Poster Presentation Lorne Infection and Immunity 2013

Diversity of Plasmodium falciparum var genes: Implications for understanding patterns of antibody acquisition to PfEMP1, the major surface antigen of malaria  (#159)

Sofonias Tessema 1 2 , Stephanie Monk 1 , Digjaya Utama 1 3 , Livingstone Tavul 4 , John C. Reeder 3 5 , Peter Siba 4 , Ivo Mueller 1 2 6 , Alyssa Barry 1 2
  1. The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3052, Australia
  2. Department of Medical Biology, University of Melbourne, Melbourne , Victoria 3052, Australia
  3. Department of Epidemiology and Preventative Medicine, Monash University, Melbourne, Australia
  4. Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea
  5. Centre for Population Health, Burnet Institute, Melbourne, Victoria , Australia
  6. Centre de Recerca en Salut Internacional de Barcelona (CRESIB), Barcelona, Spain

Protective immunity to malaria develops after repeated infection with Plasmodium falciparum and is associated with the acquisition of antibodies to a broad range of variant surface antigens (VSAs). The best-characterized VSA family includes P. falciparum erythrocyte membrane protein 1 (PfEMP1). PfEMP1 proteins are encoded by approximately 60 var genes per haploid genome, and are expressed in a mutually exclusive fashion to mediate antigenic variation and evasion of the host immune response. Although PfEMP1 is the major target of naturally acquired immunity, its potential as a vaccine candidate is problematic because of its large size and extraordinary diversity, which includes up to thousands of variants in some malaria endemic areas. Nevertheless, the diversity of var genes has been shown to be limited in at least one area of Papua New Guinea with an estimated 400variants. The aim of this study was to estimate the extent of var gene diversity in two further parasite populations from PNG. The DBLa domains of the var genes of 70 P. falciparum isolates from PNG (Mugil = 35, Wosera = 35) were PCR amplified, purified, cloned and sequenced. High quality sequences were analyzed to determine the number of unique var genes in the Mugil and Wosera areas and the differences between them. The sequence analysis confirmed that the diversity of var genes is limited in PNG. This provides a framework for understanding patterns of antibody acquisition to the range of PfEMP1 variants circulating in the infecting parasite population.

Key words: Plasmodium falciparum; var genes; VSAs; PfEMP1; anti-PfEMP1 antibody