A booster of Delta-Omicron RBD-dimer protein subunit vaccine augments sera neutralization of Omicron sub-variants BA.1/BA.2/BA.2.12.1/BA.4/BA.5

ABSTRACT

The SARS-CoV-2 Omicron variants of concern (VOCs) showed severe resistance to the early-approved COVID-19 vaccines-induced immune responses. The breakthrough infections by the Omicron VOCs are currently the major challenge for pandemic control. Therefore, booster vaccination is crucial to enhance immune responses and protective efficacy. Previously, we developed a protein subunit COVID-19 vaccine ZF2001, based on the immunogen of receptor-binding domain (RBD) homodimer, which was approved in China and other countries. To adapt SARS-CoV-2 variants, we further developed chimeric Delta-Omicron BA.1 RBD-dimer immunogen which induced broad immune responses against SARS-CoV-2 variants. In this study, we tested the boosting effect of this chimeric RBD-dimer vaccine in mice after priming with two doses of inactivated vaccines, compared with a booster of inactivated vaccine or ZF2001. The results demonstrated that boosting with bivalent Delta-Omicron BA.1 vaccine greatly promoted the neutralizing activity of the sera to all tested SARS-CoV-2 variants. Therefore, the Delta-Omicron chimeric RBD-dimer vaccine is a feasible booster for those with prior vaccination of COVID-19 inactivated vaccines.

KEYWORDS:

• SARS-CoV-2
• Omicron
• ZF2001
• RBD-dimer
• vaccine

Acknowledgments

We would like to thank Beijing Institute of Biological Products and Anhui Zhifei Longcom Biopharmaceutical for providing vaccines for the animal experiment.

Disclosure statement

Y.A., T.Z., L.D., K.X., and G.F.G. are listed in the patent as the inventors of the prototype RBD-dimer as coronavirus vaccines. T.Z., L.D., K.X. and G.F.G are listed in the patent as the inventors of the pending patent applications for chimeric Delta-Omicron RBD-dimer as coronavirus vaccine. H.W. is an employee of Beijing Institute of Biological Products Company Limited. The other authors declare that they have no competing interests.

Additional information

Funding

This work was supported by National Key Research and Development Program of China: [Grant Number 2020YFA0907100]; National Natural Science Foundation of China: [Grant Number 82041048, 81991494 and 82202030]; Bill and Melinda Gates Foundation: [Grant Number INV-027420]; Chinese Academy of Sciences: [Grant Number YSBR-010]; Excellent Young Scientist Program from NSFC: [Grant Number 82122031]; Youth Innovation Promotion Association CAS: [Grant Number 2018113].