期刊
CELL HOST & MICROBE
卷 17, 期 1, 页码 130-139出版社
CELL PRESS
DOI: 10.1016/j.chom.2014.11.017
关键词
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资金
- Wellcome Trust [089455/2/09/z, 092873/z/10/z, 098051]
- PATH Malaria Vaccine Initiative
- Intramural Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases
- University Challenge Seed Fund (Isis Innovation, University of Oxford)
- European Community's Seventh Framework Programme (FP7) [242095 - EVIMalaR]
- NIH/FIC by the Fogarty International Center of the US National Institutes of Health [2D43 TW007393]
- MRC Career Development Fellowship - UK Medical Research Council [MRC] [G1000527]
- MRC Career Development Fellowship - UK Department for International Development [DFID] [G1000527]
- Wellcome Trust [092873/Z/10/Z] Funding Source: Wellcome Trust
- Medical Research Council [G1000527, 1369217] Funding Source: researchfish
- MRC [G1000527] Funding Source: UKRI
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.
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