title: Protection againstPlasmodium falciparummalaria by PfSPZ Vaccine.
abstract: BACKGROUND: A radiation-attenuatedPlasmodium falciparum(Pf) sporozoite (SPZ) malaria vaccine, PfSPZ Vaccine, protected 6 of 6 subjects (100%) against homologous Pf (same strain as in the vaccine) controlled human malaria infection (CHMI) 3 weeks after 5 doses administered intravenously. The next step was to assess protective efficacy against heterologous Pf (different from Pf in the vaccine), after fewer doses, and at 24 weeks.METHODS: The trial assessed tolerability, safety, immunogenicity, and protective efficacy of direct venous inoculation (DVI) of 3 or 5 doses of PfSPZ Vaccine in non-immune subjects.RESULTS: Three weeks after final immunization, 5 doses of 2.7 × 105PfSPZ protected 12 of 13 recipients (92.3% [95% CI: 48.0, 99.8]) against homologous CHMI and 4 of 5 (80.0% [10.4, 99.5]) against heterologous CHMI; 3 doses of 4.5 × 105PfSPZ protected 13 of 15 (86.7% [35.9, 98.3]) against homologous CHMI. Twenty-four weeks after final immunization, the 5-dose regimen protected 7 of 10 (70.0% [17.3, 93.3]) against homologous and 1 of 10 (10.0% [-35.8, 45.6]) against heterologous CHMI; the 3-dose regimen protected 8 of 14 (57.1% [21.5, 76.6]) against homologous CHMI. All 22 controls developed Pf parasitemia. PfSPZ Vaccine was well tolerated, safe, and easy to administer. No antibody or T cell responses correlated with protection.CONCLUSIONS: We have demonstrated for the first time to our knowledge that PfSPZ Vaccine can protect against a 3-week heterologous CHMI in a limited group of malaria-naive adult subjects. A 3-dose regimen protected against both 3-week and 24-week homologous CHMI (87% and 57%, respectively) in this population. These results provide a foundation for developing an optimized immunization regimen for preventing malaria.TRIAL REGISTRATION: ClinicalTrials.gov NCT02215707.FUNDING: Support was provided through the US Army Medical Research and Development Command, Military Infectious Diseases Research Program, and the Naval Medical Research Center's Advanced Medical Development Program.
authors.affiliation: Naval Medical Research Center (NMRC).
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authors.lastname: Epstein
authors.affiliation: Walter Reed Army Institute of Research (WRAIR), Silver Spring, Maryland, USA.
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authors.affiliation: Sanaria Inc., Rockville, Maryland, USA.
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authors.affiliation: Naval Medical Research Center (NMRC).
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authors.affiliation: Naval Medical Research Center (NMRC).
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authors.affiliation: Sanaria Inc., Rockville, Maryland, USA.
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authors.affiliation: Sanaria Inc., Rockville, Maryland, USA.
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authors.affiliation: Walter Reed Army Institute of Research (WRAIR), Silver Spring, Maryland, USA.
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authors.affiliation: Walter Reed Army Institute of Research (WRAIR), Silver Spring, Maryland, USA.
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authors.affiliation: Sanaria Inc., Rockville, Maryland, USA.
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authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA.
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authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA.
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authors.affiliation: Walter Reed Army Institute of Research (WRAIR), Silver Spring, Maryland, USA.
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authors.affiliation: Walter Reed Army Institute of Research (WRAIR), Silver Spring, Maryland, USA.
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authors.affiliation: Walter Reed Army Institute of Research (WRAIR), Silver Spring, Maryland, USA.
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authors.affiliation: Naval Medical Research Center (NMRC).
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authors.affiliation: Sanaria Inc., Rockville, Maryland, USA.
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authors.affiliation: Walter Reed Army Institute of Research (WRAIR), Silver Spring, Maryland, USA.
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authors.affiliation: Walter Reed Army Institute of Research (WRAIR), Silver Spring, Maryland, USA.
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authors.affiliation: Sanaria Inc., Rockville, Maryland, USA.|Protein Potential, Rockville, Maryland, USA.
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mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D005260:Female; D006801:Humans; D016778:Malaria, Falciparum / Q000517:prevention & control / Q000628:therapy*; D008297:Male; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics; D034101:Sporozoites / Q000187:drug effects* / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology; D014613:Vaccines, Attenuated / Q000008:administration & dosage* / Q000627:therapeutic use; D000073336:Whole Genome Sequencing / Q000379:methods
chemical_list: D014613:Vaccines, Attenuated