دورية أكاديمية
Antigenic cartography of immune responses to Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1).
العنوان: | Antigenic cartography of immune responses to Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1). |
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المؤلفون: | Tuju J; KEMRI-Wellcome Trust Research Programme, Kenya.; Department of Chemistry and Biochemistry, Pwani University, Kilifi, Kenya., Mackinnon MJ; KEMRI-Wellcome Trust Research Programme, Kenya., Abdi AI; KEMRI-Wellcome Trust Research Programme, Kenya., Karanja H; KEMRI-Wellcome Trust Research Programme, Kenya., Musyoki JN; KEMRI-Wellcome Trust Research Programme, Kenya., Warimwe GM; KEMRI-Wellcome Trust Research Programme, Kenya.; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Gitau EN; African Population and Health Research Center, Nairobi, Kenya., Marsh K; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Bull PC; KEMRI-Wellcome Trust Research Programme, Kenya., Urban BC; Liverpool School of Tropical Medicine, Department of Tropical Disease Biology, Pembroke Place, Liverpool, United Kingdom. |
المصدر: | PLoS pathogens [PLoS Pathog] 2019 Jul 01; Vol. 15 (7), pp. e1007870. Date of Electronic Publication: 2019 Jul 01 (Print Publication: 2019). |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Public Library of Science Country of Publication: United States NLM ID: 101238921 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7374 (Electronic) Linking ISSN: 15537366 NLM ISO Abbreviation: PLoS Pathog Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: San Francisco, CA : Public Library of Science, c2005- |
مواضيع طبية MeSH: | Antigens, Protozoan/*immunology , Plasmodium falciparum/*immunology , Plasmodium falciparum/*pathogenicity , Protozoan Proteins/*immunology, Amino Acid Sequence ; Antibodies, Protozoan/blood ; Antigenic Variation ; Antigens, Protozoan/genetics ; Child, Preschool ; Epitopes/genetics ; Epitopes/immunology ; Erythrocyte Membrane/immunology ; Erythrocyte Membrane/parasitology ; Female ; Humans ; Infant ; Malaria, Falciparum/immunology ; Malaria, Falciparum/parasitology ; Male ; Plasmodium falciparum/genetics ; Protozoan Proteins/genetics ; Recombinant Proteins/genetics ; Recombinant Proteins/immunology ; Sequence Alignment |
مستخلص: | 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. Competing Interests: The authors have declared that no competing interests exist. |
التعليقات: | Erratum in: PLoS Pathog. 2019 Aug 15;15(8):e1008018. (PMID: 31415664) |
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معلومات مُعتمدة: | 092741 United Kingdom WT_ Wellcome Trust; 084535 United Kingdom WT_ Wellcome Trust; 077176 United Kingdom WT_ Wellcome Trust; United Kingdom WT_ Wellcome Trust; 079082 United Kingdom WT_ Wellcome Trust; 079082 United Kingdom WT_ Wellcome Trust; 084535 United Kingdom WT_ Wellcome Trust |
المشرفين على المادة: | 0 (Antibodies, Protozoan) 0 (Antigens, Protozoan) 0 (Epitopes) 0 (Protozoan Proteins) 0 (Recombinant Proteins) 0 (erythrocyte membrane protein 1, Plasmodium falciparum) |
تواريخ الأحداث: | Date Created: 20190702 Date Completed: 20200102 Latest Revision: 20231012 |
رمز التحديث: | 20240628 |
مُعرف محوري في PubMed: | PMC6625739 |
DOI: | 10.1371/journal.ppat.1007870 |
PMID: | 31260501 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1553-7374 |
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DOI: | 10.1371/journal.ppat.1007870 |