Evaluation of Plasmodium vivax Cell-Traversal Protein for Ookinetes and Sporozoites as a Preerythrocytic P. vivax Vaccine
- Alves, Eduardo The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
- Salman, Ahmed M. Leiden Malaria Research Group, Department of Parasitology, Center of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands
- Leoratti, Fabiana Immunology, RIA, Inselspital, University of Bern, Bern, Switzerland
- Lopez-Camacho, Cesar The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
- Viveros-Sandoval, Martha Eva Laboratorio de Hemostasia y Biología Vascular, División de Estudios de Posgrado, Facultad de Ciencias Médicas y Biológicas Dr. Ignacio Chávez, Universidad Michoacana de San Nicolás de Hidalgo, Morelia, Michoacán, Mexico
- Lall, Amar The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
- El-Turabi, Aadil The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
- Bachmann, Martin F. Immunology, RIA, Inselspital, University of Bern, Bern, Switzerland
- Hill, Adrian V. S. The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
- Janse, Chris J. Leiden Malaria Research Group, Department of Parasitology, Center of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands
- Khan, Shahid M. Leiden Malaria Research Group, Department of Parasitology, Center of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands
- Reyes-Sandoval, Arturo The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
- 2017-4-5
Published in:
- Clinical and Vaccine Immunology. - American Society for Microbiology. - 2017, vol. 24, no. 4
English
ABSTRACT
Four different vaccine platforms, each targeting the human malaria parasite Plasmodium vivax cell-traversal protein for ookinetes and sporozoites (Pv CelTOS), were generated and assessed for protective efficacy. These platforms consisted of a recombinant chimpanzee adenoviral vector 63 (ChAd63) expressing Pv CelTOS (Ad), a recombinant modified vaccinia virus Ankara expressing Pv CelTOS (MVA), Pv CelTOS conjugated to bacteriophage Qβ virus-like particles (VLPs), and a recombinant Pv CelTOS protein expressed in eukaryotic HEK293T cells (protein). Inbred BALB/c mice and outbred CD-1 mice were immunized using the following prime-boost regimens: Ad-MVA, Ad-VLPs, and Ad-protein. Protective efficacy against sporozoite challenge was assessed after immunization using a novel chimeric rodent Plasmodium berghei parasite (Pb-Pv CelTOS). This chimeric parasite expresses P. vivax CelTOS in place of the endogenous P. berghei CelTOS and produces fully infectious sporozoites. A single Ad immunization in BALB/c and CD-1 mice induced anti-Pv CelTOS antibodies which were boosted efficiently using MVA, VLP, or protein immunization. Pv CelTOS-specific gamma interferon- and tumor necrosis factor alpha-producing CD8+ T cells were induced at high frequencies by all prime-boost regimens in BALB/c mice but not in CD-1 mice; in CD-1 mice, they were only marginally increased after boosting with MVA. Despite the induction of anti-Pv CelTOS antibodies and Pv CelTOS-specific CD8+ T-cell responses, only low levels of protective efficacy against challenge with Pb-Pv CelTOS sporozoites were obtained using any immunization strategy. In BALB/c mice, no immunization regimens provided significant protection against a Pb-Pv CelTOS chimeric sporozoite challenge. In CD-1 mice, modest protective efficacy against challenge with chimeric P. berghei sporozoites expressing either Pv CelTOS or P. falciparum CelTOS was observed using the Ad-protein vaccination regimen.
- Language
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- English
- Open access status
- gold
- Identifiers
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- DOI 10.1128/cvi.00501-16
- ISSN 1556-6811
- Persistent URL
- https://sonar.ch/global/documents/82074
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