MIG and the Regulatory Cytokines IL-10 and TGF-b1 Correlate with Malaria Vaccine Immunogenicity and Efficacy

Abstract

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-c), monokine induced by gamma (MIG), interleukin-10 (IL-10), transforming growth factor-b (TGF-b) 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-naı̈ve adult volunteers. The only significant change was in IFN-c 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-b1 and IL-10 mRNA at baseline and the anti-circumsporozoite IgG antibody response (r =20.644 P = 0.022 and r =20.554 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-b and IL-10 inversely correlated with antibody levels post vaccination and warrant further studies to improve understanding of individual differences in response to vaccination. Citation: Dunachie SJ, Berthoud T, Keating SM, Hill AVS, Fletcher HA (2010) MIG and the Regulatory Cytokines IL-10 and TGF-b1 Correlate with Malaria Vaccine Immunogenicity and Efficacy. PLoS ONE 5(9): e12557. doi:10.1371/journal.pone.0012557 Editor: Aric Gregson, University of California Los Angeles, United States of America Received February 17, 2010; Accepted July 13, 2010; Published September 3, 2010 Copyright: 2010 Dunachie et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: Supported by funding from the Wellcome Trust, the UK Medical Research Council, the PATH Malaria Vaccine Initiative and an NIHR award to the Oxford Biomedical Research Centre. AVSH is a Wellcome Trust Principal Research Fellow and SJD was an MRC Clinical Fellow when most of this work was performed. SJD is now an Academic Clinical Lecturer at Oxford University Clinical Academic Graduate School (OUCAGS@medsci.ox.ac.uk). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: susie.dunachie@ndm.ox.ac.uk

6 Figures and Tables

Cite this paper

@inproceedings{Dunachie2017MIGAT, title={MIG and the Regulatory Cytokines IL-10 and TGF-b1 Correlate with Malaria Vaccine Immunogenicity and Efficacy}, author={Susanna J. Dunachie and Tamara K Berthoud and Sheila M Keating and Adrian V S Hill and Helen A Fletcher and Aric L Gregson}, year={2017} }