A recombinant receptor-binding domain in trimeric form generates completely protective immunity against SARS-CoV-2 infection in nonhuman primates

Yang, L.; Tian, D.; Han, J.-b.; Fan, W.; Zhang, Y.; Li, Y.; Sun, W.; Wei, Y.; Tian, X.; Yu, D.-d.; Feng, X.-l.; Cheng, G.; Zheng, Y.-t.; Bi, Y.; Liu, W.

doi:10.1101/2021.03.30.437647

bioRxiv · 10.1101/2021.03.30.437647

A recombinant receptor-binding domain in trimeric form generates completely protective immunity against SARS-CoV-2 infection in nonhuman primates

Yang, L.·Tian, D.·Han, J.-b.·Fan, W.·Zhang, Y.·Li, Y.·Sun, W.·Wei, Y.·Tian, X.·Yu, D.-d.·Feng, X.-l.·Cheng, G.·Zheng, Y.-t.·Bi, Y.·Liu, W.

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Abstract

Safe and effective vaccination is critical to combatting the COVID-19 pandemic. Here, we developed a trimeric SARS-CoV-2 receptor-binding domain (RBD) subunit vaccine candidate that simulates the natural structure of the spike (S) trimer glycoprotein. Immunization with RBD-trimer induced robust humoral and cellular immune responses and a high level of neutralizing antibodies that were maintained for at least 4 months. Moreover, the antibodies that were produced in response to the vaccine effectively neutralized the SARS-CoV-2 501Y.V2 variant. Of note, when the titers of the antibodies dropped to a sufficiently low level, only one boost quickly activated the anamnestic immune response, resulting in complete protection against the SARS-CoV-2 challenge in rhesus macaques without typical histopathological changes or viral replication in the lungs and other respiratory tissues. Our results indicated that immunization with SARS-CoV-2 RBD-trimer could raise long-term and broad immunity protection in nonhuman primates, thereby offering an optimal vaccination strategy against COVID-19.

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Yang, L., Tian, D., Han, J.-b., Fan, W., Zhang, Y., Li, Y., Sun, W., Wei, Y., Tian, X., Yu, D.-d., Feng, X.-l., Cheng, G., Zheng, Y.-t., Bi, Y., Liu, W.. 2021-03-30. A recombinant receptor-binding domain in trimeric form generates completely protective immunity against SARS-CoV-2 infection in nonhuman primates. https://doi.org/10.1101/2021.03.30.437647

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