tetano
Editor, Senior Moderator
Cell Res
. 2021 Jul 15.
doi: 10.1038/s41422-021-00531-8. Online ahead of print.
Interferon-armed RBD dimer enhances the immunogenicity of RBD for sterilizing immunity against SARS-CoV-2
Shiyu Sun[SUP] #[/SUP][SUP] 1 2 [/SUP], Yueqi Cai[SUP] #[/SUP][SUP] 1 2 [/SUP], Tian-Zhang Song[SUP] #[/SUP][SUP] 3 [/SUP], Yang Pu[SUP] #[/SUP][SUP] 4 [/SUP], Lin Cheng[SUP] 5 [/SUP], Hairong Xu[SUP] 1 [/SUP], Jing Sun[SUP] 6 [/SUP], Chaoyang Meng[SUP] 1 [/SUP], Yifan Lin[SUP] 1 2 [/SUP], Haibin Huang[SUP] 7 [/SUP], Fang Zhao[SUP] 7 [/SUP], Silin Zhang[SUP] 8 [/SUP], Yu Gao[SUP] 2 9 [/SUP], Jian-Bao Han[SUP] 10 [/SUP], Xiao-Li Feng[SUP] 10 [/SUP], Dan-Dan Yu[SUP] 3 [/SUP], Yalan Zhu[SUP] 1 [/SUP], Pu Gao[SUP] 1 [/SUP], Haidong Tang[SUP] 8 [/SUP], Jincun Zhao[SUP] 6 [/SUP], Zheng Zhang[SUP] 5 [/SUP], Jiaming Yang[SUP] 7 [/SUP], Zhenxiang Hu[SUP] 7 [/SUP], Yang-Xin Fu[SUP] 11 [/SUP], Yong-Tang Zheng[SUP] 12 13 14 [/SUP], Hua Peng[SUP] 15 16 [/SUP]
Affiliations
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.
. 2021 Jul 15.
doi: 10.1038/s41422-021-00531-8. Online ahead of print.
Interferon-armed RBD dimer enhances the immunogenicity of RBD for sterilizing immunity against SARS-CoV-2
Shiyu Sun[SUP] #[/SUP][SUP] 1 2 [/SUP], Yueqi Cai[SUP] #[/SUP][SUP] 1 2 [/SUP], Tian-Zhang Song[SUP] #[/SUP][SUP] 3 [/SUP], Yang Pu[SUP] #[/SUP][SUP] 4 [/SUP], Lin Cheng[SUP] 5 [/SUP], Hairong Xu[SUP] 1 [/SUP], Jing Sun[SUP] 6 [/SUP], Chaoyang Meng[SUP] 1 [/SUP], Yifan Lin[SUP] 1 2 [/SUP], Haibin Huang[SUP] 7 [/SUP], Fang Zhao[SUP] 7 [/SUP], Silin Zhang[SUP] 8 [/SUP], Yu Gao[SUP] 2 9 [/SUP], Jian-Bao Han[SUP] 10 [/SUP], Xiao-Li Feng[SUP] 10 [/SUP], Dan-Dan Yu[SUP] 3 [/SUP], Yalan Zhu[SUP] 1 [/SUP], Pu Gao[SUP] 1 [/SUP], Haidong Tang[SUP] 8 [/SUP], Jincun Zhao[SUP] 6 [/SUP], Zheng Zhang[SUP] 5 [/SUP], Jiaming Yang[SUP] 7 [/SUP], Zhenxiang Hu[SUP] 7 [/SUP], Yang-Xin Fu[SUP] 11 [/SUP], Yong-Tang Zheng[SUP] 12 13 14 [/SUP], Hua Peng[SUP] 15 16 [/SUP]
Affiliations
- PMID: 34267349
- DOI: 10.1038/s41422-021-00531-8
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.