当前位置: X-MOL 学术Cell Res. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Interferon-armed RBD dimer enhances the immunogenicity of RBD for sterilizing immunity against SARS-CoV-2
Cell Research ( IF 28.1 ) Pub Date : 2021-07-15 , DOI: 10.1038/s41422-021-00531-8
Shiyu Sun 1, 2 , Yueqi Cai 1, 2 , Tian-Zhang Song 3 , Yang Pu 4 , Lin Cheng 5 , Hairong Xu 1 , Jing Sun 6 , Chaoyang Meng 1 , Yifan Lin 1, 2 , Haibin Huang 7 , Fang Zhao 7 , Silin Zhang 8 , Yu Gao 2, 9 , Jian-Bao Han 10 , Xiao-Li Feng 10 , Dan-Dan Yu 3 , Yalan Zhu 1 , Pu Gao 1 , Haidong Tang 8 , Jincun Zhao 6 , Zheng Zhang 5 , Jiaming Yang 7 , Zhenxiang Hu 7 , Yang-Xin Fu 11 , Yong-Tang Zheng 3, 10, 12 , Hua Peng 1, 12
Affiliation  

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.



中文翻译:

干扰素武装的 RBD 二聚体增强 RBD 的免疫原性以消除针对 SARS-CoV-2 的免疫力

严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 已引发全球危机,迫切需要开发安全、有效、便于储存和低成本的疫苗选择。一个主要挑战是,如果单独用于疫苗接种,仅受体结合域 (RBD) 疫苗无法触发持久的保护性免疫。为了增强引流淋巴结 (DLN) 中的抗原处理和交叉呈递,我们开发了一种由免疫球蛋白片段 (IRF) 二聚化的干扰素 (IFN) 臂 RBD。IRF 有效地将针对 RBD 的免疫力引导至 DLN。低剂量的 IRF 不仅可以诱导高效价的长效中和抗体 (NAb),还可以诱导比 RBD 更全面的 T 细胞反应。值得注意的是,IRF 以无佐剂的单剂疫苗形式提供全面保护。我们的研究表明,泛表位修饰的人类 IRF (IPRF) 疫苗可在整个上呼吸道和下呼吸道提供快速和全面的保护,以抵抗恒河猴高剂量 SARS-CoV-2 的攻击。基于这些有希望的结果,我们在 180 名健康成人中启动了人 IPRF 疫苗 (V-01) 的随机、安慰剂对照、I/II 期试验,该疫苗似乎是安全的并引发强烈的抗病毒免疫反应。由于其效力和安全性,这种工程疫苗可能成为全球抗击 COVID-19 的下一代候选疫苗。我们已经在 180 名健康成年人中启动了人类 IPRF 疫苗 (V-01) 的随机、安慰剂对照的 I/II 期试验,该疫苗似乎是安全的,并引发了强烈的抗病毒免疫反应。由于其效力和安全性,这种工程疫苗可能成为全球抗击 COVID-19 的下一代候选疫苗。我们已经在 180 名健康成年人中启动了人类 IPRF 疫苗 (V-01) 的随机、安慰剂对照的 I/II 期试验,该疫苗似乎是安全的,并引发了强烈的抗病毒免疫反应。由于其效力和安全性,这种工程疫苗可能成为全球抗击 COVID-19 的下一代候选疫苗。

更新日期:2021-07-16
down
wechat
bug