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

Autor: Douglas AD; Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK. Electronic address: sandy.douglas@ndm.ox.ac.uk., Baldeviano GC; US Naval Medical Research Unit No. 6 (NAMRU-6), Lima, Peru., Lucas CM; US Naval Medical Research Unit No. 6 (NAMRU-6), Lima, Peru., Lugo-Roman LA; US Naval Medical Research Unit No. 6 (NAMRU-6), Lima, Peru., Crosnier C; Wellcome Trust Sanger Institute, Cambridge CB10 1HH, UK., Bartholdson SJ; Wellcome Trust Sanger Institute, Cambridge CB10 1HH, UK., Diouf A; Laboratory of Malaria and Vector Research, NIAID/NIH, Rockville, MD 20852, USA., Miura K; Laboratory of Malaria and Vector Research, NIAID/NIH, Rockville, MD 20852, USA., Lambert LE; Laboratory of Malaria Immunology and Vaccinology, NIAID/NIH, Rockville, MD 20852, USA., Ventocilla JA; US Naval Medical Research Unit No. 6 (NAMRU-6), Lima, Peru., Leiva KP; US Naval Medical Research Unit No. 6 (NAMRU-6), Lima, Peru., Milne KH; Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK., Illingworth JJ; Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK., Spencer AJ; Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK., Hjerrild KA; Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK., Alanine DG; Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK., Turner AV; Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK., Moorhead JT; US Naval Medical Research Unit No. 6 (NAMRU-6), Lima, Peru., Edgel KA; US Naval Medical Research Unit No. 6 (NAMRU-6), Lima, Peru., Wu Y; Laboratory of Malaria Immunology and Vaccinology, NIAID/NIH, Rockville, MD 20852, USA., Long CA; Laboratory of Malaria and Vector Research, NIAID/NIH, Rockville, MD 20852, USA., Wright GJ; Wellcome Trust Sanger Institute, Cambridge CB10 1HH, UK., Lescano AG; US Naval Medical Research Unit No. 6 (NAMRU-6), Lima, Peru., Draper SJ; Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
Jazyk: angličtina
Zdroj: Cell host & microbe [Cell Host Microbe] 2015 Jan 14; Vol. 17 (1), pp. 130-9.
DOI: 10.1016/j.chom.2014.11.017
Abstrakt: 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.)
Databáze: MEDLINE