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

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Title: Influence of the intestinal microbiota on the immunogenicity of oral rotavirus vaccine given to infants in south India
Authors: Parker, EPK
Praharaj, I
Zekavati, A
Lazarus, RP
Giri, S
Operario, DJ
Liu, J
Iturriza-Gómara, M
Kampmann, B
John, J
Kang, G
Grassly, NC
Item Type: Journal Article
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.
Issue Date: 6-Dec-2017
Date of Acceptance: 13-Nov-2017
URI: http://hdl.handle.net/10044/1/53663
DOI: https://dx.doi.org/10.1016/j.vaccine.2017.11.031
ISSN: 0264-410X
Publisher: Elsevier
Start Page: 264
End Page: 272
Journal / Book Title: Vaccine
Volume: 36
Issue: 2
Copyright Statement: 2017 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Sponsor/Funder: Medical Research Council (MRC)
Medical Research Council (MRC)
Funder's Grant Number: MR/K010174/1B
JXR11990
Keywords: 06 Biological Sciences
07 Agricultural And Veterinary Sciences
11 Medical And Health Sciences
Virology
Publication Status: Published
Appears in Collections:Department of Medicine
Faculty of Medicine
Epidemiology, Public Health and Primary Care



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