Late-breaking Poster Asia-Pacific Vaccine and Immunotherapy Congress 2024

Association of Plasmodium falciparum specific afucosylated IgG with placental malaria protection (#149)

HongHua Ding 1 , Wina Hasang 1 , Bruce Wines 2 , Mwayiwawo Madanitsa 3 4 , Victor Mwapasa 5 , Kamija Phiri 6 , Feiko O ter Kuile 4 , Elizabeth Aitken 1 7 , Stephen Rogerson 1 8
  1. Department of Infectious Diseases, The University of Melbourne, The Peter Doherty Institue, Melbourne, VIC, Australia
  2. Immune Therapies Group, Burnet Institute, Melbourne, VIC
  3. Department of Clinical Sciences, Academy of Medical Sciences, Malawi University of Science and Technology, Thyolo, Malawi
  4. Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom
  5. Department of Epidemiology and Biostatistics, School of Global and Public Health, Kamuzu University of Health Sciences, Blantyre, Malawi
  6. Training and Research Unit of Excellence, Blantyre, Malawi
  7. Department of Microbiology and Immunology, The University of Melbourne, The Peter Doherty Institute, Melbourne, Australia
  8. Department of Medicine (RMH), The University of Melbourne, Melbourne, Australia

Malaria is a life-threatening disease that causes over 600,000 deaths annually, with the most severe form caused by Plasmodium falciparum. In addition to neutralizing activities, naturally acquired immunoglobulin G (IgG) antibodies serve a critical role in the activation of immune-protective functions via the Fc-gamma receptors (FcγR). The recent focus on IgG fucosylation highlighted the heightened binding affinity of afucosylated IgG to FcγRIIIa compared to the normally fucosylated IgG, resulting in enhanced antibody dependent cellular cytotoxicity (ADCC). This is due to the absence of fucose on the highly conserved N-linked glycan located in the Fc domain of IgG. In this study, we utilized the Fucose-sensitive Enzyme-linked immunosorbent assay (ELISA) for Antigen-Specific IgG (FEASI), an immunoassay that is capable of quantifying Fc fucosylation of antigen-specific IgG antibodies. FEASI consists of two ELISA assays; the first is to measure the levels of antigen-specific IgG independent of fucosylation using total IgG, while the second gives FcγRIIIa specific binding readouts which is highly sensitive to IgG fucosylation. The output of both ELISAs is converted into a ratio that represents the level of afucosylated IgG in a given sample. Here we examined the plasma from N=163 P. falciparum infected pregnant Malawian women with or without evidence of placental malaria at delivery using FEASI. Our results showed significantly higher levels of antigen-specific afucosylated IgG in women without evidence of placental malaria at delivery (p < 0.001). This finding suggests that afucosylated IgG levels could be a marker for protection and further experiments will explore the association between the levels of afucosylated IgG with neutrophil phagocytosis and NK cell activation against malaria infected erythrocytes, and validate these observations in a further sample set. These results have important implications in the understanding of naturally acquired protection against malaria in pregnant women.