A Phase 3, double-blind, randomized placebo-controlled multicenter study was undertaken in South Africa and Malawi as reported [3]. Briefly, the study included two cohorts in South Africa who were consecutively enrolled from October 2005 to

January 2006 (Cohort 1: 1828 subjects) and November 2006 to February Epigenetics inhibitor 2007 (Cohort 2: 1339 subjects). The interruption of enrollment between Cohort 1 and Cohort 2 subjects in South Africa was based on targeting completion of study-vaccine vaccination before the anticipated start of the rotavirus season in South Africa, which generally occurs between March and June [13]. Children were learn more randomly assigned individually in a 1:1:1 ratio to receive at 6, 10, and 14 weeks either a dose of placebo followed by two doses of HRV (HRV_2D); three doses of HRV (HRV_3D); or three doses of placebo.

Vaccine used in the study was the same as the commercial formulation of Rotarix and the placebo the same as vaccine-formulation without the viral antigen [14]. The study was conducted in a double-blind manner with respect to vaccine or placebo and HRV dosing schedule. The parents/guardians of the subjects, the study personnel, and the investigator were unaware of the administered treatment. Blinding was maintained for the whole study period. Study exclusion criteria included use of any investigational or non-registered product (drug or vaccine) other

than the study vaccine(s) during the study period, chronic systemic administration (defined as more than 14 days) of immunosuppressant during the study also period, administration of a vaccine not foreseen by the study protocol during the period starting from 14 days before each dose of study vaccine(s) and ending 14 days after, or administration of immunoglobulins and/or any blood products during the study period. A detailed description of testing of infants for HIV, active weekly surveillance for gastroenteritis episodes, analysis of stool samples, and safety assessment has been described [3]. Briefly, the parents or legal guardians of children were trained to complete diary cards documenting any episode of gastroenteritis and the clinical course, which were retrieved by trained surveillance officers during weekly home-visits. Stool samples were also collected from the date of first study-vaccine dose, with each episode of gastroenteritis defined as the passage of 3 or more stools that were looser than normal within a 24-h period.