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Conference Agenda

Overview and details of the sessions of this conference. Please select a date or location to show only sessions at that day or location. Please select a single session for detailed view (with abstracts and downloads if available).

Daily Overview

Session

CP19.1: Immunology 2 - 10 min talks
Location: Lecture Theatre 2
Session Chair: Alicja (Ala) Tabor, The University Of Queensland
Session Chair: Hannah Siddle, The University of Queensland

Presentation 1

Afucosylated VAR2CSA-specific IgG reduce risks of placental malaria

HongHua Ding¹, Oscar H. Lloyd Williams¹, Maria Saeed¹, Wina Hasang¹, Bruce D. Wines², Mary Lopez-Perez³, Maria del Pilar Quintana³, Lars Hviid³, Adam Wheatley⁴, Mwayiwawo Madanitsa^5,6, Victor Mwapasa⁷, Kamija S. Phir^7,8, Feiko O. ter Kuile⁶, Nichollas Scott⁴, Elizabeth H. Aitken^1,4, Stephen J. Rogerson^1,9

1: Department of Infectious Diseases, The University of Melbourne, The Peter Doherty Institute, Melbourne 3000, Victoria, Australia; 2: Immune Therapies Group, Burnet Institute, Melbourne 3004, Victoria, Australia.; 3: Centre for Translational Medicine and Parasitology, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark. ; 4: Department of Microbiology and Immunology, The University of Melbourne, The Peter Doherty Institute, Melbourne 3000, Victoria, Australia; 5: Department of Clinical Sciences, Academy of Medical Sciences, Malawi University of Science and Technology, Limbe, Malawi.; 6: Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool L3 5QA, United Kingdom.; 7: Department of Epidemiology and Biostatistics, School of Global and Public Health, Kamuzu University of Health Sciences, Blantyre 3, Malawi.; 8: Training and Research Unit of Excellence, Blantyre 3, Malawi.; 9: Department of Medicine (RMH), The University of Melbourne, Melbourne 3000, Victoria, Australia.

Antibody Fc regions have important roles in clearance of Plasmodium falciparum infected erythrocytes. One such role is engagement with Fcg receptors on host leukocytes. In the case of FcgRIIIa and b, this interaction is greatly enhanced when the IgG glycan is afucosylated. In this study, we used a fucose-sensitive enzyme-linked immunosorbent assay, FEASI, to assess afucosylation in IgG specific for placental malaria protein VAR2CSA from n=139 malaria-exposed pregnant Malawian women, correlating these data with mass spectrometry-based analysis. Furthermore, we measured the effect of afucosylation on Fc-mediated leukocyte functions, using both plasma and a monoclonal antibody, PAM2.8, with varying levels of afucosylation.

Results showed significantly higher levels of VAR2CSA-specific IgG afucosylation in women with no placental malaria measured by FEASI (p < 0.0001), which correlated strongly with mass spectrometry analysis (R = 0.8, p < 0.0001). In addition, highly afucosylated IgG mediated significantly greater neutrophil phagocytosis of antigen coated beads and induction of NK cell degranulation by IEs.

Afucosylated IgG to VAR2CSA, measured by FEASI or mass spectrometry, was a correlate of protection from placental malaria, and afucosylated IgG activated NK cells and neutrophils. Naturally acquired or therapeutic afucosylated IgG antibody could have a role in protection from malaria infection.