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

Alves, Eduardo; Salman, Ahmed M.; Leoratti, Fabiana; Lopez-Camacho, Cesar; Viveros-Sandoval, Martha Eva; Lall, Amar; El-Turabi, Aadil; Bachmann, Martin F.; Hill, Adrian V. S.; Janse, Chris J.; Khan, Shahid M.; Reyes-Sandoval, Arturo

doi:10.1128/cvi.00501-16

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Journal article

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 (PvCelTOS), were generated and assessed for protective efficacy. These platforms consisted of a recombinant chimpanzee adenoviral vector 63 (ChAd63) expressing PvCelTOS (Ad), a recombinant modified vaccinia virus Ankara expressing PvCelTOS (MVA), PvCelTOS conjugated to bacteriophage Qβ virus-like particles (VLPs), and a recombinant PvCelTOS 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-PvCelTOS). 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-PvCelTOS antibodies which were boosted efficiently using MVA, VLP, or protein immunization. PvCelTOS-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-PvCelTOS antibodies and PvCelTOS-specific CD8+ T-cell responses, only low levels of protective efficacy against challenge with Pb-PvCelTOS sporozoites were obtained using any immunization strategy. In BALB/c mice, no immunization regimens provided significant protection against a Pb-PvCelTOS chimeric sporozoite challenge. In CD-1 mice, modest protective efficacy against challenge with chimeric P. berghei sporozoites expressing either PvCelTOS or P. falciparum CelTOS was observed using the Ad-protein vaccination regimen.

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