Administration of rotavirus vaccine was staggered around the second and third EPI visits at 10 and 14 weeks of age; thus Rotarix™ was given with OPV at 10 and 14 weeks of age or 2 weeks after OPV at 12 and 16 weeks of age. An assessment of antibody response and seroconversion pre-vaccination and 1 month after dose 2 was made. In addition,

rotavirus antigen excretion was measured on a subset of subjects on days 1, 4, and 7 after each dose of vaccine BKM120 clinical trial or placebo, with the hypothesis that stool shedding of rotavirus antigen would reflect vigorous replication of the vaccine virus and thus a measure of “vaccine take. Stool shedding of rotavirus antigen after dose 1 was lower on day 4 (6% versus 10%) and day 7 (6% versus 14%) after Rotarix™ vaccination with OPV versus without OPV, respectively. For time points combined (0, 4, or 7 days) after either dose, shedding of rotavirus antigen was 43% lower in the OPV group (18%) compared with the IPV group Anti-diabetic Compound Library (31%), indicating interference of rotavirus vaccine take in the presence of OPV. Although IgA GMC and seroconversion were not assessed after dose 1, GMCs were 38% (47 U/ml versus 75 U/ml, respectively) and seroconversion was 15% (57% versus 67% respectively) lower after dose 2 when the Rotarix™ series was given with OPV compared to without OPV. Latin America [2],

[29] and [35]: No studies have directly examined the effect of OPV on Rotarix™ in a randomized controlled design in Latin America. However, two separate Phase III efficacy and immunogenicity trials have

been conducted in Latin America – one where Rotarix™ was administered without OPV [2] and [35] and another where Rotarix™ was co-administered with OPV [29]. Rotarix™ was given separated by a 2-week interval with OPV (either before or after) in a large trial from 11 Latin American Libraries countries (Colombia, Dominican Republic, Honduras, Peru, Argentina, Brazil, ADP ribosylation factor Mexico, Argentina, Nicaragua, Panama, Chile, and Venezuela) [2] and [35]. In six of these 11 countries (Colombia, Dominican Republic, Honduras, Peru, Argentina, Brazil), efficacy and immunogenicity were also assessed in a later trial in which Rotarix™ was co-administered with OPV [29] and [35]. We computed the mean antirotavirus antibody GMC for the six countries that were part of the 11-country study where Rotarix™ was given without OPV [35] and compared it with the antirotavirus antibody GMC in the same six countries when Rotarix™ was given with OPV [29]. In both these studies, dose 1 was given at 6–12 weeks of age and dose 2 at 12–16 weeks of age. When the 2-dose Rotarix™ series was given concurrently with OPV compared to without OPV antirotavirus antibody GMC were 32% lower (66 U/ml [95% CI = 50–87] versus 96 U/ml [95% CI = 57–163]) and seroconversion rates were 18% lower (61% [95% CI = 54–69] versus 75% [95% CI = 59–87]) in the presence of OPV. Of note, despite the difference in immunogenicity, a similar efficacy (∼82–85%) was observed in both studies.