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Antigenic cartography of immune responses to Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1)

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Tuju, James ORCID: https://orcid.org/0000-0002-0624-1791, Mackinnon, Margaret J. ORCID: https://orcid.org/0000-0003-1279-9625, Abdi, Abdirahman I. ORCID: https://orcid.org/0000-0001-7989-2125, Karanja, Henry, Musyoki, Jennifer N., Warimwe, George M. ORCID: https://orcid.org/0000-0002-4911-6333, Gitau, Evelyn N., Marsh, Kevin ORCID: https://orcid.org/0000-0001-8377-5466, Bull, Peter C. ORCID: https://orcid.org/0000-0002-7674-6752 and Urban, Britta C ORCID: https://orcid.org/0000-0002-4197-8393 (2019) 'Antigenic cartography of immune responses to Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1)'. PLoS Pathogens, Vol 15, Issue 7, e1007870.

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Abstract

Naturally acquired clinical immunity to Plasmodium falciparum is partly mediated by antibodies directed at parasite-derived antigens expressed on the surface of red blood cells which mediate disease and are extremely diverse. Unlike children, adults recognize a broad range of variant surface antigens (VSAs) and are protected from severe disease. Though crucial to the design and feasibility of an effective malaria vaccine, it is not yet known whether immunity arises through cumulative exposure to each of many antigenic types, cross-reactivity
between antigenic types, or some other mechanism. In this study, we measured plasma antibody responses of 36 children with symptomatic malaria to a diverse panel of 36 recombinant proteins comprising part of the DBLα domain (the ‘DBLα-tag’) of PfEMP1, a major class of VSAs. We found that although plasma antibody responses were highly specific to individual antigens, serological profiles of responses across antigens fell into one of just two distinct types. One type was found almost exclusively in children that succumbed to severe disease (19 out of 20) while the other occurred in all children with mild disease (16 out of 16). Moreover, children with severe malaria had serological profiles that were narrower in antigen specificity and shorter-lived than those in children with mild malaria. Borrowing a novel technique used in influenza–antigenic cartography—we mapped these dichotomous serological profiles to amino acid sequence variation within a small sub-region of the PfEMP1 DBLα domain. By applying our methodology on a larger scale, it should be possible to identify epitopes responsible for eliciting the protective version of serological profiles to PfEMP1 thereby accelerating development of a broadly effective anti-disease malaria vaccine.

Item Type: Article
Subjects: QW Microbiology and Immunology > Reference Works. General Immunology > QW 504 General works
QX Parasitology > Protozoa > QX 135 Plasmodia
Faculty: Department: Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI): https://doi.org/10.1371/journal.ppat.1007870
Depositing User: Cathy Waldron
Date Deposited: 03 Jul 2019 15:10
Last Modified: 03 Jul 2019 15:10
URI: https://archive.lstmed.ac.uk/id/eprint/11155

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