Exacerbated lung inflammation in offspring with high maternal antibody levels following secondary RSV exposure

作者全名：Ma, Jinhua; Gong, Ting; Luo, Tingting; Li, Shuanglian; Zhong, Li; Zhao, Xin; Mei, Chenghao; Bu, Huaqin; Jia, Zhenxing; Kuang, Xiaohu; Wang, Xiaoli; Fu, Zhou; Tian, Daiyin

作者地址：[Ma, Jinhua; Gong, Ting; Luo, Tingting; Li, Shuanglian; Zhong, Li; Zhao, Xin; Mei, Chenghao; Bu, Huaqin; Fu, Zhou; Tian, Daiyin] Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Dept Resp Med,Chongqing Key Lab Child Rare Dis Inf, Minist Educ,Key Lab Child Dev & Disorders,Children, Chongqing, Peoples R China; [Jia, Zhenxing; Kuang, Xiaohu; Wang, Xiaoli] Zhuhai Trinomab Pharmaceut Co Ltd, Dept mAbs Discovery, Zhuhai, Peoples R China; [Tian, Daiyin] Chongqing Med Univ, Yibin Hosp, Dept Resp Med, Childrens Hosp, Yibin, Peoples R China

通信作者：Tian, DY (通讯作者)，Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Dept Resp Med,Chongqing Key Lab Child Rare Dis Inf, Minist Educ,Key Lab Child Dev & Disorders,Children, Chongqing, Peoples R China.; Tian, DY (通讯作者)，Chongqing Med Univ, Yibin Hosp, Dept Resp Med, Childrens Hosp, Yibin, Peoples R China.

来源：FRONTIERS IN IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:001220562200001

JCR分区：Q1

影响因子：5.7

年份：2024

卷号：15

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：respiratory syncytial virus; maternal immunization; secondary RSV exposure; mucosal immunity; type 2 inflammation

摘要：Respiratory syncytial virus (RSV) is the primary cause of bronchiolitis-related hospitalizations among children under 5 years of age, with reinfection being common throughout life. Maternal vaccination has emerged as a promising strategy, delivering elevated antibody levels to newborns for immediate protection. However, limited research has explored the protective efficacy of maternal antibodies (matAbs) against secondary RSV infections in offspring. To address this gap, we employed a mouse model of maternal RSV vaccination and secondary infection of offspring to evaluate lung pathology following RSV reinfection in mice with varying levels of maternal antibody (matAb). Additionally, we aimed to investigate the potential causes of exacerbated lung inflammation in offspring with high matAb levels following secondary RSV exposure. Our findings revealed that offspring with elevated levels of maternal pre-F antibody demonstrated effective protection against lung pathology following the initial RSV infection. However, this protection was compromised upon reinfection, manifesting as heightened weight loss, exacerbated lung pathology, increased expression of RSV-A N genes, eosinophilia, enhanced IL-5, IL-13, MUC5AC, and eosinophils Major Basic Protein (MBP) production in lung tissue compared to offspring lacking matAbs. Importantly, these unexpected outcomes were not attributed to antibody-dependent enhancement (ADE) resulting from declining matAb levels over time. Notably, our findings showed a decline in secretory IgA (sIgA), mucosal IgA, and mucosal IgG levels in offspring with high matAb levels post-primary RSV challenge. We propose that this decline may be a critical factor contributing to the ineffective protection observed during secondary RSV exposure. Overall, these findings offer valuable insights into maternal vaccination against RSV, contributing to a comprehensive understanding and mitigation of potential risks associated with maternal RSV vaccination.

基金机构：National Natural Science Foundation of China [8187011078, 8217060624]; Program for Youth Innovation in Future Medicine, Chongqing Medical University [W0063]; General Program of Natural Science Foundation of Chongqing [CSTB2022NSCQ-MSX0822]; Zhuhai Innovative and Entrepreneurial Research Team Program [2120004000202]

基金资助正文：The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Natural Science Foundation of China (Grant: 8187011078, 8217060624), Program for Youth Innovation in Future Medicine, Chongqing Medical University (Number: W0063), General Program of Natural Science Foundation of Chongqing (Number: CSTB2022NSCQ-MSX0822), and Zhuhai Innovative and Entrepreneurial Research Team Program (Number: 2120004000202).