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Evaluation of Plasmodium vivax Cell-Traversal Protein for Ookinetes and Sporozoites as a Preerythrocytic P. vivax Vaccine

Abstract:
Four different vaccine platforms each targeting the human malaria parasite Plasmodium vivax cell- traversal protein for ookinetes and sporozoites (PvCelTOS) were generated and assessed for protective efficacy. These platforms consisted of a recombinant chimpanzee adenoviral vector ChAd63-PvCelTOS (Ad); a recombinant MVA-PvCelTOS (MVA); a bacteriophage Qβ-PvCelTOS virus-like particle (VLP); and recombinant PvCelTOS protein expressed in eukaryotic HEK293T cells (protein). Inbred BALB/c and outbred CD-1 mice were immunized using the following prime/boost regimens: Ad-MVA, Ad-VLP and Ad-protein. Protective efficacy against sporozoite challenge was assessed after immunization using a novel chimeric rodent Plasmodium berghei parasite. This chimeric parasite (Pb-PvCelTOS) expresses P. vivax CelTOS in place of the endogenous P. berghei CelTOS and produces fully infectious sporozoites. A single A2 immunization in BALB/c and CD-1 mice induced anti-PvCelTOS antibodies which were boosted efficiently using MVA, VLP or protein immunization. High frequencies of PvCelTOS specific IFN-γ and TNF-α producing CD8+ 44 T-cells were induced by all prime/boost regimens in BALB/c but not in CD-1 mice; in CD1 mice they were only marginally increased after boosting with MVA. Despite the induction of anti-PvCelTOS antibodies and PvCelTOS-specific CD8+ 46 T-cell responses, only low protective efficacy against challenge with Pb-PvCelTOS sporozoites was obtained, using any immunization strategy. In BALB/c mice no immunization regimes provided significant protection against a Pb-PvCelTOS chimeric sporozoite challenge. In CD1 mice modest protective efficacy was observed using the Ad-Protein vaccination regimen against challenge with chimeric P. berghei sporozoites expressing either PvCelTOS or P. falciparum CelTOS.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1128/CVI.00501-16

Authors


More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Jenner Institute
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Jenner Institute
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Jenner Institute
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Jenner Institute
Role:
Author


Publisher:
American Society for Microbiology
Journal:
Clinical and Vaccine Immunology More from this journal
Volume:
24
Issue:
4
Pages:
e00501-16
Publication date:
2017-02-08
Acceptance date:
2017-01-31
DOI:
EISSN:
1556-679X
ISSN:
1556-6811


Pubs id:
pubs:675024
UUID:
uuid:194ff738-9e0e-4b3b-91c9-1b7d6dd55403
Local pid:
pubs:675024
Deposit date:
2017-01-31

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