BACKGROUND: Rotaviruses are the most important cause of severe acute gastroenteritis worldwide in children <5 years of age. The human, G1P 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 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 (20 [1.4%] in placebo) and P (13 [0.9%] in placebo). Vaccine efficacy against P was 59.1%
(95% CI: 32.8%; 75.3%), P was 70.9% (95% CI: 37.5%; 87.0%) and P 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™.
We thank the volunteers and their families; the members of the Clinical Trial Study Team: from Malawi, South Africa and GlaxoSmithKline, local study monitoring teams and clinical operation teams from South Africa and Malawi; the data management team; Geetha Subramanyam and Harshith Bhat, who contributed to technical writing aspects, and Lakshmi Hariharan for publication coordination and editorial assistance.
We thank personnel from PATH for contributions to study implementation
and analysis of results.