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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.

Original publication

DOI

10.1016/j.chom.2014.11.017

Type

Journal article

Journal

Cell Host Microbe

Publication Date

14/01/2015

Volume

17

Pages

130 - 139

Keywords

Animals, Antibodies, Neutralizing, Antibodies, Protozoan, Antigens, Protozoan, Aotus trivirgatus, Carrier Proteins, Disease Models, Animal, Female, Immunity, Heterologous, Malaria, Malaria Vaccines, Neutralization Tests