Single dose recombinant VSV based vaccine elicits robust and durable neutralizing antibody against Hantaan virus.
Hui Zhang, He Liu, Jing Wei, Yamei Dang, Yuan Wang, Qiqi Yang, Liang Zhang, Chuantao Ye, Bin Wang, Xiaolei Jin, Linfeng Cheng, Hongwei Ma, Yangchao Dong, Yinghui Li, Yinlan Bai, Xin Lv, Yingfeng Lei, Zhikai Xu, Wei Ye, Fanglin Zhang
Author Information
Hui Zhang: Department of Microbiology, School of Preclinical Medicine, Airforce Medical University: Fourth Military Medical University, Xi' an, Shaanxi, China.
He Liu: Department of Microbiology, School of Preclinical Medicine, Airforce Medical University: Fourth Military Medical University, Xi' an, Shaanxi, China.
Jing Wei: Department of Microbiology, School of Preclinical Medicine, Airforce Medical University: Fourth Military Medical University, Xi' an, Shaanxi, China.
Yamei Dang: Department of Microbiology, School of Preclinical Medicine, Airforce Medical University: Fourth Military Medical University, Xi' an, Shaanxi, China.
Yuan Wang: Department of Microbiology, School of Preclinical Medicine, Airforce Medical University: Fourth Military Medical University, Xi' an, Shaanxi, China.
Qiqi Yang: Department of Microbiology, School of Preclinical Medicine, Airforce Medical University: Fourth Military Medical University, Xi' an, Shaanxi, China.
Liang Zhang: Department of Microbiology, School of Preclinical Medicine, Airforce Medical University: Fourth Military Medical University, Xi' an, Shaanxi, China.
Chuantao Ye: Department of Microbiology, School of Preclinical Medicine, Airforce Medical University: Fourth Military Medical University, Xi' an, Shaanxi, China.
Bin Wang: Center of Clinical Aerospace Medicine, Airforce Medical University: Fourth Military Medical University, Xi' an, Shaanxi, China.
Xiaolei Jin: Student Brigade, School of Preclinical Medicine, Airforce Medical University: Fourth Military Medical University, Xi' an, Shaanxi, China.
Linfeng Cheng: Department of Microbiology, School of Preclinical Medicine, Airforce Medical University: Fourth Military Medical University, Xi' an, Shaanxi, China.
Hongwei Ma: Department of Microbiology, School of Preclinical Medicine, Airforce Medical University: Fourth Military Medical University, Xi' an, Shaanxi, China.
Yangchao Dong: Department of Microbiology, School of Preclinical Medicine, Airforce Medical University: Fourth Military Medical University, Xi' an, Shaanxi, China.
Yinghui Li: Department of Microbiology, School of Preclinical Medicine, Airforce Medical University: Fourth Military Medical University, Xi' an, Shaanxi, China.
Yinlan Bai: Department of Microbiology, School of Preclinical Medicine, Airforce Medical University: Fourth Military Medical University, Xi' an, Shaanxi, China.
Xin Lv: Department of Microbiology, School of Preclinical Medicine, Airforce Medical University: Fourth Military Medical University, Xi' an, Shaanxi, China.
Yingfeng Lei: Department of Microbiology, School of Preclinical Medicine, Airforce Medical University: Fourth Military Medical University, Xi' an, Shaanxi, China.
Zhikai Xu: Department of Microbiology, School of Preclinical Medicine, Airforce Medical University: Fourth Military Medical University, Xi' an, Shaanxi, China. zhikaixu@fmmu.edu.cn.
Wei Ye: Department of Microbiology, School of Preclinical Medicine, Airforce Medical University: Fourth Military Medical University, Xi' an, Shaanxi, China. virologyyw@fmmu.edu.cn. ORCID
Fanglin Zhang: Department of Microbiology, School of Preclinical Medicine, Airforce Medical University: Fourth Military Medical University, Xi' an, Shaanxi, China. flzhang@fmmu.edu.cn.
Hantaan virus (HTNV) is a pathogenic orthohantavirus prevalent in East Asia that is known to cause hemorrhagic fever with severe renal syndrome (HFRS), which has a high fatality rate. However, a Food and Drug Administration (FDA)-approved vaccine is not currently available against this virus. Although inactivated vaccines have been certified and used in endemic regions for decades, the neutralizing antibody (NAb) titer induced by inactivated vaccines is low and the immunization schedule is complicated, requiring at least three injections spanning approximately 6 months to 1 year. Replication-competent vesicular stomatitis virus (VSV)-based vaccines provide prolonged protection after a single injection. In this study, we successfully engineered the HTNV glycoprotein (GP) in the VSV genome by replacing the VSV-G open reading frame. The resulting recombinant (r) rVSV-HTNV-GP was rescued, and the immunogenicity of GP was similar to that of HTNV. BALB/c mice immunized with rVSV-HTNV-GP showed a high titer of NAb against HTNV after a single injection. Notably, the cross-reactive NAb response induced by rVSV-HTNV-GP against Seoul virus (an orthohantavirus) was higher than that induced by three sequential injections of inactivated vaccines. Upon challenge with HTNV, rVSV-HTNV-GP-immunized mice showed a profoundly reduced viral burden in multiple tissues, and inflammation in the lungs and liver was nearly undetectable. Moreover, a single injection of rVSV-HTNV-GP established a prolonged immunological memory status as the NAbs were sustained for over 1 year and provided long-term protection against HTNV infection. The findings of our study can support further development of an rVSV-HTNV-GP-based HTNV vaccine with a simplified immunization schedule.
References
Int J Infect Dis. 2023 Sep;134:95-98
[PMID: 37247691]
