PDF(Pubmed)
Abstract：
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.
摘要：
呼吸道合胞病毒（RSV）是5岁以下儿童毛细支气管炎相关住院的主要原因，再感染在一生中很常见。孕产妇接种疫苗已成为一种有希望的策略，向新生儿提供升高的抗体水平以立即保护。然而,有限的研究探索了母体抗体(matAbs)对后代继发RSV感染的保护功效.为了解决这个差距，我们采用母体RSV疫苗接种和后代继发感染的小鼠模型,评估母体抗体(matAb)水平不同的小鼠RSV再感染后的肺部病理学.此外,我们的目的是研究在二次RSV暴露后matAb水平高的后代中肺部炎症加剧的潜在原因.我们的发现表明，母体前F抗体水平升高的后代在最初的RSV感染后表现出对肺部病理的有效保护。然而,这种保护在再次感染时受到损害，表现为体重增加，加重肺部病理学，RSV-AN基因表达增加，嗜酸性粒细胞增多,增强的IL-5，IL-13，MUC5AC，与缺乏matAb的后代相比，肺组织中的嗜酸性粒细胞主要碱性蛋白（MBP）产生。重要的是,这些意外结果并非归因于matAb水平随时间下降导致的抗体依赖性增强(ADE).值得注意的是,我们的研究结果表明分泌型IgA（sIgA）下降，粘膜IgA，初发RSV攻击后matAb水平高的后代的粘膜IgG水平。我们认为，这种下降可能是导致在二次RSV暴露期间观察到的无效保护的关键因素。总的来说,这些发现为孕妇接种RSV疫苗提供了有价值的见解，有助于全面了解和减轻与孕产妇RSV疫苗接种相关的潜在风险。
