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Open Access Highly Accessed Research article

Human rotavirus vaccine Rotarix™ provides protection against diverse circulating rotavirus strains in African infants: a randomized controlled trial

Andrew Duncan Steele12*, Kathleen M Neuzil1, Nigel A Cunliffe3, Shabir A Madhi45, Pieter Bos6, Bagrey Ngwira7, Desiree Witte37, Stacy Todd3, Cheryl Louw8, Mari Kirsten9, Sanet Aspinall10, Leen Jan Van Doorn11, Alain Bouckenooghe1213, Pemmaraju V Suryakiran13 and Htay Htay Han13

Author Affiliations

1 Rotavirus Vaccine Program, PATH, 2201 Westlake Ave, Seattle, WA, 98121, USA

2 Initiative for Vaccine Research, WHO, 22 Appia Ave, Geneva, 1211, Switzerland

3 Department of Clinical Infection, Microbiology & Immunology, Institute of Infection and Global Health, University of Liverpool, Liverpool, England

4 National Institute for Communicable Diseases: a division of National Health Laboratory Services, Sandringham, South Africa

5 Department of Science and Technology National Research Foundation: Vaccine Preventable Diseases, University of the Witwatersrand, Johannesburg, South Africa

6 MRC Diarrhoeal Pathogens Research Unit, University of Limpopo, Limpopo, South Africa

7 Department of Community Health, College of Medicine, Blantyre, Malawi

8 Madibeng Centre for Research, Brits, South Africa

9 Department of Paediatric Surgery, University of Pretoria, Pretoria, RSA

10 Synexus Clinical Research SA/Rota Consortium, Pretoria, South Africa

11 DDL Diagnostic Laboratory, Voorburg, The Netherlands

12 Sanofi Pasteur, Singapore, Singapore

13 GSK Biologicals, Rixensart, Belgium

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BMC Infectious Diseases 2012, 12:213  doi:10.1186/1471-2334-12-213

Published: 13 September 2012

Abstract

Background

Rotaviruses are the most important cause of severe acute gastroenteritis worldwide in children <5 years of age. The human, G1P[8] rotavirus vaccine Rotarix™ significantly reduced severe rotavirus gastroenteritis episodes in a Phase III clinical trial conducted in infants in South Africa and Malawi. This paper examines rotavirus vaccine efficacy in preventing severe rotavirus gastroenteritis, during infancy, caused by the various G and P rotavirus types encountered during the first rotavirus-season.

Methods

Healthy infants aged 5–10 weeks were enrolled and randomized into three groups to receive either two (10 and 14 weeks) or three doses of Rotarix™ (together forming the pooled Rotarix™ group) or three doses of placebo at a 6,10,14-week schedule. Weekly home visits were conducted to identify gastroenteritis episodes. Rotaviruses were detected by ELISA and genotyped by RT-PCR and nucleotide sequencing. The percentage of infants with severe rotavirus gastroenteritis caused by the circulating G and P types from 2 weeks post-last dose until one year of age and the corresponding vaccine efficacy was calculated with 95% CI.

Results

Overall, 4939 infants were vaccinated and 4417 (pooled Rotarix™ = 2974; placebo = 1443) were included in the per protocol efficacy cohort. G1 wild-type was detected in 23 (1.6%) severe rotavirus gastroenteritis episodes from the placebo group. This was followed in order of detection by G12 (15 [1%] in placebo) and G8 types (15 [1%] in placebo). Vaccine efficacy against G1 wild-type, G12 and G8 types were 64.1% (95% CI: 29.9%; 82%), 51.5% (95% CI:-6.5%; 77.9%) and 64.4% (95% CI: 17.1%; 85.2%), respectively. Genotype P[8] was the predominant circulating P type and was detected in 38 (2.6%) severe rotavirus gastroenteritis cases in placebo group. The remaining circulating P types comprised of P[4] (20 [1.4%] in placebo) and P[6] (13 [0.9%] in placebo). Vaccine efficacy against P[8] was 59.1% (95% CI: 32.8%; 75.3%), P[4] was 70.9% (95% CI: 37.5%; 87.0%) and P[6] was 55.2% (95% CI: -6.5%; 81.3%)

Conclusions

Rotarix™ vaccine demonstrated efficacy against severe gastroenteritis caused by diverse circulating rotavirus types. These data add to a growing body of evidence supporting heterotypic protection provided by Rotarix™.

Trial registration number

NCT00241644