Gut microbiota composition effect the efficacy of rotavirus vaccine. Select gut microbiota impede rotavirus vaccine efficacy

The protection provided by orally-administered rotavirus (RV) vaccines is highly heterogeneous amongst 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 (FMT) 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, i.e. failure to generate RV antigens and, consequently, anti-RV antibodies following RV vaccination resulting in proneness to RV challenge after SFB levels diminished. FMT from children to mice recapitulated donor vaccination phenotype. Specifically, mice receiving FMT 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 FMT 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. In conclusion, gut microbiota composition influences RV vaccine efficacy with C. perfringens being one, perhaps of many, potential contributing taxa.

口服轮状病毒（rotavirus, RV）疫苗所提供的保护力在个体间存在显著异质性。我们提出假说：肠道微生物群组成可能会影响RV疫苗的效力。首先，我们在小鼠模型中检测了分段丝状细菌（segmented filamentous bacteria, SFB）定植对RV疫苗效力的潜在影响。随后，我们通过给小鼠移植具有较强或极弱RV疫苗应答能力的儿童粪便微生物群移植（fecal microbial transplants, FMT），探究了人类微生物组对RV疫苗接种的影响。粪便微生物群移植后，小鼠先接受RV疫苗接种，随后进行RV攻毒。SFB定植诱导出类似RV疫苗无应答的表型：即RV疫苗接种后无法产生RV抗原，进而无法生成抗RV抗体，最终在SFB水平下降后仍易受RV攻毒。将儿童的微生物群移植给小鼠可重现供体的疫苗应答表型。具体而言，接受高应答疫苗供体FMT的小鼠，在RV疫苗接种后可大量排出RV抗原，并高效产生抗RV抗体；与此同时，此类小鼠对RV攻毒具有抵抗力。与之相反，接受无RV疫苗应答儿童FMT的小鼠，其RV疫苗接种后的应答仅为轻度，且仍易受RV攻毒。微生物组分析排除了SFB的作用，但提示产气荚膜梭菌（Clostridium perfringens）可能参与其中。向悉生小鼠（gnotobiotic mice）口服接种体外培养的产气荚膜梭菌，可部分重现RV疫苗无应答者的表型。对已发表的微生物组数据进行分析发现，儿童体内产气荚膜梭菌的丰度与RV疫苗无应答呈轻度相关。综上，肠道微生物群组成会影响RV疫苗效力，而产气荚膜梭菌或许是众多潜在影响类群之一。