Preexposure and Postexposure Prophylaxis of Rabies With Adeno-Associated Virus Expressing Virus-Neutralizing Antibody in Rodent Models

Fei Huang; Meishen Ren; Jie Pei; Hong Mei; Baokun Sui; Qiong Wu; Benjie Chai; Ruicheng Yang; Ming Zhou; Zhen F Fu; Huiping Zhou; Ling Zhao

doi:10.3389/fmicb.2021.702273

Preexposure and Postexposure Prophylaxis of Rabies With Adeno-Associated Virus Expressing Virus-Neutralizing Antibody in Rodent Models

Front Microbiol. 2021 Aug 19:12:702273. doi: 10.3389/fmicb.2021.702273. eCollection 2021.

Authors

Fei Huang^{1

2}, Meishen Ren^{1

2}, Jie Pei^{1

2}, Hong Mei^{1

2}, Baokun Sui^{1

2}, Qiong Wu^{1

2}, Benjie Chai^{1

2}, Ruicheng Yang^{1

2}, Ming Zhou^{1

2}, Zhen F Fu^{1

2}, Huiping Zhou³, Ling Zhao^{1

2}

Affiliations

¹ State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China.
² Key Laboratory of Preventive Veterinary Medicine in Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
³ School of Basic Medicine, Hubei University of Science and Technology, Xianning, China.

Abstract

Rabies, a fatal disease in humans and other mammals, is caused by the rabies virus (RABV), and it poses a public health threat in many parts of the world. Once symptoms of rabies appear, the mortality is near 100%. There is currently no effective treatment for rabies. In our study, two human-derived RABV-neutralizing antibodies (RVNA), CR57 and CR4098, were cloned into adeno-associated virus (AAV) vectors, and recombinant AAVs expressing RVNA were evaluated for postexposure prophylaxis after intrathecal injection into RABV-infected rats. At 4days post-infection with a lethal dose of RABV, 60% of the rats that received an intrathecal injection of AAV-CR57 survived, while 100% of the rats inoculated with AAV-enhanced green fluorescent protein (EGFP) succumbed to rabies. Overall, these results demonstrate that AAV-encoding RVNA can be utilized as a potential human rabies postexposure prophylaxis.

Keywords: adeno-associated virus; postexposure prophylaxis; preexposure prophylaxis; rabies viruses; rodent models; virus-neutralizing antibody.