@article{a3141259fadc4c12a4a67a9ea3352cde,
title = "Efficacy, immunogenicity, and safety of two doses of a tetravalent rotavirus vaccine RRV-TV in Ghana with the first dose administered during the neonatal period",
abstract = "Background. Oral rhesus/rhesus-human reassortant rotavirus tetravalent vaccine (RRV-TV) was licensed in 1998 but withdrawn in 1999 due to a rare association with intussusception, which occurred disproportionately in infants receiving their first dose at ≥90 days of age. This study examined RRV-TV for the prevention of rotavirus gastroenteritis (RV-GE) in Ghana, West Africa, with infants receiving the first dose during the neonatal period and the second before 60 days of age.Methods. In a double-blinded, randomized, placebo-controlled trial in Navrongo, Ghana, we recruited neonates to receive 2 doses of RRV-TV or placebo and followed them to age 12 months.Results. In the intention-to-treat population of 998 infants, we measured a vaccine efficacy of 63.1% against RV-GE of any severity associated with any of the 4 serotypes represented in the vaccine and 60.7% against RV-GE associated with any rotavirus serotype.Conclusions. RRV-TV in a 2-dose schedule with the first dose during the neonatal period is efficacious in preventing RV-GE in rural Ghana. Neonatal dosing results in early protection and may be the optimum schedule to avoid or significantly reduce intussusception, now reported to be associated in international settings with the 2 most widely marketed, licensed, live virus, oral rotavirus vaccines.",
keywords = "Ghana, attenuated, diarrhea, gastroenteritis, humans, infant, infantile, randomized controlled trial, rotavirus, rotavirus infections, rotavirus vaccines, vaccines",
author = "Armah, {George E.} and Kapikian, {Albert Z.} and Timo Vesikari and Nigel Cunliffe and Jacobson, {Robert M.} and Burlington, {D. Bruce} and Ruiz, {Leonard P.}",
note = "Funding Information: ed in the study, Fred N. Binka, PhD, Dean of the School of Public Health at the University of Ghana, and Akosua Ansah, MB, ChB, and Ernest C. Opoku, MD, MPH, our coinvestigators at the Navrongo Health Research Centre in Ghana. We also would like to express our appreciation for the assistance of Monica M. McNeal, MS, Division of Infectious Diseases, Children{\textquoteright}s Hospital Medical Center, Cincinnati, Ohio, who performed the serological assays for the serum antirotavirus IgA in the laboratory for Clinical Studies, and Mark A. Pallansch, PhD, Centers for Disease Control and Prevention, Atlanta, Georgia, who performed the OPV-specific neutralization antibodies. We also express our appreciation to the staff of the Electron Microscopy and Histopathology Department of the Noguchi Memorial Institute for Medical Research for the rotavirus-characterization assays. We would like to acknowledge the funding of the trial through the International Medica Foundation, a nonprofit foundation committed to the development of medical products and services and the distribution of healthcare products, services and information to families in need in neglected populations. The study was conducted in compliance with Good Clinical Practice guidelines and the research protocol was approved by the relevant institutional review boards including the Ghana Health Service Ethics Review Committee, the Noguchi Memorial Institute for Medical Research Institutional Review Board, the Navrongo Health Research Centre Institutional Review Board of the Ghana Health Service, and the Food and Drugs Board of Ghana. All human participants gave written informed consent. The trial was registered through the Pan African Clinical Trial Registry with the identification number of PACTR201110000333955. The statistical data analyses were conducted by Mark M. Crisanti, INC Research, 441 Vine Street, Cincinnati, OH 45202. Albert Z. Kapikian, MD, is supported by the intramural program of the National Institute of Allergy and Infectious Diseases. Funding Information: Potential conflicts of interest. T. V. has received advisory board fees from Merck, Sanofi Pasteur-Merck Sharp & Dohme, and Novartis, as well as served as a consultant to Pfizer and received payments for lecture service on speaker bureaus from Merck, Sanofi Pasteur-Merck Sharp & Dohme, Novartis, Pfizer, and Glaxo-Smith-Kline. N. C. received funds for serving on this study{\textquoteright}s data safety monitoring board and has served on advisory boards for Glaxo-Smith-Kline and Sanofi Pasteur-Merck Sharp & Dohme and has had a grant from Glaxo-Smith-Kline for vaccine-related research. R. M. J. has in the last 3 years served as a site principal investigator at Mayo Clinic for 2 multisite vaccine studies funded by Pfizer, Inc, as well as a member of a data monitoring committee and a safety review committee for Merck & Co., Inc, for 3 vaccine studies. L. P. R. is the President of the nonprofit International Medica Foundation that has an exclusive license to RRV-TV from the US National Institutes of Health, Public Health Service. D. B. B. is an advisory board member for AstraZeneca and was an executive at Wyeth from 1999 to 2007; he has served as a consultant to many pharmaceutical companies on development and regulation of nonro-tavirus products. L. P. R. is an employee of the International Medica Foundation, the sponsor of the clinical trial. All other authors: No reported conflicts. Funding Information: 1College of Health Sciences, University of Ghana, Legon; 2Epidemiology Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; 3Vaccine Research Center, University of Tampere, Finland; 4Department of Clinical Infection, Microbiology and Immunology, University of Liverpool, United Kingdom; 5Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota; 6Gaithersburg, Maryland, and 7International Medica Foundation, Rochester, Minnesota Funding Information: Financial support. G. E. A.{\textquoteright}s institution, the Noguchi Memorial Institute for Medical Research, University Of Ghana, received grant funds for his work as this study{\textquoteright}s principal investigator. A. Z. K. is listed as an inventor on one or more patents that relate to the tetravalent rhesus rotavirus vaccine described in the enclosed manuscript. He assigned his rights to the US Government as required by his status as an employee of the US Government. Accordingly, the US Government, and not A. Z. K. personally, controls these rights. Pursuant to the Federal Technology Transfer Act, royalties that the US Government receives through licensing of these rights are required to be distributed to the laboratory where the invention was made and to inventors. A. Z. K. understands that US Government ethics rules, to which he is subject, specifically exempt Federal Technology Transfer Act payments from conflict of interest prohibitions.",
year = "2013",
month = aug,
day = "1",
doi = "10.1093/infdis/jit174",
language = "English (US)",
volume = "208",
pages = "423--431",
journal = "Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "Oxford University Press",
number = "3",
}