Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia.
Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia; Cherokee Nation Operational Solutions, Cherokee Federal, Atlanta, Georgia and Tulsa, Oklahoma; Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia.
Cell Mol Gastroenterol Hepatol. 2024;18(5):101393. doi: 10.1016/j.jcmgh.2024.101393. Epub 2024 Aug 22.
BACKGROUND & AIMS: The protection provided by rotavirus (RV) vaccines is highly heterogeneous among individuals. We hypothesized that microbiota composition might influence RV vaccine efficacy.
First, we examined the potential of segmented filamentous bacteria (SFB) colonization to influence RV vaccine efficacy in mice. Next, we probed the influence of human microbiomes on RV vaccination via administering mice fecal microbial transplants (FMTs) from children with robust or minimal RV vaccine responsiveness. Post-FMT, mice were subjected to RV vaccination followed by RV challenge.
SFB colonization induced a phenotype that was reminiscent of RV vaccine failure (ie, failure to generate RV antigens and, consequently, anti-RV antibodies following RV vaccination resulting in proneness to RV challenge after SFB levels diminished). FMTs from children to mice recapitulated donor vaccination phenotype. Specifically, mice receiving FMTs from high-responsive vaccinees copiously shed RV antigens and robustly generated anti-RV antibodies following RV vaccination. Concomitantly, such mice were impervious to RV challenge. In contrast, mice receiving FMTs from children who had not responded to RV vaccination exhibited only modest responses to RV vaccination and, concomitantly, remained prone to RV challenge. Microbiome analysis ruled out a role for SFB but suggested involvement of Clostridium perfringens. Oral administration of cultured C. perfringens to gnotobiotic mice partially recapitulated the RV vaccine non-responder phenotype. Analysis of published microbiome data found C. perfringens abundance in children modestly associated with RV vaccine failure.
Microbiota composition influences RV vaccine efficacy with C. perfringens being one, perhaps of many, potential contributing taxa.
轮状病毒（RV）疫苗的保护作用在个体之间存在很大差异。我们假设微生物群落组成可能会影响 RV 疫苗的效果。
首先，我们研究了分段丝状菌（SFB）定植的可能性，以影响小鼠的 RV 疫苗效果。接下来，我们通过给予对 RV 疫苗反应强烈或反应较弱的儿童的粪便微生物移植（FMT），探究人类微生物组对 RV 疫苗接种的影响。FMT 后，对小鼠进行 RV 疫苗接种和 RV 攻毒。
SFB 定植诱导出一种类似于 RV 疫苗失败的表型（即 RV 疫苗接种后未能产生 RV 抗原，因此未能产生抗 RV 抗体，导致 SFB 水平降低后 RV 攻毒易感性增加）。来自儿童的 FMT 使小鼠再现了供体疫苗接种表型。具体来说，接受高反应性疫苗接种者 FMT 的小鼠大量排出 RV 抗原，并在 RV 疫苗接种后产生强烈的抗 RV 抗体。同时，这些小鼠对 RV 攻毒具有免疫力。相比之下，接受未对 RV 疫苗接种有反应的儿童 FMT 的小鼠对 RV 疫苗接种仅有适度反应，同时仍然容易受到 RV 攻毒的影响。微生物组分析排除了 SFB 的作用，但提示产气荚膜梭菌的参与。对无菌小鼠口服培养的产气荚膜梭菌部分再现了 RV 疫苗非应答者表型。对已发表的微生物组数据的分析发现，儿童中产气荚膜梭菌的丰度与 RV 疫苗失败有一定的相关性。
微生物群落组成影响 RV 疫苗的效果，产气荚膜梭菌可能是众多潜在相关分类群之一。
