Title
A PfRH5-based vaccine is efficacious against heterologous strain blood-stage plasmodium falciparum infection in Aotus monkeys
Date Issued
14 January 2015
Access level
open access
Resource Type
journal article
Author(s)
Douglas A.D.
Lugo-Roman L.A.
Crosnier C.
Bartholdson S.J.
Diouf A.
Miura K.
Lambert L.E.
Leiva K.P.
Milne K.H.
Illingworth J.J.
Spencer A.J.
Hjerrild K.A.
Alanine D.G.W.
Turner A.V.
Moorhead J.T.
Edgel K.A.
Wu Y.
Long C.A.
Wright G.J.
Draper S.J.
Unidad de Investigación Médica Naval-6
Unidad de Investigación Médica Naval-6
Unidad de Investigación Médica Naval-6
Unidad de Investigación Médica Naval-6
Publisher(s)
Cell Press
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.
Start page
130
End page
139
Volume
17
Issue
1
Language
English
OCDE Knowledge area
Enfermedades infecciosas
Ciencia veterinaria
Scopus EID
2-s2.0-84920932154
PubMed ID
Source
Cell Host and Microbe
ISSN of the container
19313128
Sponsor(s)
The authors are grateful for the assistance of Adrian Hill, Julie Furze, the Viral Vector Core Facility and Adjuvant Bank (Jenner Institute, University of Oxford); David Staunton (Biophysical Instrument Facility, Department of Biochemistry, University of Oxford); Ly-Mee Yu and Doug Altman (Centre for Statistics in Medicine, University of Oxford); Julian Rayner (Wellcome Trust Sanger Institute, UK); Carmen Franco, Roxana Lescano, Jorge Nuñez, Meddly Santolalla, and Lorena Tapia (NAMRU-6, Peru); Olivo Miotto (Mahidol-Oxford Research Unit, Thailand); Yves Durocher for provision of HEK293E cells (CNRC-NRC, Canada); and Alfredo Nicosia (Okairòs, Italy) for provision of the ChAd63 vector. A.D.D. held a Wellcome Trust Training Fellowship for Clinicians in Basic Sciences (grant number 089455/2/09/z). J.J.I. is a Wellcome Trust funded student on the Infection, Immunology and Translational Medicine PhD Programme (grant number 092873/z/10/z). C.C., S.J.B., and G.J.W. are supported by the Wellcome Trust (grant number 098051). The GIA work was supported by the PATH Malaria Vaccine Initiative and the Intramural Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases. This work was also funded in part by the University Challenge Seed Fund (Isis Innovation, University of Oxford) and by the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement number 242095 – EVIMalaR. A.G.L. is supported by training grant NIH/FIC 2D43 TW007393 awarded to NAMRU-6 by the Fogarty International Center of the US National Institutes of Health. S.J.D. holds a MRC Career Development Fellowship (grant number G1000527; this fellowship is jointly funded by the UK Medical Research Council [MRC] and the UK Department for International Development [DFID] under the MRC/DFID Concordat agreement) and is a Jenner Investigator and Lister Institute Research Prize Fellow. A.D.D., J.J.I., C.C., S.J.B., G.J.W., and S.J.D. are named on patent applications relating to PfRH5 and/or other malaria vaccines. Some of the listed authors are either military service members (K.A.E., L.A.L.-R., J.T.M.) or employees of the US Government (G.C.B., C.M.L., J.A.V., K.P.L., A.G.L.). This work was prepared as part of their official duties. Title 17 U.S.C. §105 provides that “Copyright protection under this title is not available for any work of the United States Government.” Title 17 U.S.C. §101 defines a U.S. Government work as a work prepared by a military service member or employee of the US Government as part of that person’s official duties. The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, or the US Government.
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