Preclinical assessment of the receptor-binding domain of Plasmodium vivax Duffy-binding protein as a vaccine candidate in rhesus macaques

Abstract The receptor-binding domain of Plasmodium vivax Duffy-binding protein, region II (PvRII), is an attractive candidate for a vaccine against P. vivax malaria. Here, we have studied the safety and immunogenicity of recombinant PvRII in Macaca mulatta (rhesus monkeys). Recombinant PvRII with a...

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Veröffentlicht in:Vaccine 2008-08, Vol.26 (34), p.4338-4344
Hauptverfasser: Moreno, A, Caro-Aguilar, I, Yazdani, S.S, Shakri, A.R, Lapp, S, Strobert, E, McClure, H, Chitnis, C.E, Galinski, M.R
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container_end_page 4344
container_issue 34
container_start_page 4338
container_title Vaccine
container_volume 26
creator Moreno, A
Caro-Aguilar, I
Yazdani, S.S
Shakri, A.R
Lapp, S
Strobert, E
McClure, H
Chitnis, C.E
Galinski, M.R
description Abstract The receptor-binding domain of Plasmodium vivax Duffy-binding protein, region II (PvRII), is an attractive candidate for a vaccine against P. vivax malaria. Here, we have studied the safety and immunogenicity of recombinant PvRII in Macaca mulatta (rhesus monkeys). Recombinant PvRII with a C-terminal 6-histidine tag was expressed in E. coli , recovered from inclusion bodies, refolded into its functional conformation, purified to homogeneity and formulated with three adjuvants, namely, Alhydrogel, Montanide ISA 720 and the GSK proprietary Adjuvant System AS02A for use in immunogenicity studies. All the PvRII vaccine formulations tested were safe and highly immunogenic. The overall magnitude of the antibody response was significantly higher for both Montanide ISA 720 and AS02A formulations in comparison with Alhydrogel. Furthermore, there was a significant correlation between antibody recognition titers by ELISA and binding inhibition titers in in vitro binding assays. The PvRII vaccine formulations also induced IFN-γ recall responses that were identified using ex vivo ELISPOT assays. These results provide support for further clinical development of a vaccine for P. vivax malaria based on recombinant PvRII.
doi_str_mv 10.1016/j.vaccine.2008.06.010
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language eng
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subjects Adjuvant formulation
Adjuvants, Immunologic - administration & dosage
Allergy and Immunology
Aluminum Hydroxide - administration & dosage
Animals
Antibodies, Protozoan - blood
Antigens, Protozoan - immunology
Applied microbiology
Biological and medical sciences
Duffy-binding protein
Enzyme-Linked Immunosorbent Assay
Escherichia coli
Fundamental and applied biological sciences. Psychology
Human protozoal diseases
Infectious diseases
Interferon-gamma - secretion
Lymphocytes - immunology
Macaca mulatta
Malaria
Malaria - prevention & control
Malaria - veterinary
Malaria vaccine
Malaria Vaccines - immunology
Mannitol - administration & dosage
Mannitol - analogs & derivatives
Medical sciences
Microbiology
Oleic Acids - administration & dosage
Parasitic diseases
Plasmodium vivax
Protein Binding
Protozoal diseases
Protozoan Proteins - immunology
Receptors, Cell Surface - immunology
Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects)
Vaccines, Synthetic - immunology
title Preclinical assessment of the receptor-binding domain of Plasmodium vivax Duffy-binding protein as a vaccine candidate in rhesus macaques
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