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

TY - JOUR

T1 - A PfRH5-based vaccine is efficacious against heterologous strain blood-stage Plasmodium falciparum infection in aotus monkeys

AU - Douglas, Alexander D

AU - Baldeviano, G Christian

AU - Lucas, Carmen M

AU - Lugo-Roman, Luis A

AU - Crosnier, Cécile

AU - Bartholdson, S Josefin

AU - Diouf, Ababacar

AU - Miura, Kazutoyo

AU - Lambert, Lynn E

AU - Ventocilla, Julio A

AU - Leiva, Karina P

AU - Milne, Kathryn H

AU - Illingworth, Joseph J

AU - Spencer, Alexandra J

AU - Hjerrild, Kathryn A

AU - Alanine, Daniel G W

AU - Turner, Alison V

AU - Moorhead, Jeromy T

AU - Edgel, Kimberly A

AU - Wu, Yimin

AU - Long, Carole A

AU - Wright, Gavin J

AU - Lescano, Andrés G

AU - Draper, Simon J

PY - 2015/1/14

Y1 - 2015/1/14

N2 - 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.

AB - 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.

KW - first & last 3 (QQ only)

U2 - 10.1016/j.chom.2014.11.017

DO - 10.1016/j.chom.2014.11.017

M3 - Article

SN - 1931-3128

VL - 17

SP - 130

EP - 139

JO - Cell Host & Microbe

JF - Cell Host & Microbe

IS - 1

ER -