IntroductionLive attenuated oral vaccines against rotavirus (RV) have been shown to be less efficacious in children from developing countries. Reasons for this disparity are not fully understood. We assessed the role of maternal factors including breast milk RV-specific IgA, transplacentally acquired infant serum RV-specific IgG and maternal HIV status in seroconversion among Zambian infants routinely immunized with Rotarix™ (RV1).Methods420 mother-child pairs were recruited at infant age 6–12 weeks in Lusaka. Clinical information and samples were collected at baseline and at one month following the second dose of RV1. Determination of breast milk RV-specific IgA and serum RV-specific IgA and IgG was done using standardized ELISA. Seroconversion was defined as a ≥ 4 fold rise in serum IgA titre from baseline to one-month post RV1 dose 2, while seropositivity of IgA was defined as serum titre ≥ 40 and antibody variables were modelled on log-base 2. Logistic regression was used to identify predictors of the odds of seroconversion.ResultsBaseline infant seropositivity was 25.5% (91/357). The seroconversion frequency was 60.2% (130/216). Infants who were IgA seropositive at baseline were less likely to seroconvert compared to their seronegative counterparts (P = 0.04). There was no evidence of an association between maternal HIV status and seroconversion (P = 0.25). Higher titres of breast milk rotavirus-specific IgA were associated with a lower frequency of seroconverson (Nonparametric test for trend Z = -2.84; P<0.01): a two-fold increase in breast milk RV-specific IgA titres was associated with a 22% lower odds of seroconversion (OR = 0.80; 95% CI = 0.68–0.94; P = 0.01). There was seasonal variation in baseline breast milk rotavirus-specific IgA titres, with significantly higher GMTs during the cold dry months (P = 0.01).ConclusionLow immunogenicity of RV1 vaccine could be explained in part by exposure to high antibody titres in breast milk and early exposure to wild-type rotavirus infections. Potential interference of anti-RV specific IgA in breast milk and pre-vaccination serum RV specific-IgA and IgG titres with RV1 seroconversion and effectiveness requires further research.

The role of maternal immunity, received by infants either transplacentally or orally from breast milk, in rotavirus vaccine (RV) performance is evaluated here. Breastfeeding withholding has no effect on vaccine responses, but higher levels of transplacental rotavirus-specific IgG antibody contribute to reduced vaccine seroconversion. The gaps in knowledge on the factors associated with low RV efficacy in low-and middle-income countries (LMIC) remain, and further research is needed to shed more light on these issues. KEYWORDS immunization, low-and middle-income countries, maternal, rotavirus D espite the progress seen with the global introduction of rotavirus vaccines (RV), diarrhea is still a leading cause of death in children under the age of 5 years, and a substantial proportion of disease cases are still attributable to rotavirus infection. The latest estimates show that approximately 215,000 children die each year from rotavirusassociated diarrhea, and approximately 56% of these deaths are in sub-Saharan Africa (1). The World Health Organization (WHO) recommended the introduction of oral RV into national immunization programs (2), and many countries have heeded this call. As of September 2016, the WHO lists 86 countries as having included RV in their national immunization programs, and 6 more are in the course of doing so in 2016 (www.who.int/immunization/monitoring_surveillance/VaccineIntroStatus.pptx). Approximately 50% of the countries in Africa and Asia, over 80% of those in North America, South America, and Australia, and approximately 40% of those in Europe have introduced RV. Following RV introduction, there was a notable reduction in the number of deaths due to diarrhea (1). However, there is consistent evidence from clinical trials that RV have lower efficacies in low-and middle-income countries (LMIC): vaccine efficacies are 80 to 90% in high-income countries (HIC) and 40 to 60% in LMIC (3-8). Indeed, there is growing evidence from vaccine effectiveness studies emerging from the field that in real-life use, vaccine effectiveness is also consistently lower in LMIC (9-12).In addition to the differences in observed vaccine efficacy and effectiveness, there are also marked differences in vaccine-elicited immunity as reported by various vaccine-elicited antibody titers following rotavirus immunization (13)(14)(15)(16)(17)(18). A number of hypotheses have been put forward to explain the differences in efficacy and vaccineelicited immunity between HIC and LMIC. The hypotheses include (i) maternal factors (such as interference from transplacental antibodies and antibody and nonantibody breast milk components [13,[19][20][21][22][23] [38,39]). A better understanding of these factors which decrease the efficacy of RV in LMIC may help to inform interventions to improve efficacy and to further reduce the number of child deaths due to rotavirus disease. This review examines the correlations between maternal immune factors and RV responses and their potential effect on vaccine efficacy. NATURAL ROTAVIRUS...

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