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A PfRH5-based vaccine is efficacious against heterologous strain blood-stage Plasmodium falciparum infection in aotus monkeys

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Author(s)

  • Alexander D Douglas
  • G Christian Baldeviano
  • Carmen M Lucas
  • Luis A Lugo-Roman
  • Cécile Crosnier
  • S Josefin Bartholdson
  • Ababacar Diouf
  • Kazutoyo Miura
  • Lynn E Lambert
  • Julio A Ventocilla
  • Karina P Leiva
  • Kathryn H Milne
  • Joseph J Illingworth
  • Alexandra J Spencer
  • Kathryn A Hjerrild
  • Daniel G W Alanine
  • Alison V Turner
  • Jeromy T Moorhead
  • Kimberly A Edgel
  • Yimin Wu
  • Carole A Long
  • Andrés G Lescano
  • Simon J Draper

Department/unit(s)

Publication details

JournalCell Host & Microbe
DatePublished - 14 Jan 2015
Issue number1
Volume17
Number of pages10
Pages (from-to)130-139
Original languageEnglish

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. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

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