Basigin is a druggable target for host-oriented antimalarial interventions. Academic Article uri icon

Overview

MeSH

  • Animals
  • Base Sequence
  • Carrier Proteins
  • Cloning, Molecular
  • Erythrocytes
  • Mice
  • Molecular Sequence Data
  • Sequence Analysis, DNA
  • Surface Plasmon Resonance

MeSH Major

  • Antibodies
  • Antigens, CD147
  • Integration Host Factors
  • Malaria
  • Plasmodium falciparum
  • Recombinant Fusion Proteins

abstract

  • Plasmodium falciparum is the parasite responsible for the most lethal form of malaria, an infectious disease that causes a large proportion of childhood deaths and poses a significant barrier to socioeconomic development in many countries. Although antimalarial drugs exist, the repeated emergence and spread of drug-resistant parasites limit their useful lifespan. An alternative strategy that could limit the evolution of drug-resistant parasites is to target host factors that are essential and universally required for parasite growth. Host-targeted therapeutics have been successfully applied in other infectious diseases but have never been attempted for malaria. Here, we report the development of a recombinant chimeric antibody (Ab-1) against basigin, an erythrocyte receptor necessary for parasite invasion as a putative antimalarial therapeutic. Ab-1 inhibited the PfRH5-basigin interaction and potently blocked erythrocyte invasion by all parasite strains tested. Importantly, Ab-1 rapidly cleared an established P. falciparum blood-stage infection with no overt toxicity in an in vivo infection model. Collectively, our data demonstrate that antibodies or other therapeutics targeting host basigin could be an effective treatment for patients infected with multi-drug resistant P. falciparum. © 2015 Zenonos et al.

publication date

  • July 27, 2015

has subject area

  • Animals
  • Antibodies
  • Antigens, CD147
  • Base Sequence
  • Carrier Proteins
  • Cloning, Molecular
  • Erythrocytes
  • Integration Host Factors
  • Malaria
  • Mice
  • Molecular Sequence Data
  • Plasmodium falciparum
  • Recombinant Fusion Proteins
  • Sequence Analysis, DNA
  • Surface Plasmon Resonance

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4516795

Digital Object Identifier (DOI)

  • 10.1084/jem.20150032

PubMed ID

  • 26195724

Additional Document Info

start page

  • 1145

end page

  • 1151

volume

  • 212

number

  • 8