Antibody to PfEMP1: role in immunity to malaria in children and pregnant women
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Plasmodium falciparum erythrocyte membrane protein 1 is the major binding ligand and major antigen expressed on the surface of infected red blood cells, and is a major target of human immunity. Our work is aiming to identify PfEMP1 types that are associated with specific disease syndromes, and to characterise antibody responses that protect against particular pfEMP1 types and particular disease syndromes.
We use a variety of assays to measure antibody against PfEMP1 types and correlate this with exposure to, or protection from, malaria syndromes. These include malaria in pregnant women, and severe malaria in young children. Assay types include ELISAs; luminex assays (to measuure antibody to multiple PfEMP1 protein fragments simultaneously), assays to measure antibody toPfEMP1 expressed on the surface of infected red blood cells; and antibodies that opsonise infected cells for uptake by phagocytic cells.
Our aim is to identify protective correlates of immunity, and assays that can be deployed tomeasure immunity to PfEMP1 in the context of protection agaist malaria disease
Ms Priyanka Barua, PhD Student
Ms Janavi Jabbarzare, PhD Student
Ms Anjaleena Anthony, PhD Student
Prof James Beeson, Burnet Institue
Dr Michael Duffy, Department of Genetics, The University of Melbourne
Dr Leanne Robinson, PNG Institute of Medical Research
Prof Per Ashorn, University of Tampere, Finland
Prof Ivo Mueller, Walter and Eliza Hall Institute of Medical Research
Dr Laurens Manning, University of Western Australia
Dr Rintis Noviyanti, Eijkman INstitute, Jakarta Indonesia
Prof Terrie Taylor and Dr Karl Seydel, Blantyre Malaria Project, Blantyre Malawi
NHMRC Program Grant 'Understanding malaria in the human host'
A single point in protein trafficking by Plasmodium falciparum determines the expression of major antigens on the surface of infected erythrocytes targeted by human antibodies.
Chan JA, Howell KB, Langer C, Maier AG, Hasang W, Rogerson SJ, Petter M, Chesson J, Stanisic DI, Duffy MF, Cooke BM, Siba PM, Mueller I, Bull PC, Marsh K, Fowkes FJ, Beeson JG.
Cell Mol Life Sci. 2016 May 19. [Epub ahead of print]
Differences in PfEMP1s recognized by antibodies from patients with uncomplicated or severe malaria.
Duffy MF, Noviyanti R, Tsuboi T, Feng ZP, Trianty L, Sebayang BF, Takashima E, Sumardy F, Lampah DA, Turner L, Lavstsen T, Fowkes FJ, Siba P, Rogerson SJ, Theander TG, Marfurt J, Price RN, Anstey NM, Brown GV, Papenfuss AT.
Malar J. 2016 May 5;15(1):258. doi: 10.1186/s12936-016-1296-4.
Differential PfEMP1 expression is associated with cerebral malaria pathology.
Tembo DL, Nyoni B, Murikoli RV, Mukaka M, Milner DA, Berriman M, Rogerson SJ, Taylor TE, Molyneux ME, Mandala WL, Craig AG, Montgomery J.
PLoS Pathog. 2014 Dec 4;10(12):e1004537. doi: 10.1371/journal.ppat.1004537. eCollection 2014 Dec.
PTEX is an essential nexus for protein export in malaria parasites.
Elsworth B, Matthews K, Nie CQ, Kalanon M, Charnaud SC, Sanders PR, Chisholm SA, Counihan NA, Shaw PJ, Pino P, Chan JA, Azevedo MF, Rogerson SJ, Beeson JG, Crabb BS, Gilson PR, de Koning-Ward TF.
Nature. 2014 Jul 31;511(7511):587-91. doi: 10.1038/nature13555. Epub 2014 Jul 16.
Targets of antibodies against Plasmodium falciparum-infected erythrocytes in malaria immunity.
Chan JA, Howell KB, Reiling L, Ataide R, Mackintosh CL, Fowkes FJ, Petter M, Chesson JM, Langer C, Warimwe GM, Duffy MF, Rogerson SJ, Bull PC, Cowman AF, Marsh K, Beeson JG.
J Clin Invest. 2012 Sep;122(9):3227-38. doi: 10.1172/JCI62182. Epub 2012 Aug 1.
Malaria preventive therapy in pregnancy and its potential impact on immunity to malaria in an area of declining transmission.
Teo A, Hasang W, Randall LM, Unger HW, Siba PM, Mueller I, Brown GV, Rogerson SJ.
Malar J. 2015 May 26;14:215. doi: 10.1186/s12936-015-0736-x.
The impact of lipid-based nutrient supplementation on anti-malarial antibodies in pregnant women in a randomized controlled trial.
Chandrasiri UP, Fowkes FJ, Richards JS, Langer C, Fan YM, Taylor SM, Beeson JG, Dewey KG, Maleta K, Ashorn P, Rogerson SJ.
Malar J. 2015 May 10;14:193. doi: 10.1186/s12936-015-0707-2.
Decreasing malaria prevalence and its potential consequences for immunity in pregnant women.
Teo A, Hasang W, Randall LM, Feng G, Bell L, Unger H, Langer C, Beeson JG, Siba PM, Mueller I, Molyneux ME, Brown GV, Rogerson SJ.
J Infect Dis. 2014 Nov 1;210(9):1444-55. doi: 10.1093/infdis/jiu264. Epub 2014 May 5
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