title: 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.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Division of Gastrointestinal Sciences, Christian Medical College, Vellore, Tamil Nadu, India.
authors.forename: Kuladaipalayam Natarajan C
authors.initials: KN
authors.lastname: Sindhu
authors.affiliation: University of Liverpool, Liverpool, UK.
authors.forename: Nigel
authors.initials: N
authors.lastname: Cunliffe
authors.affiliation: Alder Hey Children's NHS Foundation Trust, Liverpool, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Peak
authors.affiliation: University of Liverpool, Liverpool, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Turner
authors.affiliation: University of Liverpool, Liverpool, UK.
authors.forename: Alistair
authors.initials: A
authors.lastname: Darby
authors.affiliation: London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Grassly
authors.affiliation: University of Liverpool, Liverpool, UK.
authors.forename: Melita
authors.initials: M
authors.lastname: Gordon
authors.affiliation: Malawi College of Medicine, Malawi.
authors.forename: Queen
authors.initials: Q
authors.lastname: Dube
authors.affiliation: Division of Gastrointestinal Sciences, Christian Medical College, Vellore, Tamil Nadu, India.
authors.forename: Sudhir
authors.initials: S
authors.lastname: Babji
authors.affiliation: Division of Gastrointestinal Sciences, Christian Medical College, Vellore, Tamil Nadu, India.
authors.forename: Ira
authors.initials: I
authors.lastname: Praharaj
authors.affiliation: Department of Child Health, Christian Medical College, Vellore, Tamil Nadu, India.
authors.forename: Valsan
authors.initials: V
authors.lastname: Verghese
authors.affiliation: University of Liverpool, Liverpool, UK.
authors.forename: Miren
authors.initials: M
authors.lastname: Iturriza-Gómara
authors.affiliation: Division of Gastrointestinal Sciences, Christian Medical College, Vellore, Tamil Nadu, India.
authors.forename: Gagandeep
authors.initials: G
authors.lastname: Kang
mesh_terms: D000349:Africa / Q000208:ethnology; D000914:Antibodies, Viral / Q000276:immunology*; D002675:Child, Preschool; D004279:DNA, Viral / Q000276:immunology; D004739:England / Q000208:ethnology; D004797:Enzyme-Linked Immunosorbent Assay; D005060:Europe / Q000208:ethnology; D005260:Female; D005759:Gastroenteritis / Q000208:ethnology / Q000276:immunology*; D000069196:Gastrointestinal Microbiome / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007194:India / Q000208:ethnology; D007223:Infant; D011446:Prospective Studies; D022243:Rotavirus Vaccines / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D004279:DNA, Viral; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D022243:Rotavirus Vaccines
keywords: Immunogenicity; Maternal antibodies; Microbiota; Polio vaccine; Rotavirus vaccine