title: Human rotavirus vaccine Rotarix™ provides protection against diverse circulating rotavirus strains in African infants: a randomized controlled trial.
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™.
  
  
  BACKGROUND
  NCT00241644.
authors.affiliation: Rotavirus Vaccine Program, PATH, 2201 Westlake Ave, Seattle, WA 98121, USA. duncan.steele@gatesfoundation.org
authors.forename: Andrew Duncan
authors.initials: AD
authors.lastname: Steele
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Neuzil
authors.forename: Nigel A
authors.initials: NA
authors.lastname: Cunliffe
authors.forename: Shabir A
authors.initials: SA
authors.lastname: Madhi
authors.forename: Pieter
authors.initials: P
authors.lastname: Bos
authors.forename: Bagrey
authors.initials: B
authors.lastname: Ngwira
authors.forename: Desiree
authors.initials: D
authors.lastname: Witte
authors.forename: Stacy
authors.initials: S
authors.lastname: Todd
authors.forename: Cheryl
authors.initials: C
authors.lastname: Louw
authors.forename: Mari
authors.initials: M
authors.lastname: Kirsten
authors.forename: Sanet
authors.initials: S
authors.lastname: Aspinall
authors.forename: Leen Jan
authors.initials: LJ
authors.lastname: Van Doorn
authors.forename: Alain
authors.initials: A
authors.lastname: Bouckenooghe
authors.forename: Pemmaraju V
authors.initials: PV
authors.lastname: Suryakiran
authors.forename: Htay Htay
authors.initials: HH
authors.lastname: Han
mesh_terms: D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005759:Gastroenteritis / Q000453:epidemiology* / Q000517:prevention & control*; D005838:Genotype; D006801:Humans; D007223:Infant; D008295:Malawi / Q000453:epidemiology; D008297:Male; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012401:Rotavirus / Q000302:isolation & purification; D012400:Rotavirus Infections / Q000453:epidemiology* / Q000517:prevention & control*; D022243:Rotavirus Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D013019:South Africa / Q000453:epidemiology; D014611:Vaccination / Q000379:methods*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology
chemical_list: C492457:RIX4414 vaccine; D022243:Rotavirus Vaccines; D014613:Vaccines, Attenuated