Generation and Effect Testing of a SARS-CoV-2 RBD-Targeted Polyclonal Therapeutic Antibody Based on a 2-D Airway Organoid Screening System

He, Yunjiao1; Qu, Jing2; Wei, Lan2,3; Liao, Shumin2,4,5; Zheng, Nianzhen2,6,7; Liu, Yingzi2; Wang, Xingyun1; Jing, Yue8,9; Shen, Clifton Kwang-Fu8,9; Ji, Chong8; Luo, Guxun9; Zhang, Yiyun10; Xiang, Qi1; Fu, Yang1; Li, Shuo11,12; Fan, Yunping5; Fang, Shisong13; Wang, Peng1; Li, Liang2

2021-10-18

10.3389/fimmu.2021.689065

Frontiers in Immunology   影响因子和分区

1664-3224

Coronavirus disease 2019 (COVID-19) is an acute respiratory infectious disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The US FDA has approved several therapeutics and vaccines worldwide through the emergency use authorization in response to the rapid spread of COVID-19. Nevertheless, the efficacies of these treatments are being challenged by viral escape mutations. There is an urgent need to develop effective treatments protecting against SARS-CoV-2 infection and to establish a stable effect-screening model to test potential drugs. Polyclonal antibodies (pAbs) have an intrinsic advantage in such developments because they can target rapidly mutating viral strains as a result of the complexity of their binding epitopes. In this study, we generated anti-receptor-binding domain (anti-RBD) pAbs from rabbit serum and tested their safety and efficacy in response to SARS-CoV-2 infection both in vivo and ex vivo. Primary human bronchial epithelial two-dimensional (2-D) organoids were cultured and differentiated to a mature morphology and subsequently employed for SARS-CoV-2 infection and drug screening. The pAbs protected the airway organoids from viral infection and tissue damage. Potential side effects were tested in mouse models for both inhalation and vein injection. The pAbs displayed effective viral neutralization effects without significant side effects. Thus, the use of animal immune serum-derived pAbs might be a potential therapy for protection against SARS-CoV-2 infection, with the strategy developed to produce these pAbs providing new insight into the treatment of respiratory tract infections, especially for infections with viruses undergoing rapid mutation.

SARS-CoV-2 viral infection polyclonal antibody airway organoids receptor-binding domain

SCI

英语

第一 ; 通讯

Immunology

Immunology

WOS:000715735100001

FRONTIERS MEDIA SA

Web of Science

1.Southern Univ Sci & Technol, Sch Med, Shenzhen, Peoples R China
2.Chinese Acad Sci, Inst Biomed & Biotechnol, Shenzhen Inst Adv Technol, Shenzhen, Peoples R China
3.Univ Newcastle, Fac Hlth & Med, Sch Biomed Sci & Pharm, Hunter Med Res Inst, New Lambton Hts, NSW, Australia
4.Sun Yat Sen Univ, Dept Thorac Surg, Affiliated Hosp 7, Shenzhen, Peoples R China
5.Sun Yat Sen Univ, Dept Otolaryngol, Affiliated Hosp 7, Shenzhen, Peoples R China
6.Sun Yat Sen Univ, Dept Otorhinolaryngol Head Neck Surg, Affiliated Hosp 1, Guangzhou, Peoples R China
7.Guangzhou Key Lab Otorhinolaryngol, Guangzhou, Peoples R China
8.Jiangxi Inst Biol Prod Co Ltd, Dept Res & Dev Dept, Jian, Jiangxi, Peoples R China
9.Jiangxi Inst Biol Prod Shenzhen R&D Ctr Co Ltd, Dept Res & Dev, Shenzhen, Peoples R China
10.Hainan Inst Pharmaceut Res Co Ltd, Dept Res & Dev, Haikou, Hainan, Peoples R China
11.Huazhong Univ Sci & Technol, Dept Otolaryngol, Union Shenzhen Hosp, Shenzhen, Peoples R China
12.Shenzhen Univ, Dept Otolaryngol, Hlth Sci Ctr, Affiliated Hosp 6, Shenzhen, Peoples R China
13.Shenzhen Ctr Dis Control & Prevent, Dept Pathogen Biol, Shenzhen, Peoples R China

He, Yunjiao,Qu, Jing,Wei, Lan,et al. Generation and Effect Testing of a SARS-CoV-2 RBD-Targeted Polyclonal Therapeutic Antibody Based on a 2-D Airway Organoid Screening System[J]. Frontiers in Immunology,2021,12.

He, Yunjiao.,Qu, Jing.,Wei, Lan.,Liao, Shumin.,Zheng, Nianzhen.,...&Li, Liang.(2021).Generation and Effect Testing of a SARS-CoV-2 RBD-Targeted Polyclonal Therapeutic Antibody Based on a 2-D Airway Organoid Screening System.Frontiers in Immunology,12.

He, Yunjiao,et al."Generation and Effect Testing of a SARS-CoV-2 RBD-Targeted Polyclonal Therapeutic Antibody Based on a 2-D Airway Organoid Screening System".Frontiers in Immunology 12(2021).