Rotavirus Vaccine Response Correlates with the Infant Gut Microbiota Composition in Pakistan

Vanessa Harris, Asad Ali, Susana Fuentes, Katri Korpela, Momin Kazi, Jacqueline Tate, Umesh Parashar, W. Joost Wiersinga, Carlo Giaquinto, Carolina de Weerth, Willem M. de Vos

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Abstract

Background Rotavirus (RV) is the leading cause of diarrhea-related death in children worldwide, and ninety-five percent of rotavirus deaths occur in Africa and Asia. Rotavirus vaccines (RVV) can dramatically reduce RV deaths, but have low efficacy in low-income settings where they are most needed. The intestinal microbiome may contribute to this decreased RVV efficacy. This pilot study hypothesizes that infants' intestinal microbiota composition correlates with RVV immune responses and that RVV responders have different gut microbiota as compared to non-responders. Methods We conducted a nested, matched case-control study comparing the pre-vaccination intestinal microbiota composition between 10 6-week old Pakistani RVV-responders, 10 6-week old Pakistani RVV non-responders, and 10 healthy Dutch infants. RVV response was defined as an Immunoglobulin A of ≥20 IU/mL following Rotarix™(RV1) vaccination in an infant with a pre-vaccination IgA <20. Infants were matched in a 1:1 ratio using ranked variables: RV1 dosing schedule (6/10/14; 6/10; or 10/14 weeks), RV season, delivery mode, delivery place, breastfeeding practices, age and gender. Fecal microbiota analysis was performed using a highly reproducible phylogenetic microarray. Results RV1 response correlated with a higher relative abundance of bacteria belonging to Clostridium cluster XI and Proteobacteria, including bacteria related to Serratia and Escherichia coli. Remarkably, abundance of these Proteobacteria was also significantly higher in Dutch infants when compared to RV1-non-responders in Pakistan. Conclusions This small but carefully matched study showed the intestinal microbiota composition to correlate with RV1 seroconversion in Pakistan infants, identifying signatures shared with healthy Dutch infants. Clinicaltrials.gov: NCT02220439
Original languageEnglish
Pages (from-to)93-101
JournalGut Microbes
Volume9
Issue number2
Early online date2017
DOIs
Publication statusPublished - 2018

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