Characterization of a Novel Plasmodium Falciparum Merozoite Surface Antigen and Potential Vaccine Target
Date
2023
Journal Title
Journal ISSN
Volume Title
Publisher
Frontiers in Immunology
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.
Description
Research Article
Keywords
Plasmodium falciparum malaria, PF3D7_1136200, ARMA, antigen diversity, IgG and IgM antibodies, protein microarray
Citation
Niare´ K, Chege T, Rosenkranz M, Mwai K, Saßmannshausen Z, Odera D, Nyamako L, Tuju J, Alfred T, Waitumbi JN, Ogutu B, Sirima SB, Awandare G, Kouriba B, Rayner JC and Osier FHA (2023) Characterization of a novel Plasmodium falciparum merozoite surface antigen and potential vaccine target. Front. Immunol. 14:1156806. doi: 10.3389/fimmu.2023.1156806