DS2设计型预融合F疫苗可诱导针对呼吸道合胞病毒感染产生强烈且具有保护性的抗体反应。

DS2 designer pre-fusion F vaccine induces strong and protective antibody response against RSV infection.

作者信息

Yang Yiling, Wang Ruoke, Guo Fenglin, Zhao Tian, Lei Yuqing, Yang Qianqian, Zeng Yige, Yang Ziqing, Ajavavarakula Tatchapon, Tan Ruijie, Li Mingxi, Dong Haodi, Niu Mengyue, Bao Keyan, Geng Hao, Lv Qining, Zhang Qi, Shi Xuanling, Liu Peng, Ge Jiwan, Wang Xinquan, Zhang Linqi

机构信息

Comprehensive AIDS Research Center, Pandemic Research Alliance Unit, Center for Infection Biology, School of Basic Medical Sciences, Tsinghua University, 100084, Beijing, China.

The Ministry of Education Key Laboratory of Protein Science, Beijing Frontier Research Center for Biological Structure, School of Life Sciences, Tsinghua University, 100084, Beijing, China.

出版信息

NPJ Vaccines. 2024 Dec 31;9(1):258. doi: 10.1038/s41541-024-01059-9.

DOI:10.1038/s41541-024-01059-9

PMID:39741146

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11688450/

Abstract

DS-Cav1, SC-TM, and DS2 are distinct designer pre-fusion F proteins (pre-F) of respiratory syncytial virus (RSV) developed for vaccines. However, their immunogenicity has not been directly compared. In this study, we generated three recombinant vaccines using the chimpanzee adenovirus vector AdC68 to express DS-Cav1, SC-TM, and DS2. All three vaccines elicited robust serum binding and neutralizing antibodies following intramuscular priming and boosting. DS2 induced the strongest antibody responses, followed by SC-TM and DS-Cav1. DS2 also provided strong protection against live RSV challenge. Monoclonal antibodies (mAbs) isolated from long-lived antibody-secreting cells (ASCs) in the bone marrow six months post-immunization with AdC68-DS2 predominantly targeted site Ø as well as site II. One neutralizing antibody against site II, mAb60, conferred strong protection against live RSV infection in mice. These findings highlight the strong ability of the DS2 design in eliciting long-lived antibody responses and guide the development of next-generation RSV vaccines.

摘要

DS-Cav1、SC-TM和DS2是为疫苗研发的呼吸道合胞病毒（RSV）不同的设计前融合F蛋白（前F）。然而，它们的免疫原性尚未得到直接比较。在本研究中，我们使用黑猩猩腺病毒载体AdC68构建了三种重组疫苗，分别表达DS-Cav1、SC-TM和DS2。这三种疫苗在肌肉注射初次免疫和加强免疫后均引发了强烈的血清结合抗体和中和抗体。DS2诱导的抗体反应最强，其次是SC-TM和DS-Cav1。DS2还对活RSV攻击提供了强大的保护作用。在接种AdC68-DS2六个月后，从骨髓中长寿命抗体分泌细胞（ASC）分离出的单克隆抗体（mAb）主要靶向位点Ø以及位点II。一种针对位点II的中和抗体mAb60对小鼠活RSV感染提供了强大的保护作用。这些发现突出了DS2设计在引发长寿命抗体反应方面的强大能力，并为下一代RSV疫苗的研发提供了指导。