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Publications

Journal Article Epublish

PubMed: 42504823 DOI: 10.7554/eLife.107603

An abundant merozoite surface protein of Plasmodium falciparum modulates susceptibility to inhibitory antibodies.

Elife 14

Authors: Isabelle G Henshall, Jill Chmielewski, Dimuthu Angage, Ornella Romeo, Keng Heng Lai, Kaitlin R Turland, Nicki Badii, Michael Foley, Robin F Anders, James G Beeson, Danny W Wilson

Affiliations

  • Research Centre for Infectious Diseases, School of Biological Sciences, Adelaide University, Adelaide, Australia.
  • Department of Biochemistry and Chemistry, La Trobe Institute for Molecular Sciences, La Trobe University, Melbourne, Australia.
  • Research Centre for Infectious Diseases, School of Biological Sciences, Adelaide University, Adelaide, Australia. Institute for Photonics and Advanced Sensing (IPAS), Adelaide University, Adelaide, Australia.
  • Institute for Photonics and Advanced Sensing (IPAS), Adelaide University, Adelaide, Australia.
  • AdAlta, Victoria, Australia.
  • Burnet Institute, Melbourne, Australia.
  • Department of Infectious Diseases, University of Melbourne, Melbourne, Australia.
  • School of Translational Medicine and Department of Microbiology, Monash University, Melbourne, Australia.
  • Research Centre for Infectious Diseases, School of Biological Sciences, Adelaide University, Adelaide, Australia. Institute for Photonics and Advanced Sensing (IPAS), Adelaide University, Adelaide, Australia. Burnet Institute, Melbourne, Australia.

Abstract

Malaria merozoite surface proteins (MSPs) are thought to have important roles in red blood cell (RBC) invasion and their exposure on the parasite surface makes them attractive vaccine candidates. However, their role in invasion has not been directly demonstrated and their biological functions remain unknown. One of the most abundant merozoite surface proteins is PfMSP2, a likely ancestral protein that has been maintained in the Plasmodium falciparum lineage and is a focus of vaccine development. Using CRISPR-Cas9 gene editing, we removed PfMSP2 from two different P. falciparum lines with no impact on parasite replication or phenotype in vitro, demonstrating that it is not essential for RBC invasion. Interestingly, loss of PfMSP2 led to increased inhibitory potency of antibodies targeting other merozoite proteins involved in invasion, particularly PfAMA1. In a solid-phase model, increasing concentrations of PfMSP2 protein reduced binding of different antibodies against PfAMA1 in a dose-dependent manner. These data suggest that PfMSP2 can modulate the susceptibility of merozoites to protective inhibitory antibodies. The results of this study change our understanding of the potential functions of PfMSP2 and establish a new concept in malaria where a surface protein can reduce the protective efficacy of antibodies targeting a different antigen. These findings have important implications for understanding malaria immunity and informing vaccine development.

MeSH

Malaria, Merozoites, Vaccines, Antibodies, Microbiology, Parasites, Membrane Proteins, Communicable Diseases, Vaccine Development