title: MIG and the regulatory cytokines IL-10 and TGF-β1 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-γ), monokine induced by gamma (MIG), interleukin-10 (IL-10), transforming growth factor-β (TGF-β) 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-naïve adult volunteers. The only significant change was in IFN-γ 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-β1 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-β and IL-10 inversely correlated with antibody levels post vaccination and warrant further studies to improve understanding of individual differences in response to vaccination.
authors.affiliation: Centre for Clinical Vaccinology and Tropical Medicine, The Jenner Institute, University of Oxford, Oxford, United Kingdom. susie.dunachie@ndm.ox.ac.uk
authors.forename: Susanna J
authors.initials: SJ
authors.lastname: Dunachie
authors.forename: Tamara
authors.initials: T
authors.lastname: Berthoud
authors.forename: Sheila M
authors.initials: SM
authors.lastname: Keating
authors.forename: Adrian V S
authors.initials: AV
authors.lastname: Hill
authors.forename: Helen A
authors.initials: HA
authors.lastname: Fletcher
mesh_terms: D000913:Antibodies, Protozoan / Q000276:immunology; D054370:Chemokine CXCL9 / Q000235:genetics / Q000276:immunology*; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology*; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control; D010963:Plasmodium falciparum / Q000276:immunology; D015800:Protozoan Proteins / Q000008:administration & dosage / Q000276:immunology; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000276:immunology*
chemical_list: D000913:Antibodies, Protozoan; D054370:Chemokine CXCL9; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10; D007371:Interferon-gamma