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

Abstract

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.