Characterization of a novel
ARMA
IgG and IgM antibodies
PF3D7_1136200
Plasmodium falciparum malaria
antigen diversity
protein microarray
vaccines
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2023
2023
Historique:
received:
01
02
2023
accepted:
31
03
2023
medline:
2
5
2023
pubmed:
1
5
2023
entrez:
1
5
2023
Statut:
epublish
Résumé
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. 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. 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. 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.
Identifiants
pubmed: 37122725
doi: 10.3389/fimmu.2023.1156806
pmc: PMC10140549
doi:
Substances chimiques
Antigens, Protozoan
0
Protozoan Proteins
0
Antigens, Surface
0
Malaria Vaccines
0
Immunoglobulin G
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1156806Informations de copyright
Copyright © 2023 Niaré, Chege, Rosenkranz, Mwai, Saßmannshausen, Odera, Nyamako, Tuju, Alfred, Waitumbi, Ogutu, Sirima, Awandare, Kouriba, Rayner and Osier.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest
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