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

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

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

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 alone for vaccination. To enhance antigen processing and cross-presentation in draining lymph nodes (DLNs), we developed an interferon (IFN)-armed RBD dimerized by an immunoglobulin fragment (I-R-F). I-R-F efficiently directs immunity against RBD to DLNs. A low dose of I-R-F induces not only high titers of long-lasting neutralizing antibodies (NAbs) but also more comprehensive T cell responses than RBD. Notably, I-R-F provides comprehensive protection in the form of a one-dose vaccine without an adjuvant. Our study shows that the pan-epitope modified human I-R-F (I-P-R-F) vaccine provides rapid and complete protection throughout the upper and lower respiratory tracts against a high-dose SARS-CoV-2 challenge in rhesus macaques. Based on these promising results, we have initiated a randomized, placebo-controlled, phase I/II trial of the human I-P-R-F vaccine (V-01) in 180 healthy adults, and the vaccine appears safe and elicits strong antiviral immune responses. Due to its potency and safety, this engineered vaccine may become a next-generation vaccine candidate in the global effort to overcome COVID-19.

Original languageEnglish (US)
Pages (from-to)1011-1023
Number of pages13
JournalCell Research
Volume31
Issue number9
DOIs
StatePublished - Sep 2021

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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