Influence of the intestinal microbiota on the immunogenicity of oral rotavirus vaccine given to infants in south India

Edward P.K Parker,Ira Praharaj,Anna Zekavati,Robin P Lazarus,Sidhartha Giri,Darwin J Operario,Jie Liu,Eric Houpt,Miren Iturriza-Gómara,Beate Kampmann,Jacob John,Gagandeep Kang,Nicholas C Grassly

doi:10.1016/j.vaccine.2017.11.031

Abstract

Oral rotavirus vaccines have consistently proven to be less immunogenic among infants in developing countries. Discrepancies in the intestinal microbiota, including a greater burden of enteropathogens and an altered commensal community composition, may contribute to this trend by inhibiting the replication of vaccine viruses. To test this possibility, we performed a nested case–control study in Vellore, India, in which we compared the intestinal microbiota of infants who responded serologically or not after two doses of Rotarix delivered at 6 and 10 weeks of age as part of a clinical trial (CTRI/2012/05/002677). The prevalence of 40 bacterial, viral, and eukaryotic pathogen targets was assessed in pre-vaccination stool samples from 325 infants using singleplex real-time PCR on a Taqman array card (TAC). In a subset of 170 infants, we assessed bacterial microbiota composition by sequencing the 16S rRNA gene V4 region. Contrary to expectations, responders were more likely than non-responders to harbor ≥1 bacterial enteropathogen at dose 1 (26% [40/156] vs 13% [21/157] of infants with TAC results who completed the study per protocol; χ2, P = .006), although this was not apparent at dose 2 (24% [38/158] vs 23% [36/158]; P = .790). Rotavirus shedding after dose 1 was negatively correlated with the replication of co-administered oral poliovirus vaccine (OPV). We observed no consistent differences in composition or diversity of the 16S bacterial microbiota according to serological response, although rotavirus shedding was associated with slightly more bacterial taxa pre-vaccination. Overall, our findings demonstrate an inhibitory effect of co-administered OPV on the first dose of Rotarix, consistent with previous studies, but in the context of OPV co-administration we did not find a strong association between other components of the intestinal microbiota at the time of vaccination and Rotarix immunogenicity.

Highlights

Each year, an estimated 215,000 children die of severe gastroenteritis associated with rotavirus infection, including between 47,000 and 79,000 in India [1,2]
10 weeks, we observed a significant increase in the odds of seroconversion when !1 pathogen was present at both doses – an effect that was absent among individuals infected at only one dose
This observation is consistent with an inhibitory effect of oral poliovirus vaccine (OPV) on RV1 [37]

Summary

Introduction

An estimated 215,000 children die of severe gastroenteritis associated with rotavirus infection, including between 47,000 and 79,000 in India [1,2]. Two internationallylicensed oral rotavirus vaccines, Rotarix (RV1) and RotaTeq, are currently available, their efficacy is impaired in low-income coun-. Mechanisms responsible for this phenomenon remain uncertain, but may include maternal antibodies, histo blood group antigen phenotype, malnutrition, environmental enteropathy, and interference by enteric infections [4,5,6,7]. In a systematic review of oral poliovirus vaccine (OPV) trials, we observed a reduction in the odds of seroconversion and vaccine virus shedding among individuals infected with non-polio enteroviruses (NPEVs) [8].

Methods

Results

Conclusion