There is also evidence of a strong genetic contribution to circulating TGF-b1 levels. There is a wide variation in TGF-b levels within and between populations, for example levels of duodenal TGF-b+cells in rural Gambian infants are up to ten times higher than in UK controls. We hypothesise that levels of TGF-b may be related to immune responses to vaccination. In a murine model of malaria a relationship between response to vaccination, gut parasite infestation and TGF-b1 levels has been reported. Parallel studies in our laboratory have demonstrated down-regulation of TGF-b1 and increased IFN-c ELISPOT responses following boosting of BCG high content screening inhibitor vaccinated subjects with the novel tuberculosis vaccine MVA-85A. Due to limited cell numbers we were unable to confirm if regulatory T cells were influencing the vaccine induced immune response or protection from disease. Although protection induced by vaccination with RTS,S is partial it remains the best performing candidate malaria vaccine in the world. There has been no immune correlate of protection identified for RTS,S to date although both antibodies, and possibly also T cells, are thought to be important for protection. Our results support the view that a functional IFN-c immune response is important for protection induced by RTS,S although whether this would work by a direct effect of cellular immunity at the liver-stage or by modulating the quality of protective antibodies induced remains unclear. The role of the MVA-CS vaccine cannot be fully ascertained in this study. MVACS neither induced nor boosted antibody responses and there was no evidence of improvement in efficacy compared to RTS,S used alone in other studies. IL-10 and TGF-b1 may play a dual role in the attenuation of both protective T cell and IgG antibody responses induced by vaccination, and suggest pathways for the next generation of vaccines to target to enhance responses. This study was based on mRNA measurement in relatively small cell numbers, giving potential for development of monitoring assays using fingerprick blood samples suitable for field trials. An immune correlate of protection would greatly facilitate the development and testing of new malaria vaccines. Our findings, in such a small dataset of twelve subjects, need to be confirmed in a larger challenge study cohort and in a field setting and more detailed analysis of the pathways involved is required. In particular the impact of baseline IL-10 and TGF-beta levels on the induction of antibodies in African populations could be assessed by monitoring volunteer samples collected prior to vaccination with RTS,S and other candidate malaria vaccines. The feasibility of mRNA profiling to assess immune responses in an African vaccine trial has been demonstrated. Factors affecting the development of protective immune responses following vaccination with RTS,S/AS02A are of considerable interest to the vaccine community as further elucidation of these mechanisms could hold the key to understanding why some individuals acquire effective immunity.