While the

differences in antibody response observed may not be clinically relevant in populations with robust immune responses, in these African populations with much lower immune responses, any further decrease in anti-rotavirus serum IgA and SNA responses may have important implications in regard to protection. Additional investigations are required to further dissect the immunogenicity data obtained from the group of African subjects who did not receive OPV and PRV concomitantly to better understand the lower immune responses in African children, as compared to those in subjects in the US, EU, Taiwan, MK-2206 concentration Korea and Latin America. The participants in this study who did not receive OPV concomitantly (on the same day) may have actually received OPV one or two days before or after administration of PRV. Administration of OPV one or two days before

the administration of the rotavirus vaccine can potentially interfere more with the replication of the rotavirus vaccine than when OPV and the rotavirus vaccine are given on the same day. In addition, it is important to highlight that this study was not designed to evaluate the immunogenicity of PRV when administered concomitantly or separately with OPV; therefore, these comparisons are purely observational. The observation that between pD1 (4–10 weeks of age) and PD3, approximately 20% of the participants Regorafenib concentration who received a placebo had a sero-response specific for rotavirus suggests that the rate of exposure to naturally occurring rotavirus crotamiton is high in these African countries and that by 5 months of age many of these children could

have been naturally immunized. These data highlight the high burden of rotavirus disease in African countries. However, enrollment patterns and rotavirus circulation patterns influence the interpretation of these background exposure rates. Among the 3 African countries, Ghana and Mali have a defined rotavirus season spanning approximately December to March. In Kenya, rotaviruses circulate all year-around; however, they are more prominent during the months of January and February. So in Ghana, all subjects were enrolled before the rotavirus season started which is in contrast to the subjects enrolled in Mali and Kenya, some of whom were enrolled during the rotavirus season or during the period where rotaviruses circulated more prominently, respectively. This is reflected in the observed low background rates in Ghana (<4%) and high background rates in Mali and Kenya (≥20%). Finally, another important observation is that it is clear that by the time these African subjects received Dose 1, at between 4 and 10 weeks of age, they had little to no pre-existing serum anti-rotavirus IgA as evidenced by the low GMT levels.