In industrialized settings, both offered excellent protection (>85%) against severe rotavirus disease during the first and second year of life, from a broad range of commonly

circulating strains [2], [3], [8] and [9]. In developing country settings, however, vaccine protection has been somewhat lower [5], [6] and [11]. Furthermore, in Africa, the efficacy in the second year of life (∼20%) was lower than that observed in the first year of life (∼64%), possibly due to a lower initial vaccine immune response that may wane more rapidly [5], [6] and [7]. The vaccines have also shown good effectiveness against severe rotavirus gastroenteritis when utilized in routine immunization programs [12]. Historically, the potency of live oral vaccines, including

rotavirus vaccines [7] and [13], oral poliovirus vaccine (OPV) [14] and [15], cholera vaccines [16], [17] and [18], and other candidate rotavirus FLT3 inhibitor vaccines has been lower in developing countries. This problem of lower immunogenicity to live oral vaccines in developing countries was initially identified by Jacob John, who showed significantly lower immune responses to oral poliovirus vaccine (OPV) in Indian children selleck chemical compared to that observed in developed countries [14]. Mucosal immunity induced by some OPV formulations has also been lower in northeastern regions of India where vaccine efficacy has been significantly lower compared to other regions

of India [19]. The lower potency of live oral vaccines enough in developing countries could potentially be explained by several reasons as described elsewhere [13], [20] and [21], including higher titres of maternal antibodies [22], breastfeeding [23], prevalent viral and bacterial gut infections [21] and [24], and micronutrient deficiency [25]. An additional question for rotavirus vaccines is the concomitant administration of a competing oral vaccine (OPV) in the same age group and same schedule. For rotavirus vaccines, the potential interference from the simultaneous administration of OPV has been highlighted as one putative reason for lower rotavirus vaccine efficacy in the poorest settings compared with developed settings where inactivated poliovirus vaccine (IPV) is primarily used [20] and [26]. According to WHO, over 140 countries are currently using OPV as part of their routine immunization program [27]. Because both OPV and rotavirus vaccines contain live, attenuated vaccine virus strains that replicate in the gut, the potential for mutual interference exists. In a review by Rennels of co-administration of OPV with earlier rotavirus vaccines tested in the 1980s and 1990s, OPV appeared to interfere with the serum immune response to rotavirus vaccines [20]. However, because the studies were small, the effect was usually not statistically significant and largely overcome by subsequent rotavirus vaccine doses.