Gut microbiota modulate immune responses to orally and parenterally administered rotavirus in mice

Zhenda Shi1,2,3, Sung-Sil Moon4, Jun Zou5

  • 1Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA. pst2@cdc.gov.

NPJ Vaccines
|April 20, 2025
PubMed

Insights

Gut microbes impact rotavirus (RV) vaccine effectiveness. Specific bacteria can block oral RV immunity, while altering microbiota enhances intramuscular RV vaccine responses in mice.

Area of Science:

  • Microbiology
  • Immunology
  • Vaccinology

Background:

  • Rotavirus (RV) is a major cause of severe diarrhea in infants, leading to significant morbidity and mortality worldwide.
  • Current oral RV vaccines have variable efficacy, highlighting the need for improved vaccination strategies.
  • The influence of the gut microbiome on immune responses to RV vaccination remains incompletely understood.

Purpose of the Study:

  • To investigate the role of gut microbiota in modulating immune responses to oral and intramuscular rotavirus (RV) vaccination.
  • To identify specific microbial factors and host immune pathways involved in RV vaccine efficacy.

Main Methods:

  • Murine models were used to assess the impact of gut microbiota on oral and intramuscular RV immunization.
  • Microbiota composition was analyzed, and specific bacterial components were tested for their effects on RV immunity.
  • Host immune responses, including antibody generation and chemokine expression (Reg3β, Reg3γ, RANTES, Eotaxin), were measured.
  • The efficacy of intramuscular RV vaccination was evaluated following antibiotic-induced microbiota depletion.

Main Results:

  • Certain gut bacteria, such as segmented filamentous bacteria, were found to reduce oral RV infection and antibody responses.
  • This microbiota-mediated blockade was linked to increased intestinal Reg3β and Reg3γ expression.
  • Intramuscular (IM) RV administration after oral inoculations enhanced antibody production and protection against RV challenge.
  • Antibiotic-induced depletion of gut microbiota improved the efficacy of IM RV vaccination in poorly responding animals, associated with elevated serum RANTES and Eotaxin.

Conclusions:

  • Gut microbiota composition significantly influences the immunogenicity and efficacy of both oral and intramuscular rotavirus (RV) vaccines.
  • Targeting or manipulating the gut microbiome, or utilizing IM vaccination strategies, may enhance RV vaccine effectiveness.
  • Understanding these host-microbe-vaccine interactions is crucial for developing more robust RV vaccination approaches.

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