A mosaic-type trimeric RBD-based COVID-19 vaccine candidate induces potent neutralization against Omicron and other SARS-CoV-2 variants
Abstract
Large-scale populations in the world have been vaccinated with COVID-19 vaccines, however, breakthrough infections of SARS-CoV-2 are still growing rapidly due to the emergence of immune-evasive variants, especially Omicron. It is urgent to develop effective broad-spectrum vaccines to better control the pandemic of these variants. Here, we present a mosaic-type trimeric form of spike receptor-binding domain (mos-tri-RBD) as a broad-spectrum vaccine candidate, which carries the key mutations from Omicron and other circulating variants. Tests in rats showed that the designed mos-tri-RBD, whether used alone or as a booster shot, elicited potent cross-neutralizing antibodies against not only Omicron but also other immune-evasive variants. Neutralizing antibody ID50 titers induced by mos-tri-RBD were substantially higher than those elicited by homo-tri-RBD (containing homologous RBDs from prototype strain) or the BIBP inactivated COVID-19 vaccine (BBIBP-CorV). Our study indicates that mos-tri-RBD is highly immunogenic, which may serve as a broad-spectrum vaccine candidate in combating SARS-CoV-2 variants including Omicron.
Data availability
Figure 1 - Source Data 1, Figure 1 - Source Data 2, Figure 2 - Source Data 1, Figure 3 - Source Data 1 and Figure 4 - Source Data 1 contain the numerical data used to generate the figures. The gene sequence of the spike region of the Omicron BA.1.1 virus used in the live virus neutralization assay is provided in Appendix 1-figure 1, and the residue mutations in the Omicron BA.1.1 spike region compared to that of the prototype virus are provided in Appendix 1-figure 2.
Article and author information
Author details
Funding
National Vaccine and Serum Institute (KTZC1900026C)
- Jing Zhang
National Vaccine and Serum Institute (KTZC1900026C)
- Qi Ming Li
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Alex Sigal, University of KwaZulu-Natal, South Africa
Ethics
Animal experimentation: Animal experiments were approved by the Institutional Animal Care and Use Committee (IACUC) of the National Vaccine and Serum Institute (NVSI) (No. NVSI-RCD-JSDW-ER-2021238, NVSI-RCD-JSDW-ER-2022015) and conducted under the regulations for the administration of affairs concerning experimental animals of China (2017).
Version history
- Received: March 14, 2022
- Preprint posted: March 29, 2022 (view preprint)
- Accepted: August 22, 2022
- Accepted Manuscript published: August 25, 2022 (version 1)
- Version of Record published: September 16, 2022 (version 2)
Copyright
© 2022, Zhang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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