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

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 WuCarole A Long, Gavin J Wright, Andrés G Lescano, Simon J Draper

Research output: Contribution to journalArticlepeer-review

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

Keywords

  • first & last 3 (QQ only)

Cite this