MIG and the Regulatory Cytokines IL-10 and TGF-β1 Correlate with Malaria Vaccine Immunogenicity and Efficacy

Malaria remains one of the world's greatest killers and a vaccine is urgently required. There are no established correlates of protection against malaria either for natural immunity to the disease or for immunity conferred by candidate malaria vaccines. The RTS,S/AS02A vaccine offers significant partial efficacy against malaria. mRNA expression of five key cytokines interferon-gamma (IFN-gamma), monokine induced by gamma (MIG), interleukin-10 (IL-10), transforming growth factor-beta (TGF-beta) and forkhead box P3 (FoxP3) in peripheral blood mononuclear cells were measured by real-time RT-PCR before and after vaccination with RTS, S/AS02A and Modified Vaccinia virus Ankara encoding the circumsporozoite protein (MVA-CS) in healthy malaria-naive adult volunteers. The only significant change was in IFN-gamma mRNA expression, which was increased seven days after vaccination (P = 0.04). Expression of MIG mRNA seven days after vaccination correlated inversely with time to detection of parasites by blood film in an experimental sporozoite challenge (r = 0.94 P = 0.005). An inverse relationship was seen between both TGF-beta 1 and IL-10 mRNA at baseline and the anti-circumsporozoite IgG antibody response (r = -0.644 P = 0.022 and r = -0.554 P = 0.031 respectively). This study demonstrates the potential for MIG expression as a correlate of protection against malaria. Baseline levels of the regulatory cytokines TGF-beta and IL-10 inversely correlated with antibody levels post vaccination and warrant further studies to improve understanding of individual differences in response to vaccination.