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

Front Immunol. 2023 Apr 14:14:1156806. doi: 10.3389/fimmu.2023.1156806. eCollection 2023.

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.

Keywords: ARMA; IgG and IgM antibodies; PF3D7_1136200; Plasmodium falciparum malaria; antigen diversity; protein microarray; vaccines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Protozoan / genetics
  • Antigens, Surface
  • Burkina Faso
  • Humans
  • Immunoglobulin G
  • Malaria Vaccines*
  • Malaria, Falciparum*
  • Merozoites
  • Parasites*
  • Plasmodium falciparum
  • Prospective Studies
  • Protozoan Proteins

Substances

  • Antigens, Protozoan
  • Protozoan Proteins
  • Antigens, Surface
  • Malaria Vaccines
  • Immunoglobulin G

Grants and funding

This work was supported through a PhD training fellowship to K.N under a Developing Excellence in Leadership Training and Science (DELTAS) Africa grant (DEL-15-007 and 107755/Z/15/Z: Awandare). The DELTAS Africa programme is an independent funding scheme of The African Academy of Sciences supported by Wellcome and the UK government. FO was supported by Sofja Kovalevskaja Award from the Alexander von Humboldt Foundation (3.2-1184811-KEN-SKP) and an EDCTP Senior Fellowship (TMA 2015 SF1001) which is part of the EDCTP2 programme supported by the European Union.