The effect of azithromycin and microbiome composition on infant rotavirus vaccine immunogenicity
Emily Deichsel, MPH, PhD
BACKGROUND: Compared to high-income countries, the effectiveness of oral rotavirus vaccine is markedly lower among children in low-income countries where childhood morbidity and mortality are the highest.
GAP: Some observational studies in low income countries found associations between microbiota composition and response to oral rotavirus vaccine. Azithromycin, a broad-spectrum macrolide antibiotic with anti-inflammatory properties, is effective against a range of intestinal pathogens, and has been shown to effectively alter the intestinal microbiota.
HYPOTHESIS: 1. Azithromycin has immunomodulatory properties and will increase the rate of RVV seroconversion, seropositivity, and GMT determined at 6 months of age. 2. Lower infant intestinal microbiota diversity (pre-RVV-1) and specific bacterial taxa (Streptococcus bovis) at baseline will be associated with an increase rate of RVV seroconversion and seropositivity at 6 months of age. 3. The association between AZ and RVV immunogenicity is mediated through changes in the intestinal microbiota diversity and composition of bacterial taxa linked to infants’ RVV immune responses.
METHODS: Infants will be randomized 1:1 to receive an oral dose of AZ or placebo during their RVV-1 and RVV-3 EPI visits, and stool and blood samples collected at their RVV-1 and at a 6-month follow-up visit will be analyzed for rotavirus vaccine immunogenicity and microbiota diversity and composition.
IMPACT: As azithromycin is incorporated into guidelines to reduce mortality in high child mortality settings, whether the effects on rotavirus vaccine immunogenicity are translated into rotavirus vaccine efficacy will be closely monitored.