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

Sun, Shiyu; Cai, Yueqi; Song, Tian-Zhang; Pu, Yang; Cheng, Lin; Xu, Hairong; Meng, Chaoyang; Lin, Yifan; Sun, Jing; Zhang, Silin; Gao, Yu; Han, Jian-Bao; Feng, Xiao-Li; Yu, Dan-Dan; Zhu, Yalan; Gao, Pu; Tang, Haidong; Zhao, Jincun; Zhang, Zheng; Yang, Jiaming; Hu, Zenxiang; Fu, Yang-Xin; Zheng, Yong-Tang; Peng, Hua

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.