Dataset Information

Characterization of a novel Plasmodium falciparum merozoite surface antigen and potential vaccine target.

ABSTRACT:

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.

SUBMITTER: Niare K

PROVIDER: S-EPMC10140549 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Characterization of a novel <i>Plasmodium falciparum</i> merozoite surface antigen and potential vaccine target.

Niaré Karamoko K Chege Timothy T Rosenkranz Micha M Mwai Kennedy K Saßmannshausen Zoe Z Odera Dennis D Nyamako Lydia L Tuju James J Alfred Tiono T Waitumbi John N JN Ogutu Bernhards B Sirima Sodiomon B SB Awandare Gordon G Kouriba Bourema B Rayner Julian C JC Osier Faith H A FHA

Frontiers in immunology 20230414

<h4>Introduction</h4>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.<h4>Methods</h4>Here, we characterized PF3D7_1136200, which we named Asparagine-Rich Merozoite Antigen (ARMA) based on the analysis of ...[more]

PMID: 37122725

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