Induction of strain-transcending antibodies against group A PfEMP1 surface antigens from virulent malaria parasites

Ghumra, Ashfaq; Semblat, Jean Philippe; Ataide, Ricardo; Kifude, Carolyne; Adams, Yvonne; Claessens, Antoine; Anong, Damian N.; Bull, Peter C.; Fennell, Clare; Arman, Monica; Amambua-Ngwa, Alfred; Walther, Michael; Conway, David J.; Kassambara, Lalla; Doumbo, Ogobara K.; Raza, Ahmed; Rowe, J. Alexandra

Abstract

Sequence diversity in pathogen antigens is an obstacle to the development of interventions against many infectious diseases. In malaria caused by Plasmodium falciparum, the PfEMP1 family of variant surface antigens encoded by var genes are adhesion molecules that play a pivotal role in malaria pathogenesis and clinical disease. PfEMP1 is a major target of protective immunity, however, development of drugs or vaccines based on PfEMP1 is problematic due to extensive sequence diversity within the PfEMP1 family. Here we identified the PfEMP1 variants transcribed by P. falciparum strains selected for a virulence-associated adhesion phenotype (IgM-positive rosetting). The parasites transcribed a subset of Group A PfEMP1 variants characterised by an unusual PfEMP1 architecture and a distinct N-terminal domain (either DBLα1.5 or DBLα1.8 type). Antibodies raised in rabbits against the N-terminal domains showed functional activity (surface reactivity with live infected erythrocytes (IEs), rosette inhibition and induction of phagocytosis of IEs) down to low concentrations (

Citation

Ghumra, A., Semblat, J. P., Ataide, R., Kifude, C., Adams, Y., Claessens, A., Anong, D. N., Bull, P. C., Fennell, C., Arman, M., Amambua-Ngwa, A., Walther, M., Conway, D. J., Kassambara, L., Doumbo, O. K., Raza, A., & Rowe, J. A. (2012). Induction of strain-transcending antibodies against group A PfEMP1 surface antigens from virulent malaria parasites. PLoS Pathogens, 8(4), Article e1002665. https://doi.org/10.1371/journal.ppat.1002665

• Journal Article Type: Article
• Acceptance Date: Mar 8, 2012
• Online Publication Date: Apr 19, 2012
• Publication Date: Apr 1, 2012
• Deposit Date: May 5, 2022
• Publicly Available Date: Sep 12, 2022
• Journal: PLoS Pathogens
• Print ISSN: 1553-7366
• Electronic ISSN: 1553-7374
• Publisher: Public Library of Science
• Peer Reviewed: Peer Reviewed
• Volume: 8
• Issue: 4
• Article Number: e1002665
• DOI: https://doi.org/10.1371/journal.ppat.1002665
• Public URL: https://hull-repository.worktribe.com/output/3571166