The Plasmodium falciparum Cell-Traversal Protein for Ookinetes and Sporozoites as a Candidate for Preerythrocytic and Transmission-Blocking Vaccines

Espinosa, Diego A.; Vega-Rodríguez, Joel; Flores-García, Yevel; Noe, Amy R.; Muñoz, Christian; Coleman, Russell E.; Bruck, Torben; Haney, Keith; Stevens, Alex; Retallack, Diane M.; Allen, Jeff; Vedvick, Thomas S.; Fox, Christopher B.; Reed, Steven G.; Howard, Randall F.; Salman, Ahmed M.; Janse, Chris J.; Khan, Shahid M.; Zavala, Fidel; Gutierrez, Gabriel M.

doi:10.1128/iai.00498-16

Cited by 58 publications

(48 citation statements)

References 35 publications

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“…falciparum CelTOS (Fig. 4A to D) (29, 30). Protective efficacy was determined by measuring the prepatent period after sporozoite challenge.…”

Section: Resultsmentioning

confidence: 99%

“…All mice were challenged 66 days after the boost either with wild-type (WT) P. berghei sporozoites or with chimeric sporozoites expressing Pv CelTOS or Pf CelTOS (29). (A) Protective efficacy after challenge of immunized CD-1 mice with 1,000 sporozoites of the chimeric parasite line expressing P.…”

Section: Resultsmentioning

confidence: 99%

“…(C) Protective efficacy after challenge of immunized CD-1 mice with 1,000 sporozoites of the chimeric parasite line expressing P. falciparum CelTOS (29). Protective efficacy was significantly higher for mice immunized with Ad-protein ( P = 0.0488) than for the naive group (log-rank Mantel-Cox test for comparison of survival curves).…”

Section: Resultsmentioning

confidence: 99%

“…berghei parasite and a chimeric parasite expressing P. falciparum CelTOS recently described in the literature (29, 30). …”

Section: Introductionmentioning

confidence: 99%

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

Alves

Salman

Leoratti

et al. 2017

Clin Vaccine Immunol

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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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“…falciparum CelTOS (Fig. 4A to D) (29, 30). Protective efficacy was determined by measuring the prepatent period after sporozoite challenge.…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

“…berghei parasite and a chimeric parasite expressing P. falciparum CelTOS recently described in the literature (29, 30). …”

Section: Introductionmentioning

confidence: 99%

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

Alves

Salman

Leoratti

et al. 2017

Clin Vaccine Immunol

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“…The chimeric parasites used in this study had the HMP gene introduced as an additional gene copy as a number of the selected genes did not have an ortholog in the P. berghei genome, thereby excluding the possibility to make replacement mutants. A number of other chimeric RMP have been used, which express a HMP ortholog in place of their own RMP gene (Table 1), for example chimeric parasites expressing preerythrocytic vaccine candidates such as P. vivax and P. falciparum CSP and CelTOS ( [34,39,41,85]; Table 1). …”

Section: Chimeric Rodent Parasites Expressing Human Plasmodium Proteinsmentioning

confidence: 99%

The use of transgenic parasites in malaria vaccine research

Othman

Marin-Mogollon

Salman

et al. 2017

Expert Review of Vaccines

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Introduction: Transgenic malaria parasites expressing foreign genes, for example fluorescent and luminescent proteins, are used extensively to interrogate parasite biology and host-parasite interactions associated with malaria pathology. Increasingly transgenic parasites are also exploited to advance malaria vaccine development. Areas covered: We review how transgenic malaria parasites are used, in vitro and in vivo, to determine protective efficacy of different antigens and vaccination strategies and to determine immunological correlates of protection. We describe how chimeric rodent parasites expressing P. falciparum or P. vivax antigens are being used to directly evaluate and rank order human malaria vaccines before their advancement to clinical testing. In addition, we describe how transgenic human and rodent parasites are used to develop and evaluate live (genetically) attenuated vaccines. Expert commentary: Transgenic rodent and human malaria parasites are being used to both identify vaccine candidate antigens and to evaluate both sub-unit and whole organism vaccines before they are advanced into clinical testing. Transgenic parasites combined with in vivo pre-clinical testing models (e.g. mice) are used to evaluate vaccine safety, potency and the durability of protection as well as to uncover critical protective immune responses and to refine vaccination strategies. ARTICLE HISTORY

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Toll‐Like Receptor‐Based Adjuvants: A Gateway Toward Improved Malaria Vaccination

Kannan¹,

Kaur²,

Salunke³

et al. 2022

Drug Development for Malaria

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The Plasmodium falciparum Cell-Traversal Protein for Ookinetes and Sporozoites as a Candidate for Preerythrocytic and Transmission-Blocking Vaccines

Cited by 58 publications

References 35 publications

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

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

The use of transgenic parasites in malaria vaccine research

Toll‐Like Receptor‐Based Adjuvants: A Gateway Toward Improved Malaria Vaccination

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