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  • Impact of maternal antibodies and infant gut microbiota on the immunogenicity of rotavirus vaccines in African, Indian and European infants: protocol for a prospective cohort study

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Public health
Protocol
Impact of maternal antibodies and infant gut microbiota on the immunogenicity of rotavirus vaccines in African, Indian and European infants: protocol for a prospective cohort study
  1. Kuladaipalayam Natarajan C Sindhu1,
  2. Nigel Cunliffe2,
  3. Matthew Peak3,
  4. Mark Turner2,
  5. Alistair Darby2,
  6. Nicholas Grassly4,
  7. Melita Gordon2,
  8. Queen Dube5,
  9. Sudhir Babji1,
  10. Ira Praharaj1,
  11. Valsan Verghese6,
  12. Miren Iturriza-Gómara2,
  13. Gagandeep Kang1
  1. 1Division of Gastrointestinal Sciences, Christian Medical College, Vellore, Tamil Nadu, India
  2. 2University of Liverpool, Liverpool, UK
  3. 3Alder Hey Children's NHS Foundation Trust, Liverpool, UK
  4. 4London School of Hygiene and Tropical Medicine, London, UK
  5. 5Malawi College of Medicine, Malawi
  6. 6Department of Child Health, Christian Medical College, Vellore, Tamil Nadu, India
  1. Correspondence to Professor Gagandeep Kang; gkang{at}cmcvellore.ac.in

Abstract

Introduction Gastroenteritis is the leading cause of morbidity and mortality among young children living in resource-poor settings, majority of which is attributed to rotavirus. Rotavirus vaccination can therefore have a significant impact on infant mortality. However, rotavirus vaccine efficacy in Sub-Saharan Africa and Southeast Asia is significantly lower than in high-income countries. Maternally derived antibodies, infant gut microbiota and concomitant oral polio vaccination have been proposed as potential reasons for poor vaccine performance in low-income settings. The overall aim of this study is to compare the role of maternally derived antibodies and infant gut microbiota in determining immune response to rotavirus vaccine in high-income and low-income settings, using the same vaccine and a similar study protocol.

Methods and analysis The study is an observational cohort in three countries—Malawi, India and UK. Mothers will be enrolled in third trimester of pregnancy and followed up, along with infants after delivery, until the infant completes two doses of oral rotavirus vaccine (along with routine immunisation). The levels of prevaccination maternally derived rotavirus-specific antibodies (IgG) will be correlated with infant seroconversion and antibody titres, 4 weeks after the second dose of rotavirus vaccine. Both within-country and between-country comparisons of gut microbiome will be carried out between children who seroconvert and those who do not. The impact of oral polio vaccine coadministration on rotavirus vaccine response will be studied in Indian infants.

Ethics and dissemination Ethical approvals have been obtained from Integrated Research Application System (IRAS, NHS ethics) in UK, College of Medicine Research and Ethics Committee (COMREC) in Malawi and Institutional Review Board (IRB), Christian Medical College, Vellore in India. Participant recruitment and follow-up is ongoing at all three sites. Analysis of data, followed by publication of the results, is expected in 2018.

  • Rotavirus vaccine
  • Immunogenicity
  • Microbiota
  • Maternal antibodies
  • Polio vaccine

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/

https://doi.org/10.1136/bmjopen-2017-016577

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    Footnotes

    • MI-G and GK are joint senior authors.

    • Contributors GK, MI-G, NC, MP, MT, MG and QD conceived the study, drafted the original protocol and provided critical revision of the final draft. NG provided statistical expertise. NC, QD, KNCS and VV supplied information about recruitment, consenting, clinical management, data handling, finances, record keeping, participant withdrawal and reporting. AD, IP and SB provided information and standard operating procedures on microbiota methods and immunoassays. All authors were involved in the revision of the protocol manuscript, have agreed to the final content and will be accountable for accuracy and integrity of the work.

    • Funding The UK and Malawi sites of the study are funded through Medical Research Council/Department for International Development (MRC/DFID), while the site in India is funded through DBT (Department of Biotechnology), India.

    • Competing interests None declared.

    • Patient consent Obtained.

    • Ethics approval Ethics approvals have been obtained from Integrated Research Application System (IRAS, NHS ethics) in UK, College of Medicine Research and Ethics Committee (COMREC) in Malawi and Institutional Review Board (IRB), Christian Medical College, Vellore in India.

    • Provenance and peer review Not commissioned; peer reviewed for ethical and funding approval prior to submission.