Rapid development of SARS-CoV-2 receptor binding domain-conjugated nanoparticle vaccine candidate

Kang, Y.-F.; Sun, C.; Zhuang, Z.; Yuan, R.-Y.; Zheng, Q.-B.; Zhou, P.-P.; Li, J.-P.; Chen, X.-C.; Zhang, X.; Yu, X.-H.; Kong, X.-W.; Zhu, Q.-Y.; Xu, M.; Zhong, N.-S.; Zeng, Y.-X.; Feng, G.-K.; Ke, C.-W.; Zhao, J.-C.; Zeng, M.-S.

doi:10.1101/2020.11.03.366138

bioRxiv · 10.1101/2020.11.03.366138

Rapid development of SARS-CoV-2 receptor binding domain-conjugated nanoparticle vaccine candidate

Kang, Y.-F.·Sun, C.·Zhuang, Z.·Yuan, R.-Y.·Zheng, Q.-B.·Zhou, P.-P.·Li, J.-P.·Chen, X.-C.·Zhang, X.·Yu, X.-H.·Kong, X.-W.·Zhu, Q.-Y.·Xu, M.·Zhong, N.-S.·Zeng, Y.-X.·Feng, G.-K.·Ke, C.-W.·Zhao, J.-C.·Zeng, M.-S.

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Abstract

The ongoing of coronavirus disease 2019 (COVID-19) pandemic caused by novel SARS-CoV-2 coronavirus, resulting in economic losses and seriously threating the human health in worldwide, highlighting the urgent need of a stabilized, easily produced and effective preventive vaccine. The SARS-COV-2 spike protein receptor binding region (RBD) plays an important role in the process of viral binding receptor angiotensin-converting enzyme 2 (ACE2) and membrane fusion, making it an ideal target for vaccine development. In this study, we designed three different RBD-conjugated nanoparticles vaccine candidates, RBD-Ferritin (24-mer), RBD-mi3 (60-mer) and RBD-I53-50 (120-mer), with the application of covalent bond linking by SpyTag-SpyCatcher system. It was demonstrated that the neutralizing capability of sera from mice immunized with three RBD-conjugated nanoparticles adjuvanted with AddaVax or Sigma Systerm Adjuvant (SAS) after each immunization was ~8-to 120-fold greater than monomeric RBD group in SARS-CoV-2 pseudovirus and authentic virus neutralization assay. Most importantly, sera from RBD-conjugated NPs groups more efficiently blocked the binding of RBD to ACE2 or neutralizing antibody in vitro, a further proof of promising immunization effect. Besides, high physical stability and flexibility in assembly consolidated the benefit for rapid scale-up production of vaccine. These results supported that our designed SARS-CoV-2 RBD-conjugated nanoparticle was competitive vaccine candidate and the carrier nanoparticles could be adopted as universal platform for future vaccine development.

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Kang, Y.-F., Sun, C., Zhuang, Z., Yuan, R.-Y., Zheng, Q.-B., Zhou, P.-P., Li, J.-P., Chen, X.-C., Zhang, X., Yu, X.-H., Kong, X.-W., Zhu, Q.-Y., Xu, M., Zhong, N.-S., Zeng, Y.-X., Feng, G.-K., Ke, C.-W., Zhao, J.-C., Zeng, M.-S.. 2020-11-03. Rapid development of SARS-CoV-2 receptor binding domain-conjugated nanoparticle vaccine candidate. https://doi.org/10.1101/2020.11.03.366138

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