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

Investigating role of non-VAR2CSA specific antibodies in protection from placental malaria (#148)

Yvonne Dube 1 , Wina Hasang 1 , Mwayiwawo Madanitsa 2 3 , Victor Mwapasa 4 , Jonathan Kurtis 5 , Morten Nielsen 6 , Stephen Scally 7 , 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

Placental malaria (PM) is caused by Plasmodium falciparum-infected erythrocytes (IEs) sequestration in placenta via chondroitin sulphate A 1 , and antibodies to VAR2CSA have been associated with protection from PM and adverse pregnancy outcomes 2,4. There are no VAR2CSA specific vaccines available, whereas vaccines based on other parasite antigens have progressed to clinical trials 3,5. Their role in protection against PM is unclear.

We investigated whether antibodies to antigens other than VAR2CSA contributed to protection from PM. We also evaluated opsonic phagocytosis of whole IEs and merozoites by THP-1 cells and neutrophils respectively. IgG and adhesion-blocking IgG to placental binding IE were also assessed.

Plasma collected mid-pregnancy from infected pregnant women from Malawi, who had (n=75) or did not have evidence of PM (n=88) at delivery, was used to measure antigen-specific IgG, IgG1-4, IgA1, IgA2, IgM and interactions with Fc features and C1q to thirteen P. falciparum recombinant antigens including 8 merozoite, 2 schizont stage; 2 pregnancy specific (VAR2CSA) and 1 sporozoite antigen. IgG binding to merozoites and to placental binding IE and phagocytosis of merozoites and placental binding IE by THP1 cells and neutrophils was also measured. Levels of adhesion-blocking IgG to placental binding IE were also measured. Welch’s t test was performed, and a volcano plot generated to visualize distribution of differences in antibody features between the two groups. A correlation network was generated to visualize the data. 

Twenty-seven antibody features were higher in women with PM (P ≤ 0.05), with nineteen being antibody features to merozoites (IgG to MSP3, PfRh5; IgG1to AMA1, EBA175, MSP1-p19, MSP2, PfRh2a1; IgG3 to MSP3; FcγRIIA to AMA1; FcγRIIIA to AMA1; FcγRIIB to AMA1, MSP1-p19, MSP3, FcγRIIIB to AMA1, MSP3; IgA2 to AMA1, MSP1-p19; C1q to AMA1, PfRh2a1. Five antibody features were higher in pregnant women with no placental malaria (P ≤ 0.05), including IgA1 antibodies to MSP2, MSP9, PfRh2a1, PfRh5 and complement binding antibodies to PfRh5, as were antibodies to VAR2CSA and adhesion-blocking antibodies on IEs. Phagocytosis of opsonised IEs by THP-1 cells or of merozoites by neutrophils did not significantly differ between the groups.

Little evidence regarding the role of antibodies towards non-VAR2CSA proteins in protection from PM was observed. The recognition and binding inhibition assays indicate that the antibodies to VAR2CSA in the no PM group are protective. Univariate analysis suggests that antibodies to non-VAR2CSA proteins may be markers of exposure to PM rather than markers of protection.

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