Poster Presentation First Malaria World Congress 2018

Antibody targets on the surface of P. falciparum-infected erythrocytes that are associated with immunity to severe malaria in young children (#251)

Jo-Anne Chan 1 , Michelle J Boyle 1 , Linda Reiling 1 , Zaw Lin 1 , Wina Hasang 2 , Kerryn Moore 1 , Marion Avril 3 , Laurens Manning 4 , Ivo Mueller 5 , Moses Laman 4 , Timothy Davis 6 , Joe D Smith 3 , Stephen J Rogerson 2 , Julie A Simpson 7 , Freya JI Fowkes 1 , James G Beeson 1
  1. Burnet Institute, Melbourne, VIC, Australia
  2. Department of Medicine University of Melbourne, Melbourne
  3. Center for Infectious Diseases Research, Seattle, Washington, USA
  4. Papua New Guinea Institute of Medical Research, Madang
  5. Walter & Eliza Hall Institute, Melbourne
  6. University of Western Australia, Perth, Australia
  7. Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia

Background

Sequestration of P. falciparum-infected erythrocytes (IEs) in the microvasculature contributes to the pathogenesis of severe malaria in children. This mechanism is mediated by PfEMP1 expressed on the IE surface, a major target of naturally acquired antibodies. However, little is known regarding the association between PfEMP1-specific antibodies and protective immunity against severe malaria.

Methods

In a case-control study of young children in Papua New Guinea presenting with severe (SM) or uncomplicated malaria (UM) (n=805), antibody levels were quantified to antigens expressed on the IE surface, using isolates with a virulent phenotype, and to recombinant PfEMP1 domains. We used genetically-modified isolates with suppressed PfEMP1 expression to quantify PfEMP1 as a target of antibodies. Functional antibody responses were quantified using an opsonic phagocytosis assay with monocytes.

Results

Antibodies to the IE surface and recombinant PfEMP1 domains were higher in UM and boosted following infection. We found that PfEMP1 was the major target of antibodies among children with SM and UM, and PfEMP1-specific antibodies were associated with reduced risk of SM. Antibodies mediated opsonic phagocytosis of IEs, which were associated with reduced risk of SM and targeted PfEMP1.

Conclusion

Findings highlight the significance of PfEMP1-specific antibodies in mediating protective immunity against severe malaria in children.