TY - JOUR
T1 - Human rotavirus vaccine Rotarix™ provides protection against diverse circulating rotavirus strains in African infants
T2 - a randomized controlled trial
AU - Steele, Andrew D.
AU - Neuzil, Kathleen M.
AU - Cunliffe, Nigel A.
AU - Madhi, Shabir A.
AU - Bos, Pieter
AU - Ngwira, Bagrey
AU - Witte, Desiree
AU - Todd, Stacy
AU - Louw, Cheryl
AU - Kirsten, Mari
AU - Aspinall, Sanet
AU - Van Doorn, Leen J.
AU - Bouckenooghe, Alain
AU - Suryakiran, Pemmaraju V.
AU - Han, Htay H.
N1 - Funding Information:
Dr. Madhi reports receiving lecture and consulting fees from GlaxoSmithKline and consulting fees from Merck; Dr. Cunliffe, receiving consulting fees and grant support from Sanofi Pasteur and GlaxoSmithKline and Suryakiran and Dr. Han are employees of GlaxoSmithKline; Dr. Han owns shares in GlaxoSmithKline. No other potential conflict of interest relevant to this article was reported.
Funding Information:
The clinical trials were funded and coordinated by GlaxoSmithKline and the PATH Rotavirus Vaccine Program, a collaboration with the WHO and the Centers for Disease Control and Prevention, with support from the Global Alliance for Vaccines and Immunization (GAVI).
PY - 2012/9/13
Y1 - 2012/9/13
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84866140456&partnerID=8YFLogxK
U2 - 10.1186/1471-2334-12-213
DO - 10.1186/1471-2334-12-213
M3 - Article
C2 - 22974466
AN - SCOPUS:84866140456
SN - 1471-2334
VL - 12
JO - BMC Infectious Diseases
JF - BMC Infectious Diseases
M1 - 213
ER -
