Journal article
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
Actions
Authors
- 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
Terms of use
- Copyright holder:
- Alves et al
- Copyright date:
- 2017
- Notes:
- Copyright © 2017 Alves et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
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