A PfRH5-based Vaccine Is Efficacious Against Heterologous Strain Blood-Stage Plasmodium Falciparum Infection in Aotus Monkeys

Cell Host Microbe. 2015 Jan 14;17(1):130-9. doi: 10.1016/j.chom.2014.11.017.

Abstract

Antigenic diversity has posed a critical barrier to vaccine development against the pathogenic blood-stage infection of the human malaria parasite Plasmodium falciparum. To date, only strain-specific protection has been reported by trials of such vaccines in nonhuman primates. We recently showed that P. falciparum reticulocyte binding protein homolog 5 (PfRH5), a merozoite adhesin required for erythrocyte invasion, is highly susceptible to vaccine-inducible strain-transcending parasite-neutralizing antibody. In vivo efficacy of PfRH5-based vaccines has not previously been evaluated. Here, we demonstrate that PfRH5-based vaccines can protect Aotus monkeys against a virulent vaccine-heterologous P. falciparum challenge and show that such protection can be achieved by a human-compatible vaccine formulation. Protection was associated with anti-PfRH5 antibody concentration and in vitro parasite-neutralizing activity, supporting the use of this in vitro assay to predict the in vivo efficacy of future vaccine candidates. These data suggest that PfRH5-based vaccines have potential to achieve strain-transcending efficacy in humans.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Protozoan / blood
  • Antigens, Protozoan / immunology
  • Aotus trivirgatus
  • Carrier Proteins / immunology*
  • Disease Models, Animal
  • Female
  • Immunity, Heterologous*
  • Malaria / immunology
  • Malaria / prevention & control*
  • Malaria Vaccines / administration & dosage
  • Malaria Vaccines / immunology*
  • Neutralization Tests

Substances

  • Antibodies, Neutralizing
  • Antibodies, Protozoan
  • Antigens, Protozoan
  • Carrier Proteins
  • Malaria Vaccines
  • RH5 protein, Plasmodium falciparum