Prophylactic efficacy of an intranasal spray with 2 synergetic antibodies neutralizing Omicron
作者全名：Zhang, Xinghai; Luo, Feiyang; Zhang, Huajun; Guo, Hangtian; Zhou, Junhui; Li, Tingting; Chen, Shaohong; Song, Shuyi; Shen, Meiying; Wu, Yan; Gao, Yan; Han, Xiaojian; Wang, Yingming; Hu, Chao; Zhao, Xiaodong; Guo, Huilin; Zhang, Dazhi; Lu, Yuchi; Wang, Wei; Wang, Kai; Tang, Ni; Jin, Tengchuan; Ding, Menglu; Luo, Shuhui; Lin, Cuicui; Lu, Tingting; Lu, Bingxia; Tian, Yang; Yang, Chengyong; Cheng, Guofeng; Yang, Haitao; Jin, Aishun; Ji, Xiaoyun; Gong, Rui; Chiu, Sandra; Huang, Ailong
作者地址：[Zhang, Xinghai; Zhang, Huajun; Zhou, Junhui; Chen, Shaohong; Wu, Yan; Gong, Rui] Chinese Acad Sci, Wuhan Inst Virol, Ctr Biosafety Mega Sci, CAS Key Lab Special Pathogens & Biosafety, Wuhan, Hubei, Peoples R China; [Luo, Feiyang; Li, Tingting; Song, Shuyi; Han, Xiaojian; Wang, Yingming; Hu, Chao; Jin, Aishun] Chongqing Med Univ, Coll Basic Med, Dept Immunol, Chongqing, Peoples R China; [Luo, Feiyang; Li, Tingting; Song, Shuyi; Han, Xiaojian; Wang, Yingming; Hu, Chao; Jin, Aishun] Chongqing Med Univ, Chongqing Key Lab Basic & Translat Res Tumor Immun, Chongqing, Peoples R China; [Guo, Hangtian; Ji, Xiaoyun] Nanjing Univ, Inst Viruses & Infect Dis, Sch Life Sci,State Key Lab Pharmaceut Biotechnol, Chem &Biomed Innovat Ctr ChemBIC,Inst Artificial I, Nanjing, Peoples R China; [Guo, Hangtian; Gao, Yan; Lu, Yuchi; Yang, Haitao] Shanghai Tech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai, Peoples R China; [Guo, Hangtian; Gao, Yan; Lu, Yuchi; Yang, Haitao] Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China; [Zhou, Junhui; Chen, Shaohong] Univ Chinese Acad Sci, Beijing, Peoples R China; [Shen, Meiying; Ding, Menglu] Chongqing Med Univ, Affiliated Hosp 1, Dept Endocrine Breast Surg, Chongqing, Peoples R China; [Gao, Yan; Yang, Haitao] Shanghai Clin Res & Trial Ctr, Shanghai, Peoples R China; [Zhao, Xiaodong; Guo, Huilin; Zhang, Dazhi] Chongqing Med Univ, Affiliated Hosp 2, Chongqing, Peoples R China; [Wang, Wei; Ji, Xiaoyun] Chongqing Med Univ, Inst Life Sci, Chongqing, Peoples R China; [Wang, Kai; Tang, Ni; Cheng, Guofeng; Yang, Haitao; Jin, Aishun; Ji, Xiaoyun; Gong, Rui; Chiu, Sandra; Huang, Ailong] Chongqing Med Univ, Affiliated Hosp 2, Inst Viral Hepatitis, Key Lab Mol Biol Infect Dis,Minist Educ,Dept Infec, Chongqing, Peoples R China; [Jin, Tengchuan; Chiu, Sandra] Univ Sci & Technol China, Div Life Sci & Med, Hefei, Anhui, Peoples R China; [Li, Tingting; Ding, Menglu; Luo, Shuhui; Lin, Cuicui; Lu, Bingxia; Tian, Yang; Yang, Chengyong; Cheng, Guofeng] Mindao Haoyue Co Ltd, Chongqing, Peoples R China; [Ji, Xiaoyun] Minist Educ, Engn Res Ctr Prot & Peptide Med, Nanjing, Peoples R China
通信作者：Gong, R (通讯作者)，Chinese Acad Sci, Wuhan Inst Virol, Ctr Biosafety Mega Sci, CAS Key Lab Special Pathogens & Biosafety, Wuhan, Hubei, Peoples R China.; Cheng, GF; Yang, HT; Jin, AS; Ji, XY; Gong, R; Chiu, S; Huang, AL (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Inst Viral Hepatitis, Key Lab Mol Biol Infect Dis,Minist Educ,Dept Infec, Chongqing, Peoples R China.
来源：JCI INSIGHT
ESI学科分类：CLINICAL MEDICINE
WOS号：WOS:001201898800001
JCR分区：Q1
影响因子：6.3
年份：2024
卷号：9
期号：7
开始页：
结束页：
文献类型：Article
关键词：
摘要：BACKGROUND. As Omicron is prompted to replicate in the upper airway, neutralizing antibodies (NAbs) delivered through inhalation might inhibit early -stage infection in the respiratory tract. Thus, elucidating the prophylactic efficacy of NAbs via nasal spray addresses an important clinical need. METHODS. The applicable potential of a nasal spray cocktail containing 2 NAbs was characterized by testing its neutralizing potency, synergetic neutralizing mechanism, emergency protective and therapeutic efficacy in a hamster model, and pharmacokinetics/pharmacodynamic (PK/PD) in human nasal cavity. RESULTS. The 2 NAbs displayed broad neutralizing efficacy against Omicron, and they could structurally compensate each other in blocking the Spike-ACE2 interaction. When administrated through the intranasal mucosal route, this cocktail demonstrated profound efficacy in the emergency prevention in hamsters challenged with authentic Omicron BA.1. The investigatorinitiated trial in healthy volunteers confirmed the safety and the PK/PD of the NAb cocktail delivered via nasal spray. Nasal samples from the participants receiving 4 administrations over a course of 16 hours demonstrated potent neutralization against Omicron BA.5 in an ex vivo pseudovirus neutralization assay. CONCLUSION. These results demonstrate that the NAb cocktail nasal spray provides a good basis for clinical prophylactic efficacy against Omicron infections.
基金机构：National Science and Technology Major Project [2017ZX10202203]; National Key Research and Development Program of China [2018YFA0507100]; Guangzhou National Laboratory [SRPG22-015]; Lingang Laboratory [LG202101-01-07]; Science and Technology Commission of Shanghai Municipality [YDZX20213100001556]; Emergency Project from the Science & Technology Commission of Chongqing [cstc2021jscx-fyzxX0001]
基金资助正文：The National Science and Technology Major Project (2017ZX10202203) , the National Key Research and Development Program of China (2018YFA0507100) , Guangzhou National Laboratory (SRPG22-015) , Lingang Laboratory (LG202101-01-07) , Science and Technology Commission of Shanghai Municipality (YDZX20213100001556) , and the Emergency Project from the Science & Technology Commission of Chongqing (cstc2021jscx-fyzxX0001) .
