Evaluation of Plasmodium vivax Cell-Traversal Protein for Ookinetes and Sporozoites as a Preerythrocytic P. vivax Vaccine.
Four different vaccine platforms, each targeting the human malaria parasitePlasmodium vivaxcell-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) expressingPvCelTOS (Ad), a recombinant modified vaccinia virus Ankara expressingPvCelTOS (MVA),PvCelTOS conjugated to bacteriophage Qβ virus-like particles (VLPs), and a recombinantPvCelTOS 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 rodentPlasmodium bergheiparasite (Pb-PvCelTOS). This chimeric parasite expressesP. vivaxCelTOS in place of the endogenousP. bergheiCelTOS 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 andPvCelTOS-specific CD8+T-cell responses, only low levels of protective efficacy against challenge withPb-PvCelTOS sporozoites were obtained using any immunization strategy. In BALB/c mice, no immunization regimens provided significant protection against aPb-PvCelTOS chimeric sporozoite challenge. In CD-1 mice, modest protective efficacy against challenge with chimericP. bergheisporozoites expressing eitherPvCelTOS orP. falciparumCelTOS was observed using the Ad-protein vaccination regimen.
The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
Eduardo
E
Alves
The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.|Leiden Malaria Research Group, Department of Parasitology, Center of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
Ahmed M
AM
Salman
The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.|Immunology, RIA, Inselspital, University of Bern, Bern, Switzerland.
Fabiana
F
Leoratti
The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
Cesar
C
Lopez-Camacho
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.
Martha Eva
ME
Viveros-Sandoval
The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
Amar
A
Lall
The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
Aadil
A
El-Turabi
The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.|Immunology, RIA, Inselspital, University of Bern, Bern, Switzerland.
Martin F
MF
Bachmann
The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
Adrian V S
AV
Hill
Leiden Malaria Research Group, Department of Parasitology, Center of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
Chris J
CJ
Janse
Leiden Malaria Research Group, Department of Parasitology, Center of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
Shahid M
SM
Khan
The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom arturo.reyes@ndm.ox.ac.uk.
Arturo
A
Reyes-Sandoval
D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000008:administration & dosage / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D004337:Drug Carriers; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016780:Malaria, Vivax / Q000517:prevention & control*; D051379:Mice; D010966:Plasmodium vivax / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D004337:Drug Carriers; D017780:Malaria Vaccines; D014409:Tumor Necrosis Factor-alpha; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; D007371:Interferon-gamma
CelTOS; Plasmodium; malaria; preerythrocytic; vaccine; vivax