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

Autor: Pu Gao, Chaoyang Meng, Hua Peng, Yifan Lin, Yang Pu, Fang Zhao, Yang Xin Fu, Yueqi Cai, Haibin Huang, Tian-Zhang Song, Yu Gao, Zhenxiang Hu, Silin Zhang, Jing Sun, Hairong Xu, Yalan Zhu, Lin Cheng, Dan-Dan Yu, Yong-Tang Zheng, Jian-Bao Han, Shiyu Sun, Xiao-Li Feng, Zheng Zhang, Haidong Tang, Jincun Zhao, Jiaming Yang
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Cell Research
ISSN: 1748-7838
1001-0602
Popis: 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.
Databáze: OpenAIRE
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