Characterization of a novel Plasmodium falciparum merozoite surface antigen and potential vaccine target
Copyright © 2023 Niaré, Chege, Rosenkranz, Mwai, Saßmannshausen, Odera, Nyamako, Tuju, Alfred, Waitumbi, Ogutu, Sirima, Awandare, Kouriba, Rayner and Osier..
Introduction: Detailed analyses of genetic diversity, antigenic variability, protein localization and immunological responses are vital for the prioritization of novel malaria vaccine candidates. Comprehensive approaches to determine the most appropriate antigen variants needed to provide broad protection are challenging and consequently rarely undertaken.
Methods: Here, we characterized PF3D7_1136200, which we named Asparagine-Rich Merozoite Antigen (ARMA) based on the analysis of its sequence, localization and immunogenicity. We analyzed IgG and IgM responses against the common variants of ARMA in independent prospective cohort studies in Burkina Faso (N = 228), Kenya (N = 252) and Mali (N = 195) using a custom microarray, Div-KILCHIP.
Results: We found a marked population structure between parasites from Africa and Asia. African isolates shared 34 common haplotypes, including a dominant pair although the overall selection pressure was directional (Tajima's D = -2.57; Fu and Li's F = -9.69; P < 0.02). ARMA was localized to the merozoite surface, IgG antibodies induced Fc-mediated degranulation of natural killer cells and strongly inhibited parasite growth in vitro. We found profound serological diversity, but IgG and IgM responses were highly correlated and a hierarchical clustering analysis identified only three major serogroups. Protective IgG and IgM antibodies appeared to target both cross-reactive and distinct epitopes across variants. However, combinations of IgG and IgM antibodies against selected variants were associated with complete protection against clinical episodes of malaria.
Discussion: Our systematic strategy exploits genomic data to deduce the handful of antigen variants with the strongest potential to induce broad protection and may be broadly applicable to other complex pathogens for which effective vaccines remain elusive.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
Frontiers in immunology - 14(2023) vom: 14., Seite 1156806 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Niaré, Karamoko [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 02.05.2023 Date Revised 02.05.2023 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.3389/fimmu.2023.1156806 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM356261077 |
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| 100 | 1 | |a Niaré, Karamoko |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Characterization of a novel Plasmodium falciparum merozoite surface antigen and potential vaccine target |
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| 500 | |a Date Revised 02.05.2023 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 Niaré, Chege, Rosenkranz, Mwai, Saßmannshausen, Odera, Nyamako, Tuju, Alfred, Waitumbi, Ogutu, Sirima, Awandare, Kouriba, Rayner and Osier. | ||
| 520 | |a Introduction: Detailed analyses of genetic diversity, antigenic variability, protein localization and immunological responses are vital for the prioritization of novel malaria vaccine candidates. Comprehensive approaches to determine the most appropriate antigen variants needed to provide broad protection are challenging and consequently rarely undertaken | ||
| 520 | |a Methods: Here, we characterized PF3D7_1136200, which we named Asparagine-Rich Merozoite Antigen (ARMA) based on the analysis of its sequence, localization and immunogenicity. We analyzed IgG and IgM responses against the common variants of ARMA in independent prospective cohort studies in Burkina Faso (N = 228), Kenya (N = 252) and Mali (N = 195) using a custom microarray, Div-KILCHIP | ||
| 520 | |a Results: We found a marked population structure between parasites from Africa and Asia. African isolates shared 34 common haplotypes, including a dominant pair although the overall selection pressure was directional (Tajima's D = -2.57; Fu and Li's F = -9.69; P < 0.02). ARMA was localized to the merozoite surface, IgG antibodies induced Fc-mediated degranulation of natural killer cells and strongly inhibited parasite growth in vitro. We found profound serological diversity, but IgG and IgM responses were highly correlated and a hierarchical clustering analysis identified only three major serogroups. Protective IgG and IgM antibodies appeared to target both cross-reactive and distinct epitopes across variants. However, combinations of IgG and IgM antibodies against selected variants were associated with complete protection against clinical episodes of malaria | ||
| 520 | |a Discussion: Our systematic strategy exploits genomic data to deduce the handful of antigen variants with the strongest potential to induce broad protection and may be broadly applicable to other complex pathogens for which effective vaccines remain elusive | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a ARMA | |
| 650 | 4 | |a IgG and IgM antibodies | |
| 650 | 4 | |a PF3D7_1136200 | |
| 650 | 4 | |a Plasmodium falciparum malaria | |
| 650 | 4 | |a antigen diversity | |
| 650 | 4 | |a protein microarray | |
| 650 | 4 | |a vaccines | |
| 650 | 7 | |a Antigens, Protozoan |2 NLM | |
| 650 | 7 | |a Protozoan Proteins |2 NLM | |
| 650 | 7 | |a Antigens, Surface |2 NLM | |
| 650 | 7 | |a Malaria Vaccines |2 NLM | |
| 650 | 7 | |a Immunoglobulin G |2 NLM | |
| 700 | 1 | |a Chege, Timothy |e verfasserin |4 aut | |
| 700 | 1 | |a Rosenkranz, Micha |e verfasserin |4 aut | |
| 700 | 1 | |a Mwai, Kennedy |e verfasserin |4 aut | |
| 700 | 1 | |a Saßmannshausen, Zoe |e verfasserin |4 aut | |
| 700 | 1 | |a Odera, Dennis |e verfasserin |4 aut | |
| 700 | 1 | |a Nyamako, Lydia |e verfasserin |4 aut | |
| 700 | 1 | |a Tuju, James |e verfasserin |4 aut | |
| 700 | 1 | |a Alfred, Tiono |e verfasserin |4 aut | |
| 700 | 1 | |a Waitumbi, John N |e verfasserin |4 aut | |
| 700 | 1 | |a Ogutu, Bernhards |e verfasserin |4 aut | |
| 700 | 1 | |a Sirima, Sodiomon B |e verfasserin |4 aut | |
| 700 | 1 | |a Awandare, Gordon |e verfasserin |4 aut | |
| 700 | 1 | |a Kouriba, Bourema |e verfasserin |4 aut | |
| 700 | 1 | |a Rayner, Julian C |e verfasserin |4 aut | |
| 700 | 1 | |a Osier, Faith H A |e verfasserin |4 aut | |
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