Immunization with the receptor-binding domain of SARS-CoV-2 elicits antibodies cross-neutralizing SARS-CoV-2 and SARS-CoV without antibody-dependent enhancement

Zang, J.; Gu, C.; Zhou, B.; Zhang, C.; Yang, Y.; Xu, S.; Zhang, X.; Zhou, Y.; Bai, L.; Wu, Y.; Sun, Z.; Zhang, R.; Deng, Q.; Yuan, Z.; Tang, H.; Qu, D.; Lavillette, D.; Xie, Y.; Huang, Z.

doi:10.1101/2020.05.21.107565

bioRxiv · 10.1101/2020.05.21.107565

Immunization with the receptor-binding domain of SARS-CoV-2 elicits antibodies cross-neutralizing SARS-CoV-2 and SARS-CoV without antibody-dependent enhancement

Zang, J.·Gu, C.·Zhou, B.·Zhang, C.·Yang, Y.·Xu, S.·Zhang, X.·Zhou, Y.·Bai, L.·Wu, Y.·Sun, Z.·Zhang, R.·Deng, Q.·Yuan, Z.·Tang, H.·Qu, D.·Lavillette, D.·Xie, Y.·Huang, Z.

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Abstract

Recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the ongoing coronavirus disease 2019 (COVID-19) pandemic. Currently, there is no vaccine available for preventing SARS-CoV-2 infection. Like closely related severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-2 also uses its receptor-binding domain (RBD) on the spike (S) protein to engage the host receptor, human angiotensin-converting enzyme 2 (ACE2), facilitating subsequent viral entry. Here we report the immunogenicity and vaccine potential of SARS-CoV-2 RBD (SARS2-RBD)-based recombinant proteins. Immunization with SARS2-RBD recombinant proteins potently induced a multi-functional antibody response in mice. The resulting antisera could efficiently block the interaction between SARS2-RBD and ACE2, inhibit S-mediated cell-cell fusion, and neutralize both SARS-CoV-2 pseudovirus entry and authentic SARS-CoV-2 infection. In addition, the anti-RBD sera also exhibited cross binding, ACE2-blockade, and neutralization effects towards SARS-CoV. More importantly, we found that the anti-RBD sera did not promote antibody-dependent enhancement of either SARS-CoV-2 pseudovirus entry or authentic virus infection of Fc receptor-bearing cells. These findings provide a solid foundation for developing RBD-based subunit vaccines for SARS-CoV2.

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Zang, J., Gu, C., Zhou, B., Zhang, C., Yang, Y., Xu, S., Zhang, X., Zhou, Y., Bai, L., Wu, Y., Sun, Z., Zhang, R., Deng, Q., Yuan, Z., Tang, H., Qu, D., Lavillette, D., Xie, Y., Huang, Z.. 2020-05-21. Immunization with the receptor-binding domain of SARS-CoV-2 elicits antibodies cross-neutralizing SARS-CoV-2 and SARS-CoV without antibody-dependent enhancement. https://doi.org/10.1101/2020.05.21.107565

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