Interferon-armed RBD dimer enhances the immunogenicity of RBD for sterilizing immunity against SARS-CoV-2

Sun, S.; Cai, Y.; Song, T.-Z.; Pu, Y.; Cheng, L.; Xu, H.; Meng, C.; Lin, Y.; Sun, J.; Zhang, S.; Gao, Y.; Han, J.-B.; Feng, X.-L.; Yu, D.-D.; Zhu, Y.; Gao, P.; Tang, H.; Zhao, J.; Yang, J.; Hu, Z.; Zhang, Z.; Fu, Y.-X.; Zheng, Y.-T.; Peng, H.

doi:10.1101/2021.05.12.443228

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bioRxiv · 10.1101/2021.05.12.443228

Interferon-armed RBD dimer enhances the immunogenicity of RBD for sterilizing immunity against SARS-CoV-2

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Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global crisis, urgently necessitating the development of safe, efficacious, convenient-to-store, and low-cost vaccine options. A major challenge is that the receptor-binding domain (RBD)-only vaccine fails to trigger long-lasting protective immunity if used solely for vaccination. To enhance antigen processing and cross-presentation in draining lymph nodes (DLNs), we developed an interferon (IFN)-armed RBD dimerized by immunoglobulin fragment (I-R-F). I-R-F efficiently directs immunity against RBD to DLN. A low dose of I-R-F induces not only high titer long-lasting neutralizing antibodies but also comprehensive T cell responses than RBD, and even provides comprehensive protection in one dose without adjuvant. This study shows that the I-R-F vaccine provides rapid and complete protection throughout upper and lower respiratory tracts against high dose SARS-CoV-2 challenge in rhesus macaques. Due to its potency and safety, this engineered vaccine may become one of the next-generation vaccine candidates in the global race to defeat COVID-19.

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Sun, S., Cai, Y., Song, T.-Z., Pu, Y., Cheng, L., Xu, H., Meng, C., Lin, Y., Sun, J., Zhang, S., Gao, Y., Han, J.-B., Feng, X.-L., Yu, D.-D., Zhu, Y., Gao, P., Tang, H., Zhao, J., Yang, J., Hu, Z., Zhang, Z., Fu, Y.-X., Zheng, Y.-T., Peng, H.. 2021-05-12. Interferon-armed RBD dimer enhances the immunogenicity of RBD for sterilizing immunity against SARS-CoV-2. https://doi.org/10.1101/2021.05.12.443228

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