title: A PfRH5-based vaccine is efficacious against heterologous strain blood-stage Plasmodium falciparum infection in aotus monkeys.
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.
authors.affiliation: Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK. Electronic address: sandy.douglas@ndm.ox.ac.uk.
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Douglas
authors.affiliation: US Naval Medical Research Unit No. 6 (NAMRU-6), Lima, Peru.
authors.forename: G Christian
authors.initials: GC
authors.lastname: Baldeviano
authors.affiliation: US Naval Medical Research Unit No. 6 (NAMRU-6), Lima, Peru.
authors.forename: Carmen M
authors.initials: CM
authors.lastname: Lucas
authors.affiliation: US Naval Medical Research Unit No. 6 (NAMRU-6), Lima, Peru.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Lugo-Roman
authors.affiliation: Wellcome Trust Sanger Institute, Cambridge CB10 1HH, UK.
authors.forename: Cécile
authors.initials: C
authors.lastname: Crosnier
authors.affiliation: Wellcome Trust Sanger Institute, Cambridge CB10 1HH, UK.
authors.forename: S Josefin
authors.initials: SJ
authors.lastname: Bartholdson
authors.affiliation: Laboratory of Malaria and Vector Research, NIAID/NIH, Rockville, MD 20852, USA.
authors.forename: Ababacar
authors.initials: A
authors.lastname: Diouf
authors.affiliation: Laboratory of Malaria and Vector Research, NIAID/NIH, Rockville, MD 20852, USA.
authors.forename: Kazutoyo
authors.initials: K
authors.lastname: Miura
authors.affiliation: Laboratory of Malaria Immunology and Vaccinology, NIAID/NIH, Rockville, MD 20852, USA.
authors.forename: Lynn E
authors.initials: LE
authors.lastname: Lambert
authors.affiliation: US Naval Medical Research Unit No. 6 (NAMRU-6), Lima, Peru.
authors.forename: Julio A
authors.initials: JA
authors.lastname: Ventocilla
authors.affiliation: US Naval Medical Research Unit No. 6 (NAMRU-6), Lima, Peru.
authors.forename: Karina P
authors.initials: KP
authors.lastname: Leiva
authors.affiliation: Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
authors.forename: Kathryn H
authors.initials: KH
authors.lastname: Milne
authors.affiliation: Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Illingworth
authors.affiliation: Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
authors.forename: Alexandra J
authors.initials: AJ
authors.lastname: Spencer
authors.affiliation: Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Hjerrild
authors.affiliation: Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
authors.forename: Daniel G W
authors.initials: DG
authors.lastname: Alanine
authors.affiliation: Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
authors.forename: Alison V
authors.initials: AV
authors.lastname: Turner
authors.affiliation: US Naval Medical Research Unit No. 6 (NAMRU-6), Lima, Peru.
authors.forename: Jeromy T
authors.initials: JT
authors.lastname: Moorhead
authors.affiliation: US Naval Medical Research Unit No. 6 (NAMRU-6), Lima, Peru.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Edgel
authors.affiliation: Laboratory of Malaria Immunology and Vaccinology, NIAID/NIH, Rockville, MD 20852, USA.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Laboratory of Malaria and Vector Research, NIAID/NIH, Rockville, MD 20852, USA.
authors.forename: Carole A
authors.initials: CA
authors.lastname: Long
authors.affiliation: Wellcome Trust Sanger Institute, Cambridge CB10 1HH, UK.
authors.forename: Gavin J
authors.initials: GJ
authors.lastname: Wright
authors.affiliation: US Naval Medical Research Unit No. 6 (NAMRU-6), Lima, Peru.
authors.forename: Andrés G
authors.initials: AG
authors.lastname: Lescano
authors.affiliation: Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Draper
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000276:immunology; D001029:Aotus trivirgatus; D002352:Carrier Proteins / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D064789:Immunity, Heterologous; D008288:Malaria / Q000276:immunology / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000276:immunology*; D009500:Neutralization Tests
chemical_list: D057134:Antibodies, Neutralizing; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D002352:Carrier Proteins; D017780:Malaria Vaccines; C531020:RH5 protein, Plasmodium falciparum