Oral Presentation Lorne Infection and Immunity 2018

Insights into the malaria immunome by combining population genomics and sero-epidemiology (#10)

Sofonias K Tessema 1 2 , Thomas Lavstsen 3 , Peter M Siba 4 , Diana Hansen 1 5 , Andrew Oleinikov 6 , Dominic Kwiatkowski 7 8 , Phillip Felgner 9 , Denise L Doolan 10 , Ivo Mueller 1 2 , Alyssa E Barry 1 2
  1. Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia
  2. Division of Population Health and Immunity, Walter and Eliza Hall Institute for Medical Research, Melbourne, Victoria, Australia
  3. University of Copenhagen, Copenhagen, Denmark
  4. Papua New Guinea Institute of Medical Research, Goroka, Eastern Highlands Province, Papua New Guinea
  5. Division of Infection and Immunity, Walter and Eliza Hall Institute for Medical Research, Melbourne, Victoria, Australia
  6. Department of Microbiology and Immunology, Florida Atlantic University, Boca Raton, Florida, United States
  7. Wellcome Trust Sanger Institute, Hinxton, United Kingdom
  8. MRC Centre for Genomics and Global Health, University of Oxford, Oxford, United Kingdom
  9. Department of Medicine (Division of Infectious Diseases), University of California Irvine, Irvine, California, United States
  10. James Cook University, Cairns, Queensland, Australia

The causative agent of malaria, Plasmodium falciparum, harnesses population-level genetic diversity as a strategy to evade host immunity. The highly polymorphic major surface antigen PfEMP1 is a major target of naturally acquired host immunity and an important virulence determinant. However, with approximately 60 variants per parasite genome, and thousands of variants at the population level, candidate PfEMP1 molecules for vaccine development have been elusive. We have conducted a series of studies to characterise naturally acquired anti-PfEMP1 antibody responses to more than 500 PfEMP1 variants, including those collected from local parasite populations. Investigations of antibody responses in young Papua New Guinean children in association with prospective risk of malaria has enabled the identification of putative biomarkers of protection against clinical and severe malaria. Genomic sequencing of 150 P. falciparum isolates allowed full-length PfEMP1 variants circulating in the PNG parasite population to be defined, and has revealed the structure and function of potential biomarker targets. These insights into the malaria immunome suggest that specific subclasses of PfEMP1 may be targets of protective host immunity, and identify putative biomarkers of population level immunity to malaria.