Science Bite (3 minute oral presentation with PPT in live session and poster) - Students, ECRs and EMCRs only 15th Lorne Infection and Immunity 2025

Investigating role of non-VAR2CSA specific antibodies in protection from placental malaria (#310)

Yvonne Dube 1 , Wina Hasang 1 , Mwayiwawo Madanitsa 2 3 , Victor Mwapasa 4 , Jonathan Kurtis 5 , Mortein Nielsen 6 , Stephen Scally 7 , D. Herbert Opi 8 , Kamija Phiri 9 , Feiko O Ter Kuile 3 , Elizabeth H. Aitken 1 10 , Stephen J. Rogerson 1 11
  1. Department of Infectious Diseases, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia
  2. Department of Clinical Sciences, Academy of Medical Sciences, Malawi University of Science and Technology, Thyolo, Malawi
  3. Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom
  4. Department of Epidemiology and Biostatistics, School of Global and Public Health, Kamuzu University of Health Sciences, Blantyre, Malawi
  5. Department of Pathology and Laboratory Medicine, Brown University Medical School, Providence, RI, USA
  6. Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark
  7. Walter and Eliza Hall Institiute of Medical Research, The University of Melbourne, Melbourne, Victoria, Australia
  8. Burnet Institute, Melbourne, Victoria, Australia
  9. Training and Research Unit of Excellence, Blantyre, Malawi
  10. Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia
  11. Department of Medicine (RMH), The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia

Background: Placental malaria (PM), caused by the sequestration of Plasmodium falciparum-infected erythrocytes (IEs) in the placenta via chondroitin sulphate A, often results in adverse pregnancy outcomes. Antibodies targeting VAR2CSA have been associated with protection against PM; however, no VAR2CSA-specific vaccines are available, and the role of other parasite antigen-based vaccines in protection against PM is unclear.

Methods: We investigated if antibodies to non-VAR2CSA antigens contributed to protection from PM. Plasma samples were collected mid-pregnancy from Malawian infected pregnant women, with (n=74) or without evidence of PM (n=88) at delivery. The Luminex multiplex assay was used to quantify antigen-specific IgG, IgG1-4, IgA1, IgA2, IgM, interactions with Fc receptors and C1q to thirteen P. falciparum recombinant antigens. Phagocytosis of merozoites and placental binding IE by THP1 cells and neutrophils, IgG binding to merozoites and to placental binding IE, and levels of adhesion-blocking IgG to placental binding IE, were also measured.

Results: Univariate analysis showed thirty antibody features significantly higher in women with PM (P ≤ 0.05), with twenty-one being antibody features to merozoites and phagocytosis of merozoites by THP-1 and neutrophils. Six antibody features were higher in women with no PM (P ≤ 0.05), including antibodies to VAR2CSA and anti-adhesion antibodies on IEs. Opsonic phagocytosis of IEs by THP-1 cells or of merozoites by neutrophils or antibodies to whole merozoites did not significantly differ between the groups. So far, little evidence was found to suggest that antibodies towards non-VAR2CSA proteins protect against PM. Machine learning identified ten antibody features with 79% predictive accuracy for distinguishing PM or no PM. Antibodies to VAR2CSA measured as IgG binding and, most strongly, binding inhibition were found to be protective from PM.

Conclusion: Antibodies to non-VAR2CSA proteins may be markers of exposure to PM rather than markers of protection.