Induction of Strain-Transcending Antibodies Against Group A PfEMP1 Surface Antigens from Virulent Malaria Parasites

• DOI: 10.1371/journal.ppat.1002665
• Publication Date: 2012-04-19T20:52:12Z
• Authors: Ashfaq Ghumra; Jean-Philippe Sem...; Ricardo Ataide; Carolyne Kifude; Yvonne Adams; Antoine Claessens; Damian N. Anong; Peter C. Bull; Clare Fennell; Monica Arman; Alfred Amambua-Ngwa; Michael Walther; David J. Conway; Lalla Kassambara; Ogobara K. Doumbo; Ahmed Raza; J. Alexandra Rowe
• Keywords: Antigenic variation

Sequence diversity in pathogen antigens is an obstacle to the development of interventions against many infectious diseases. In malaria caused by Plasmodium falciparum, PfEMP1 family variant surface encoded var genes are adhesion molecules that play a pivotal role pathogenesis and clinical disease. major target protective immunity, however, drugs or vaccines based on problematic due extensive sequence within family. Here we identified variants transcribed P. falciparum strains selected for virulence-associated phenotype (IgM-positive rosetting). The parasites subset Group A characterised unusual architecture distinct N-terminal domain (either DBLα1.5 DBLα1.8 type). Antibodies raised rabbits domains showed functional activity (surface reactivity with live infected erythrocytes (IEs), rosette inhibition induction phagocytosis IEs) down low concentrations (<10 µg/ml total IgG) homologous parasites. Furthermore, antibodies broad cross-reactivity heterologous parasite same rosetting phenotype, including isolates from four sub-Saharan African countries either (variant HB3var6) TM284var1). These data show share IE epitopes can be targeted strain-transcending PfEMP1. existence shared amongst functionally similar disease-associated suggests therapeutic prevent severe realistic goal.