Early-life antibiotic-driven dysbiosis leads to dysregulated vaccine immune responses in mice.

Miriam Lynn, Tumes Damon, Jocelyn Choo, Anastasia Sribnaia, Stephen Blake, Lex Leong, Graeme Young, Helen Marshall, Steven Wesselingh, Geraint Rogers, David Lynn

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

Abstract

Antibody-mediated responses play a critical role in vaccine-mediated immunity. However, for reasons that are poorly understood, these responses are highly variable between individuals. Using a mouse model, we report that antibiotic-driven intestinal dysbiosis, specifically in early life, leads to significantly impaired antibody responses to five different adjuvanted and live vaccines. Restoration of the commensal microbiota following antibiotic exposure rescues these impaired responses. In contrast, antibiotic-treated adult mice do not exhibit impaired antibody responses to vaccination. Interestingly, in contrast to impaired antibody responses, immunized mice exposed to early-life antibiotics display significantly enhanced T cell cytokine recall responses upon ex vivo restimulation with the vaccine antigen. Our results demonstrate that, in mice, antibiotic-driven dysregulation of the gut microbiota in early life can modulate immune responses to vaccines that are routinely administered to infants worldwide. Using an infant mouse model, Lynn, Tumes, and colleagues report that antibiotic-driven dysbiosis in early life leads to impaired antibody responses to five vaccines that are administered to human infants worldwide. In contrast, ex vivo cytokine recall responses are elevated. Restoring the commensal microbiota is sufficient to rescue impaired antibody responses.

Original languageEnglish
Pages (from-to)653-660.e1-e5
Number of pages14
JournalCell Host and Microbe
Volume23
Issue number5
DOIs
Publication statusPublished - 9 May 2018

Keywords

  • CD4+ T cells
  • antibody response
  • early-life
  • antibiotics
  • vaccines
  • microbiota
  • CD4 T cells

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