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Title: Preclinical assessment of viral vectored and protein vaccines targeting the Duffy-binding protein region II of Plasmodium vivax
Authors: de Cassan S.C.
Rushdi Shakri A.
Llewellyn D.
Elias S.C.
Cho J.S.
Goodman A.L.
Jin J.
Douglas A.D.
Suwanarusk R.
Nosten F.H.
Rénia L. 
Russell B. 
Chitnis C.E.
Draper S.J.
Keywords: Duffy binding protein
gamma interferon
malaria vaccine
plasmodium vivax duffy binding protein region 2 vaccine
thymidine kinase
tissue plasminogen activator
unclassified drug
virus vector
animal model
animal tissue
antibody response
cell invasion
chimpanzee adenovirus serotype 63
controlled study
DNA virus
drug targeting
enzyme inhibition assay
enzyme linked immunosorbent assay
gel permeation chromatography
gene expression
Human adenovirus 5
immobilized metal affinity chromatography
immunofluorescence test
nucleotide sequence
Plasmodium vivax malaria
protein binding
recombinant DNA technology
recurrent disease
ultraviolet spectrophotometry
Issue Date: 2015
Citation: de Cassan S.C., Rushdi Shakri A., Llewellyn D., Elias S.C., Cho J.S., Goodman A.L., Jin J., Douglas A.D., Suwanarusk R., Nosten F.H., Rénia L., Russell B., Chitnis C.E., Draper S.J. (2015). Preclinical assessment of viral vectored and protein vaccines targeting the Duffy-binding protein region II of Plasmodium vivax. Frontiers in Immunology 6 (JUN) : 348. ScholarBank@NUS Repository.
Abstract: Malaria vaccine development has largely focused on Plasmodium falciparum; however a reawakening to the importance of P. vivax has spurred efforts to develop vaccines against this difficult to treat and at times severe form of relapsing malaria, which constitutes a significant proportion of human malaria cases worldwide. The almost complete dependence of P. vivax red blood cell invasion on the interaction of the P. vivax Duffy-binding protein region II (PvDBP_RII) with the human Duffy antigen receptor for chemokines (DARC), makes this antigen an attractive vaccine candidate against blood-stage P. vivax. Here, we generated both preclinical and clinically-compatible adenoviral and poxviral vectored vaccine candidates expressing the Salvador I allele of PvDBP_RII -including human adenovirus serotype 5 (HAdV5), chimpanzee adenovirus serotype 63 (ChAd63) and modified vaccinia virus Ankara (MVA) vectors. We report on the antibody and T cell immunogenicity of these vaccines in mice or rabbits, either used alone in a viral vectored prime-boost regime, or in 'mixed modality' adenovirus prime -protein-in-adjuvant boost regimes (using a recombinant protein PvDBP_RII protein antigen formulated in Montanide®ISA720 or Abisco®100 adjuvants). Antibodies induced by these regimes were found to bind to native parasite antigen from P. vivax infected Thai patients and were capable of inhibiting the binding of PvDBP_RII to its receptor DARC using an in vitro binding inhibition assay. In recent years, recombinant ChAd63 and MVA vectors have been quickly translated into human clinical trials for numerous antigens from P. falciparum as well as a growing number of other pathogens. The vectors reported here are immunogenic in small animals, elicit antibodies against PvDBP_RII and have recently entered clinical trials which will provide the first assessment of the safety and immunogenicity of the PvDBP_RII antigen in humans. © 2015 De_cassan, Shakri, Llewellyn, Elias, Cho, Goodman, Jin, Douglas, Suwanarusk, Nosten, Rénia, Russell, Chitnis and Draper.
Source Title: Frontiers in Immunology
ISSN: 16643224
DOI: 10.3389/fimmu.2015.00348
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