as Beta and Kappa. The Omicron variant has the highest immune resistance but showed high infectivity in only one of the tested cell lines. To provide cross-clade immunity against variants that undergo diverse evolutionary pathways, we designed a new pan-vaccine antigen (Span). Span was designed by analyzing the homology of 2675 SARS-CoV-2 S protein sequences from the NCBI database before the Delta variant emerged. The refined Span protein harbors high-frequency residues at given positions that reflect cross-clade generality in sequence evolution. Compared with a prototype wild-type (Swt) vaccine, which, when administered to mice, induced serum with decreased neutralization activity against emerging variants, Span vaccination of mice elicited broad immunity to a wide range of variants, including those that emerged after our design. Moreover, vaccinating mice with a heterologous Span booster conferred complete protection against lethal infection with the Omicron variant. Our results highlight the importance and feasibility of a universal vaccine to fight against SARS-CoV-2 antigenic drift. Protection from a vaccine that Spans viral variants: Despite the success of the early generations of SARS-CoV-2 vaccines, viral evolution and immune evasion has made the development of next-generation broadly protective vaccines essential. Here, Zhao et al. used the evolutionary history of the SARS-CoV-2 S protein to develop Span, a vaccine antigen that carries amino acid residues that are consistent across SARS-CoV-2 strains. When administered to mice, Span elicited a more broadly neutralizing antibody response than a wild-type S protein vaccine. Span also conferred substantial protection against challenge with the Beta, Delta, and Omicron variants, despite Delta and Omicron arising after Span was designed. Together, these data support further development of Span as a vaccine antigen. —CM [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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