A protective human antibody against respiratory syncytial virus by targeting a prefusion epitope across sites IV and V of the viral fusion glycoprotein  

作　　者：Lianpan Dai Jian Song Lili Xu Zhao Gao Senyu Xu Yan Chai Liang Wang Mi Yang Tong Ma Qihui Wang Sushan Cao Junming Yie Gang Zou Zhengde Xie Jim Zhen Wu George Fu Gao 

机构地区：[1]CAS Key Laboratory of Pathogen Microbiology and Immunology,Institute of Microbiology,Chinese Academy of Sciences,Beijing,China [2]Key Laboratory of Major Diseases in Children,Ministry of Education,National Clinical Research Center for Respiratory Diseases,Beijing Key Laboratory of Pediatric Respiratory Infection Diseases,Research Unit of Critical Infection in Children,Chinese Academy of Medical Sciences,2019RU016,Laboratory of Infection and Virology,Beijing Pediatric Research Institute,Beijing Children’s Hospital,Capital Medical University,National Center for Children’s Health,Beijing,China [3]Shanghai Ark Biopharmaceutical Co.,Ltd.,Shanghai,China [4]Savaid Medical School,University of Chinese Academy of Sciences,Beijing,China

出　　处：《hLife》2023年第1期12-25,共14页健康科学（英文）

基　　金：supported by the National Natural Science Foundation of China(NSFC)(81991494 and 82122031);the National Key R&D Program of China(2020YFA0907100);the Chinese Academy of Sciences(YSBR-010);the CAMS Innovation Fund for Medical Sciences(CIFMS)(2019-I2M-5-026);Beijing Natural Science Foundation(L222076);L.D.is supported by the Youth Innovation Promotion Association CAS,China(2018113).

摘　　要：Respiratory syncytial virus(RSV)is one of the leading pathogens that cause lower respiratory tract infections in infants and the elderly.Passive immunoprophylaxis with monoclonal antibody(mAb)has been approved to prevent morbidity and mortality from RSV infection in infants.Here we report the isolation of two neutralizing mAbs against RSV from convalescent children by prefusion form of fusion(F)glycoprotein as bait.One mAb RV11 exhibited good potency in neutralization of RSV strains from both A and B subtypes in cell-based assay,and protected mice from RSV infection in vivo.An RV11 escape mutant was identified,which contains an S443P mutation in F protein.Crystal structure showed the RV11 bound to a conserved prefusion epitope across the antigenic sites IV and V of the F glycoprotein.RV11 showed a strong synergistic effect when combined with two RSV antivirals,an F-targeting small molecular inhibitor ziresovir and a siteØneutralizing mAb D25(the parental mAb for nirsevimab).The study extended our knowledge to the neutralizing and protective epitopes of RSV,and the mAb RV11 deserves further development for clinical translation.

关 键 词：Respiratory syncytial virus(RSV)antibody RSV monoclonal antibody RSV fusion glycoprotein RSV epitope PALIVIZUMAB RSV prophylaxis 

分 类 号：R56[医药卫生—呼吸系统]