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<jats:title>ABSTRACT</jats:title> <jats:p>Four different vaccine platforms, each targeting the human malaria parasite <jats:named-content content-type="genus-species">Plasmodium vivax</jats:named-content> cell-traversal protein for ookinetes and sporozoites (<jats:italic>Pv</jats:italic>CelTOS), were generated and assessed for protective efficacy. These platforms consisted of a recombinant chimpanzee adenoviral vector 63 (ChAd63) expressing <jats:italic>Pv</jats:italic>CelTOS (Ad), a recombinant modified vaccinia virus Ankara expressing <jats:italic>Pv</jats:italic>CelTOS (MVA), <jats:italic>Pv</jats:italic>CelTOS conjugated to bacteriophage Qβ virus-like particles (VLPs), and a recombinant <jats:italic>Pv</jats:italic>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 <jats:named-content content-type="genus-species">Plasmodium berghei</jats:named-content> parasite (<jats:italic>Pb-Pv</jats:italic>CelTOS). This chimeric parasite expresses <jats:named-content content-type="genus-species">P. vivax</jats:named-content> CelTOS in place of the endogenous <jats:named-content content-type="genus-species">P. berghei</jats:named-content> CelTOS and produces fully infectious sporozoites. A single Ad immunization in BALB/c and CD-1 mice induced anti-<jats:italic>Pv</jats:italic>CelTOS antibodies which were boosted efficiently using MVA, VLP, or protein immunization. <jats:italic>Pv</jats:italic>CelTOS-specific gamma interferon- and tumor necrosis factor alpha-producing CD8<jats:sup>+</jats:sup> 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-<jats:italic>Pv</jats:italic>CelTOS antibodies and <jats:italic>Pv</jats:italic>CelTOS-specific CD8<jats:sup>+</jats:sup> T-cell responses, only low levels of protective efficacy against challenge with <jats:italic>Pb-Pv</jats:italic>CelTOS sporozoites were obtained using any immunization strategy. In BALB/c mice, no immunization regimens provided significant protection against a <jats:italic>Pb-Pv</jats:italic>CelTOS chimeric sporozoite challenge. In CD-1 mice, modest protective efficacy against challenge with chimeric <jats:named-content content-type="genus-species">P. berghei</jats:named-content> sporozoites expressing either <jats:italic>Pv</jats:italic>CelTOS or <jats:named-content content-type="genus-species">P. falciparum</jats:named-content> CelTOS was observed using the Ad-protein vaccination regimen.</jats:p>

Original publication

DOI

10.1128/cvi.00501-16

Type

Journal article

Journal

Clinical and Vaccine Immunology

Publisher

American Society for Microbiology

Publication Date

04/2017

Volume

24