Department of Pediatrics, Duke University School of Medicine, Durham, NC, United States.
Program in Computational Biology and Bioinformatics, Duke University School of Medicine, Durham, NC, United States.
Front Immunol. 2023 Dec 6;14:1283343. doi: 10.3389/fimmu.2023.1283343. eCollection 2023.
It is becoming clearer that the microbiota helps drive responses to vaccines; however, little is known about the underlying mechanism. In this study, we aimed to identify microbial features that are associated with vaccine immunogenicity in infant rhesus macaques.
We analyzed 16S rRNA gene sequencing data of 215 fecal samples collected at multiple timepoints from 64 nursery-reared infant macaques that received various HIV vaccine regimens. PERMANOVA tests were performed to determine factors affecting composition of the gut microbiota throughout the first eight months of life in these monkeys. We used DESeq2 to identify differentially abundant bacterial taxa, PICRUSt2 to impute metagenomic information, and mass spectrophotometry to determine levels of fecal short-chain fatty acids and bile acids.
Composition of the early-life gut microbial communities in nursery-reared rhesus macaques from the same animal care facility was driven by age, birth year, and vaccination status. We identified a and a species that positively correlated with vaccine-elicited antibody responses, with the species exhibiting more robust findings. Analysis of -related metagenomic data revealed five metabolic pathways that significantly correlated with improved antibody responses following HIV vaccination. Given these pathways have been associated with short-chain fatty acids and bile acids, we quantified the fecal concentration of these metabolites and found several that correlated with higher levels of HIV immunogen-elicited plasma IgG.
Our findings highlight an intricate bidirectional relationship between the microbiota and vaccines, where multiple aspects of the vaccination regimen modulate the microbiota and specific microbial features facilitate vaccine responses. An improved understanding of this microbiota-vaccine interplay will help develop more effective vaccines, particularly those that are tailored for early life.
越来越明显的是，微生物群有助于驱动疫苗的反应；然而，其潜在机制知之甚少。在这项研究中，我们旨在确定与婴儿恒河猴疫苗免疫原性相关的微生物特征。
我们分析了 215 份粪便样本的 16S rRNA 基因测序数据，这些样本来自 64 只在托儿所饲养的婴儿恒河猴，它们接受了各种 HIV 疫苗方案。采用 PERMANOVA 检验来确定影响这些猴子生命最初 8 个月内肠道微生物群落组成的因素。我们使用 DESeq2 来识别差异丰富的细菌分类群，使用 PICRUSt2 来推断宏基因组信息，并用质谱法来确定粪便短链脂肪酸和胆汁酸的水平。
来自同一动物护理设施的托儿所饲养的恒河猴早期肠道微生物群落的组成受年龄、出生年份和接种疫苗状态的影响。我们确定了 和 两个与疫苗引起的抗体反应呈正相关的物种，其中 物种的相关性更强。对 - 相关宏基因组数据的分析揭示了五个与 HIV 疫苗接种后抗体反应改善显著相关的代谢途径。鉴于这些途径与短链脂肪酸和胆汁酸有关，我们对这些代谢物的粪便浓度进行了量化，发现其中几种与 HIV 免疫原诱导的血浆 IgG 水平升高相关。
我们的发现强调了微生物群和疫苗之间复杂的双向关系，疫苗方案的多个方面调节微生物群，而特定的微生物特征则促进疫苗反应。更好地理解这种微生物-疫苗相互作用将有助于开发更有效的疫苗，特别是针对生命早期的疫苗。
