Design of a mutation-integrated trimeric RBD with broad protection against SARS-CoV-2.
Cell Discov
; 8(1): 17, 2022 Feb 15.
Article
in English
| MEDLINE | ID: covidwho-1692628
ABSTRACT
The continuous emergence of SARS-CoV-2 variants highlights the need of developing vaccines with broad protection. Here, according to the immune-escape capability and evolutionary convergence, the representative SARS-CoV-2 strains carrying the hotspot mutations were selected. Then, guided by structural and computational analyses, we present a mutation-integrated trimeric form of spike receptor-binding domain (mutI-tri-RBD) as a broadly protective vaccine candidate, which combined heterologous RBDs from different representative strains into a hybrid immunogen and integrated immune-escape hotspots into a single antigen. When compared with a homo-tri-RBD vaccine candidate in the stage of phase II trial, of which all three RBDs are derived from the SARS-CoV-2 prototype strain, mutI-tri-RBD induced significantly higher neutralizing antibody titers against the Delta and Beta variants, and maintained a similar immune response against the prototype strain. Pseudo-virus neutralization assay demonstrated that mutI-tri-RBD also induced broadly strong neutralizing activities against all tested 23 SARS-CoV-2 variants. The in vivo protective capability of mutI-tri-RBD was further validated in hACE2-transgenic mice challenged by the live virus, and the results showed that mutI-tri-RBD provided potent protection not only against the SARS-CoV-2 prototype strain but also against the Delta and Beta variants.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Type of study:
Prognostic study
/
Randomized controlled trials
Topics:
Vaccines
/
Variants
Language:
English
Journal:
Cell Discov
Year:
2022
Document Type:
Article
Affiliation country:
S41421-022-00383-5
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