• Occurrence of severe rotavirus (RV) gastroenteritis (GE) (score >= 11 on a 20-point Vesikari scoring system [Ruuska, 1990]) caused by the circulating wild-type RV strains in pooled HRV groups versus the placebo group. [ Time Frame: During the period from 2 weeks after the last dose of HRV vaccine or placebo until Visit 6 ] [ Designated as safety issue: No ]
  

• Occurrence of severe RV GE caused by the circulating wild-type RV strains of G1 serotype. [ Time Frame: During the period from 2 weeks after the last dose of HRV vaccine or placebo until Visit 6 ] [ Designated as safety issue: Yes ]
  
• Occurrence of severe RV GE caused by the circulating wild-type RV strains of non-G1 serotype [ Time Frame: During the period from 2 weeks after the last dose of HRV vaccine or placebo until Visit 6 ] [ Designated as safety issue: Yes ]
  
• Occurrence of any RV GE caused by the circulating wild-type RV strains [ Time Frame: During the period from 2 weeks after the last dose of HRV vaccine or placebo until Visit 6. ] [ Designated as safety issue: Yes ]
  
• Occurrence of severe RV GE caused by the circulating wild-type RV strains. [ Time Frame: During the period starting from Dose 1 of the study vaccine until Visit 6 ] [ Designated as safety issue: Yes ]
  
• In South Africa, occurrence of severe RV GE caused by the circulating wild-type RV strains for the subset of subjects who were fully vaccinated (at least 2 weeks post HRV dose 2 or 3) before the beginning of the RV season. [ Time Frame: During the period from 2 weeks after the last dose of HRV vaccine or placebo until Visit 6. ] [ Designated as safety issue: Yes ]
  
• Occurrence of severe GE. [ Time Frame: During the period from 2 weeks after the last dose of HRV vaccine or placebo until Visit 6 ] [ Designated as safety issue: Yes ]
  
• For subjects in Cohort 2 South Africa and the cohort in Malawi:Occurrence of severe RV GE caused by the circulating wild-type RV strains [ Time Frame: During the period from 2 weeks after the last dose of HRV vaccine or placebo until Visit 7, and from Visit 6 to Visit 7. ] [ Designated as safety issue: Yes ]
  
• For subjects in Cohort 2 South Africa and the cohort in Malawi: Occurrence of hospitalisation and/or supervised re-hydration therapy in a medical facility for RV GE caused by the circulating wild-type RV strains [ Time Frame: During the period from 2 weeks after the last dose of HRV vaccine or placebo until Visit 7, and from Visit 6 to Visit 7. ] [ Designated as safety issue: Yes ]
  
• For subjects in Cohort 2 South Africa and the cohort in Malawi: Occurrence of severe RV GE caused by the circulating wild-type RV strains of G1 serotype [ Time Frame: During the period from 2 weeks after the last dose of HRV vaccine or placebo until Visit 7, and from Visit 6 to Visit 7. ] [ Designated as safety issue: Yes ]
  
• For subjects in Cohort 2 South Africa and the cohort in Malawi: Occurrence of severe RV GE caused by the circulating wild-type RV strains of non-G1 serotype [ Time Frame: During the period from 2 weeks after the last dose of HRV vaccine or placebo until Visit 7, and from Visit 6 to Visit 7 ] [ Designated as safety issue: Yes ]
  
• For all subjects, occurrence of adverse events (AEs)/serious adverse events (SAEs) leading to drop-out [ Time Frame: Throughout the entire study period. ] [ Designated as safety issue: Yes ]
  
• For all subjects, occurrence of SAEs. [ Time Frame: Throughout the entire study period ] [ Designated as safety issue: Yes ]
  
• In a subset of subjects, seroconversion rate and Geometric Mean concentration (GMC) to anti-rotavirus immunoglobulin A (IgA) antibody. [ Time Frame: At Visit 4 ] [ Designated as safety issue: No ]
  
• In all subjects, seropositivity rate and GMC to anti-rotavirus IgA antibody [ Time Frame: At Visit 4 ] [ Designated as safety issue: No ]
  
• Occurrence of hospitalisation and/or supervised re-hydration therapy (equivalent to WHO plan B or C) in a medical facility for RV GE caused by the circulating wild-type RV strains [ Time Frame: During the period from 2 weeks after the last dose of human rotavirus vaccine (HRV) vaccine or placebo until Visit 6. ] [ Designated as safety issue: Yes ]
  

The study will have three groups: Group HRV 3-Dose, Group HRV 2-Dose and Group Placebo. Three-dose immunisation will be administered in healthy infants at approximately 6, 10, and 14 weeks of age. Routine EPI vaccinations will be administered concomitantly with the study vaccines. This study will also evaluate immunogenicity and safety relative to the placebo.

Inclusion criteria:

• Subjects who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol should be enrolled in the study.
• A male or female child between, and including, 5 and 10 weeks of age at the time of the first study vaccination.
• Written informed consent obtained from the parent or guardian of the subject who is of legal age
• Healthy subjects as established by medical history and clinical examination before entering into the study.
• In South Africa, birth weight > 2000 g or if weight unknown, gestation period > 36 weeks.

Exclusion criteria:

• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period.
• Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product
• Planned administration of a vaccine not foreseen by the study protocol within 14 days before each dose of study vaccine(s) and ending 14 days after.
• Chronic administration (defined as more than 14 days) of immunosuppressants since birth.
• History of use of experimental rotavirus vaccine.
• Previous routine vaccination except BCG, HBV and OPV vaccination at birth
• Any clinically significant history of chronic gastrointestinal disease including any uncorrected congenital malformation of the gastrointestinal tract, intussusception or other medical condition determined to be serious by the investigator.
• Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination
• History of allergic disease or reaction likely to be exacerbated by any component of the vaccine.
• Acute disease at the time of enrolment.
• Gastroenteritis within 7 days preceding the first study vaccine administration
• Previous confirmed occurrence of RV GE.
• A family history of congenital or hereditary immunodeficiency.
• Administration of immunoglobulins and/or blood products since birth or planned administration during the study period.
• History of any neurologic disorders or seizures.
• Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests.