Poster Presentation 16th Lorne Infection and Immunity 2026

Protective Antibody Responses Against Placental Malaria: From Cohort Studies to Monoclonal Antibody Characterization (131599)

Elizabeth Aitken 1 , Vivin Kokuhennadige 1 , Christopher Gonelli 2 , Yvonne Dube 1 , Wina Hasang 1 , Kwok Zi Rou 1 , Akachukwu Onwuka 1 , Niamh Meagher 1 , Megha Rajasekhar 3 , Mwayiwawo Madanitsa 4 , Victor Mwapasa 4 , Kamija Phiri 5 , Phantica Yambo 6 , Paula Tesine 6 , Alice Mengi 6 , Benishar Kombut 6 , Jonathan Kurtis 7 , Morten Nielsen 8 , Stephen Scally 9 , Herbert Opi 10 , Amy Chung 2 , Feiko ter Kuile 11 , Holger Unger 12 , Adam Wheatley 2 , Stephen Rogerson 1
  1. Department of Infectious Diseases, Peter Doherty Institute, University of Melbourne, Melbourne, Victoria, Asutralia
  2. Department of Microbiology and Immunology, Peter Doherty Institute, University of Melbourne, Melbourne, Victoria, Australia
  3. Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia
  4. Malawi University of Science and Technology, Thyolo, Malawi
  5. Kamuzu University of Health Sciences, Malawi
  6. Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea
  7. Brown University, Providence, US
  8. University of Copenhagen, Copenhagen, Denmark
  9. WEHI, Melbourne, Australia
  10. Burnet Institute, Melbourne, Victoria, Australia
  11. Liverpool School of Tropical Medicine, Liverpool
  12. Menzies School of Health Research, Darwin, NT, Australia

We previously identified six antibody features to malaria binding antigen VAR2CSA associated with protection against placental malaria in Papua New Guinea. This current project aimed to 1) confirm whether antibodies to other malaria antigens (besides VAR2CSA) protect against placental malaria, 2) investigate whether the antibody features associated with protection against placental malaria in PNG protect against maternal anaemia in Malawi, and 3) identify and express monoclonal antibodies to VAR2CSA with protective characteristics.

Using multiplex and whole cell assays, we measured ≈150 antibody features in 162 Malawian women mid-pregnancy towards merozoite and infected erythrocyte antigens, comparing levels with and without placental malaria at delivery. We also measured 6 previously identified VAR2CSA antibody features mid-pregnancy in 466 Malawian women with P. falciparum infection during pregnancy, assessing associations with maternal anaemia at delivery. Additionally, we sequenced V(D)J genes and expressed monoclonals using B-cells from PNG women, characterizing these monoclonals against eight heterologous VAR2CSA parasites and conducting phagocytosis and binding inhibition assays.

Of the ≈150 antibody features, only six associated with protection from placental malaria: two were IgG and binding inhibition to the VAR2CSA-expressing parasite, while four targeted merozoite antigens (three being IgA measures). Of the six protective PNG antibody features, only IgG3 to VAR2CSA and phagocytosis of the VAR2CSA-expressing parasite associated with protection from maternal anaemia in Malawi, and only in primigravidae. We produced 16 VAR2CSA monoclonals, all recognized DBL3 or DBL5 subdomains, and some bound all 8 heterologous lines.  None inhibited parasite binding to placental receptors.  Combinations of three but not individual monoclonals could promote phagocytosis.

There is little evidence that non-VAR2CSA antibodies protect against placental malaria and VAR2CSA should be considered further for vaccine development. Cross-reactive antibodies promoting phagocytosis and likely protective and monoclonals with these functions could identify VAR2CSA antigens for vaccines and potential therapeutics.