Nasal delivery of secretory IgA confers enhanced neutralizing activity against Omicron variants compared to its IgG counterpart.

IF 12.1 1区医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Molecular Therapy Pub Date : 2025-03-01 DOI:10.1016/j.ymthe.2025.02.041

Guanying Zhang, Ping Huang, Hongyu Yuan, Entao Li, Xiangyang Chi, Hancong Sun, Jin Han, Ting Fang, Yunzhu Dong, Jie Li, Yaoxing Wang, Jianmin Li, Sandra Chiu, Changming Yu

{"title":"Nasal delivery of secretory IgA confers enhanced neutralizing activity against Omicron variants compared to its IgG counterpart.","authors":"Guanying Zhang, Ping Huang, Hongyu Yuan, Entao Li, Xiangyang Chi, Hancong Sun, Jin Han, Ting Fang, Yunzhu Dong, Jie Li, Yaoxing Wang, Jianmin Li, Sandra Chiu, Changming Yu","doi":"10.1016/j.ymthe.2025.02.041","DOIUrl":null,"url":null,"abstract":"<p><p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its multiple variants continue to spread worldwide, causing respiratory symptoms primarily through mucosal infection. The mucosa serves as the primary barrier against viral entry, in which secretory immunoglobulin A (sIgA) plays a critical role in preventing infection. Here, we engineered and characterized a neutralizing monoclonal antibody, ZW2G10, in IgG, monomeric, dimeric, secretory IgA1, and IgA2 formats. All seven forms of the ZW2G10 antibody showed similar thermal stability. sIgA, especially sIgA1, displayed enhanced neutralizing activity against Omicron-lineage BA.2.75, BA.2.76 and BA.4/5 pseudoviruses compared to IgG. Nasal administration of sIgA1 conferred robust protection against the BA.2.76 pseudovirus in ACE2 transgenic mice, and its protective efficacy was superior to that of IgG. The crystal structure of Omicron receptor binding domain (RBD) and ZW2G10 antibody fragment (Fab) complex revealed that ZW2G10 had no clashes with ACE2. Thus, nasal administration of sIgA may serve as a promising tool for the prevention and treatment of Omicron infection.</p>","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":""},"PeriodicalIF":12.1000,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ymthe.2025.02.041","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its multiple variants continue to spread worldwide, causing respiratory symptoms primarily through mucosal infection. The mucosa serves as the primary barrier against viral entry, in which secretory immunoglobulin A (sIgA) plays a critical role in preventing infection. Here, we engineered and characterized a neutralizing monoclonal antibody, ZW2G10, in IgG, monomeric, dimeric, secretory IgA1, and IgA2 formats. All seven forms of the ZW2G10 antibody showed similar thermal stability. sIgA, especially sIgA1, displayed enhanced neutralizing activity against Omicron-lineage BA.2.75, BA.2.76 and BA.4/5 pseudoviruses compared to IgG. Nasal administration of sIgA1 conferred robust protection against the BA.2.76 pseudovirus in ACE2 transgenic mice, and its protective efficacy was superior to that of IgG. The crystal structure of Omicron receptor binding domain (RBD) and ZW2G10 antibody fragment (Fab) complex revealed that ZW2G10 had no clashes with ACE2. Thus, nasal administration of sIgA may serve as a promising tool for the prevention and treatment of Omicron infection.

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

Molecular Therapy 医学-生物工程与应用微生物

CiteScore

19.20

自引率

3.20%

发文量

357

审稿时长

3 months

期刊介绍： Molecular Therapy is the leading journal for research in gene transfer, vector development, stem cell manipulation, and therapeutic interventions. It covers a broad spectrum of topics including genetic and acquired disease correction, vaccine development, pre-clinical validation, safety/efficacy studies, and clinical trials. With a focus on advancing genetics, medicine, and biotechnology, Molecular Therapy publishes peer-reviewed research, reviews, and commentaries to showcase the latest advancements in the field. With an impressive impact factor of 12.4 in 2022, it continues to attract top-tier contributions.