Functional Characterization of Plasmodium falciparum Surface-Related Antigen as a Potential Blood-Stage Vaccine Target

J Infect Dis. 2018 Jul 24;218(5):778-790. doi: 10.1093/infdis/jiy222.

Abstract

Plasmodium falciparum erythrocyte invasion is a multistep process that involves a spectrum of interactions that are not well characterized. We have characterized a 113-kDa immunogenic protein, PF3D7_1431400 (PF14_0293), that possesses coiled-coil structures. The protein is localized on the surfaces of both merozoites and gametocytes, hence the name Plasmodium falciparum surface-related antigen (PfSRA). The processed 32-kDa fragment of PfSRA binds normal human erythrocytes with different sensitivities to enzyme treatments. Temporal imaging from initial attachment to internalization of viable merozoites revealed that a fragment of PfSRA, along with PfMSP119, is internalized after invasion. Moreover, parasite growth inhibition assays showed that PfSRA P1 antibodies potently inhibited erythrocyte invasion of both sialic acid-dependent and -independent parasite strains. Also, immunoepidemiological studies show that malaria-infected populations have naturally acquired antibodies against PfSRA. Overall, the results demonstrate that PfSRA has the structural and functional characteristics of a very promising target for vaccine development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Protozoan / blood*
  • Antigens, Protozoan / immunology*
  • Antigens, Protozoan / metabolism
  • Child
  • Child, Preschool
  • Drug Discovery / methods
  • Endocytosis
  • Humans
  • Malaria Vaccines / immunology
  • Malaria, Falciparum / immunology
  • Malaria, Falciparum / prevention & control*
  • Membrane Proteins / immunology*
  • Membrane Proteins / metabolism
  • Plasmodium falciparum / immunology*
  • Protein Binding
  • Protozoan Proteins / immunology*
  • Protozoan Proteins / metabolism

Substances

  • Antibodies, Protozoan
  • Antigens, Protozoan
  • Malaria Vaccines
  • Membrane Proteins
  • Protozoan Proteins