Significances refer to the statistical interaction between the effects of EBV and CMV contamination. The EBV+CMVgroup accounted for only 8 of the 161 (5.0%) classifiable infants at nine months and 13 of 159 (8.2%) at eleven months. with EBV had reduced IgG and IgM antibody responses to meningococcal polysaccharides and to measles vaccine. Contamination with CMV alone predicted no changes in the response to meningococcal polysaccharide. While CMV alone had no discernable effect on the antibody response to measles, the response of infants infected with both CMV and EBV was similar to that of infants infected with neither, suggesting that the effects of CMV contamination countered the effects of EBV on measles antibody responses. == Conclusions == The results of this exploratory study indicate that contamination with EBV is usually associated with reduced antibody responses to polysaccharides and to measles vaccine, but suggest that the response to T-cell dependent antigens such as measles haemagglutinin may be restored by contamination with CMV. == Introduction == Infant vaccination is one of the most important strategies to combat infectious disease worldwide. However, it has been known for four decades that the efficacy of infant vaccines in Sub-Saharan Africa is lower than in high income settings[1]and that intercurrent infections like malaria may influence antibody responses[2],[3]. For instance, the efficacy of the live attenuated measles vaccine is typically over 90% in Europe and North America[4][6], but below 70% in West SCH58261 Africa[7][9]. In Sub-Saharan Africa, contamination with the herpesviruses Epstein-Barr computer virus (EBV) and cytomegalovirus (CMV) usually occurs during infancy[10][12], after which they establish lifelong contamination[13],[14]. Although contamination is usually asymptomatic, both viruses have powerful effects around the lymphocyte populations involved in vaccine-mediated immunity. EBV infects B-cells and during acute SCH58261 contamination, up to 50% of B-cells may be infected[15]. While EBV contamination is usually asymptomatic in healthy individuals, it can cause severe disease in immunocompromised individuals and coupled with chromosomal translocations, causes SCH58261 Burkitt’s lymphoma Burkitt’s lymphoma in infants whose immune systems have been suppressed by malaria[16],[17]. In the absence of disease, EBV infected B-cells accumulate a relatively high number of mutations which suggests that EBV may influence the B-cell compartment even in the absence of clinical disease[18]. The effect of EBV contamination on B-cell responses to vaccines or concurrent infections is usually unknown. Unlike EBV, CMV has a powerful influence on T-cells even though T-cells are not a major target for CMV Mouse monoclonal to ABCG2 contamination[19]. The T-cell populations of CMV-infected individuals show considerably higher levels of differentiation[20][23], even among young infants who are still receiving childhood vaccinations[24]. These effects vary with age as CMV-induced differentiation in the elderly is associated with reduced subpopulations of nave T-cells and poor vaccine responses[23],[25], but infected infants show no such evidence of reduction of the nave T-cell pool or of CMV-associated reduction in T-cell response to measles vaccine[26]. Polysaccharide vaccines stimulate B-cells independently of T-cells, suggesting that they may be particularly vulnerable to modulation by EBV. Although the meningococcus polysaccharide does not induce lasting immunity if administered before four years[27], the WHO still recommends vaccination irrespective of age to contain the outbreaks of meningococcal meningitis that periodically sweep the Sub-Saharan meningitis belt[28],[29]and so it remains a valuable tool in child health. By contrast, the live attenuated measles vaccine induces a broad range of T-cell and antibody responses[30],[31]so is unlikely to be so vulnerable to any one mechanism of modulation. As early life CMV and EBV contamination and relatively low vaccine efficacy are both characteristic of Sub-Saharan Africa, we hypothesised an association between CMV and EBV contamination in infancy and reduced antibody responses to vaccines. We therefore quantified their influence on antibody responses to the polysaccharide vaccine againstNeisseria meningitidis(meningococcus) and the live attenuated measles vaccine. We recruited infants from an ongoing cohort in a peri-urban area of The.