Volume 31, No 9, Sep 2021

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 31 Issue 9, September 2021: 1011-1023   |  Open Access

ORIGINAL ARTICLES

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

Shiyu Sun^1,2,† , Yueqi Cai^1,2,† , Tian-Zhang Song^3,† , Yang Pu^4,† , Lin Cheng⁵ , Hairong Xu¹ , Jing Sun⁶ , Chaoyang Meng¹ , Yifan Lin^1,2 , Haibin Huang⁷ , Fang Zhao⁷ , Silin Zhang⁸ , Yu Gao^2,9 , Jian-Bao Han¹⁰ , Xiao-Li Feng¹⁰ , Dan-Dan Yu³ , Yalan Zhu¹ , Pu Gao¹ , Haidong Tang⁸ , Jincun Zhao⁶ , Zheng Zhang⁵ , Jiaming Yang⁷ , Zhenxiang Hu⁷ , Yang-Xin Fu^11,* , Yong-Tang Zheng^3,10,12,* , Hua Peng^1,12,*

¹Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
²University of Chinese Academy of Sciences, Beijing, China
³Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China
⁴Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, China
⁵Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People’s Hospital, Shenzhen, Guangdong Province, China
⁶State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
⁷LivzonBio, Inc., Zhuhai, Guangdong, China
⁸School of Pharmaceutical Sciences, Tsinghua University, Beijing, China
⁹Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
¹⁰Kunming National High-level Biosafety Research Center for Non-human Primates, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China
¹¹Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA
¹²Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), and Guangzhou Laboratory, Guangzhou, China
^†These authors contributed equally: Shiyu Sun, Yueqi Cai, Tian-Zhang Song, Yang Pu
Correspondence: Yang-Xin Fu(Yang-Xin.Fu@UTSouthwestern.edu)Yong-Tang Zheng(zhengyt@mail.kiz.ac.cn)Hua Peng(hpeng@moon.ibp.cas.cn)

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.

https://doi.org/10.1038/s41422-021-00531-8

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