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

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

doi:10.1038/s41541-024-01059-9

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

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

Authors

Yiling Yang^#¹, Ruoke Wang^#¹, Fenglin Guo^#², Tian Zhao^#³, Yuqing Lei¹, Qianqian Yang¹, Yige Zeng¹, Ziqing Yang¹, Tatchapon Ajavavarakula¹, Ruijie Tan¹, Mingxi Li¹, Haodi Dong¹, Mengyue Niu¹, Keyan Bao¹, Hao Geng¹, Qining Lv¹, Qi Zhang¹, Xuanling Shi¹, Peng Liu^{4

5}, Jiwan Ge^{6

7}, Xinquan Wang⁸, Linqi Zhang^{9

10

11}

Affiliations

¹ Comprehensive AIDS Research Center, Pandemic Research Alliance Unit, Center for Infection Biology, School of Basic Medical Sciences, Tsinghua University, 100084, Beijing, China.
² 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.
³ School of Biomedical Engineering, Tsinghua University, 100084, Beijing, China.
⁴ School of Biomedical Engineering, Tsinghua University, 100084, Beijing, China. [email protected].
⁵ Changping Laboratory, 102206, Beijing, China. [email protected].
⁶ State Key Laboratory of Respiratory Health and Multimorbidity, National Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, 102629, Beijing, China. [email protected].
⁷ Key Laboratory of Pathogen Infection Prevention and Control (MOE), Ministry of Education, Chinese Academy of Medical Sciences & Peking Union Medical College, 102629, Beijing, China. [email protected].
⁸ 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. [email protected].
⁹ Comprehensive AIDS Research Center, Pandemic Research Alliance Unit, Center for Infection Biology, School of Basic Medical Sciences, Tsinghua University, 100084, Beijing, China. [email protected].
¹⁰ Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, 518055, Shenzhen, China. [email protected].
¹¹ Institute of Biomedical Health Technology and Engineering, Shenzhen Bay Laboratory, 518132, Shenzhen, China. [email protected].

^# Contributed equally.

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.

Abstract

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