ena-STUDY-WASHINGTON UNIVERSITY  SCHOOL OF MEDICINE-19-03-2018-16:01:03:460-2120
Effect of antibiotic microbiome modulation on rotavirus vaccine immunogenicity: a human, randomized-control proof-of-concept trial
Rotavirus (RV) causes serious childhood gastroenteritis. Rotavirus vaccines (RVV) have lower effectiveness in low-income countries. The intestinal microbiome correlates with RVV immunogenicity.  This proof-of-concept, randomized-controlled, open-label trial tested if microbiome modulation improves RVV immunogenicity.  Adults were randomized: 7-days broad-spectrum (oral vancomycin, ciprofloxacin, metronidazole), narrow-spectrum (vancomycin), or no antibiotics, then vaccinated with RVV, 21/group per-protocol.  Baseline anti-RV IgAs were high. There were no 7,14, (secondary) or 28-day (primary) anti-RV IgA titer differences, but 7-day boosting (>2-fold change, exploratory) was higher in narrow-spectrum subjects (8/21 vs. 1/21 each, p=0·021).  More subjects in narrow and broad-spectrum groups shed RV (8/21 each vs. 1/21, p=0·02) and narrow-spectrum had higher OD-shedding overall vs. control (p=0·0027). Both antibiotic treatments decreased Bacteroidetes; only vancomycin expanded Proteobacteria and diminished Firmicutes abundance. Despite the negative primary endpoint, this study demonstrates microbiota modification alters RVV response and supports further exploration of microbiome manipulation to improve RVV immunogenicity in low-income countries.
Rotavirus (RV) causes serious childhood gastroenteritis. Rotavirus vaccines (RVV) have lower effectiveness in low-income countries. The intestinal microbiome correlates with RVV immunogenicity.  This proof-of-concept, randomized-controlled, open-label trial tested if microbiome modulation improves RVV immunogenicity.  Adults were randomized: 7-days broad-spectrum (oral vancomycin, ciprofloxacin, metronidazole), narrow-spectrum (vancomycin), or no antibiotics, then vaccinated with RVV, 21/group per-protocol.  Baseline anti-RV IgAs were high. There were no 7,14, (secondary) or 28-day (primary) anti-RV IgA titer differences, but 7-day boosting (>2-fold change, exploratory) was higher in narrow-spectrum subjects (8/21 vs. 1/21 each, p=0·021).  More subjects in narrow and broad-spectrum groups shed RV (8/21 each vs. 1/21, p=0·02) and narrow-spectrum had higher OD-shedding overall vs. control (p=0·0027). Both antibiotic treatments decreased Bacteroidetes; only vancomycin expanded Proteobacteria and diminished Firmicutes abundance. Despite the negative primary endpoint, this study demonstrates microbiota modification alters RVV response and supports further exploration of microbiome manipulation to improve RVV immunogenicity in low-income countries.