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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

Authors

Ashfaq Ghumra

Jean Philippe Semblat

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



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

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Publisher Licence URL
http://creativecommons.org/licenses/by/4.0

Copyright Statement
Copyright: © 2012 Ghumra et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.






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