Sutterella and its metabolic pathways positively correlate with vaccine-elicited antibody responses in infant rhesus macaques

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  • Jiang D.
    • Other Affiliation: Duke University School of Medicine
  • Goswami R.
    • Other Affiliation: Weill Cornell Medicine
  • Dennis M.
    • Other Affiliation: Weill Cornell Medicine
  • Heimsath H.
    • Other Affiliation: Duke University School of Medicine
  • Kozlowski P.A.
    • Other Affiliation: Louisiana State University Health Sciences Center
  • Ardeshir A.
    • Other Affiliation: University of California, Davis
  • Van Rompay K.K.A.
    • Other Affiliation: University of California, Davis
  • De Paris K.
    • Affiliation: School of Medicine, Department of Microbiology and Immunology
  • Permar S.R.
    • Other Affiliation: Weill Cornell Medicine
  • Surana N.K.
    • Other Affiliation: Duke University School of Medicine
Abstract
  • Introduction: 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. Methods: 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. Results: 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 Sutterella and a Rodentibacter species that positively correlated with vaccine-elicited antibody responses, with the Sutterella species exhibiting more robust findings. Analysis of Sutterella-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. Discussion: 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.
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  • Article
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  • In Copyright
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  • Attribution 4.0 International
Journal title
  • Frontiers in Immunology
Journal volume
  • 14
Language
  • English
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  • Publisher
Funder
  • Center for AIDS Research, University of Washington, CFAR, (P30 AI064518, R25 AI140495)
  • National Institutes of Health, NIH, (P01 AI117915, P01 AI178377)
  • Center for AIDS Research, Emory University, CFAR
ISSN
  • 1664-3224
Publisher
  • Frontiers Media SA

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