Protection against Plasmodium falciparum malaria by PfSPZ Vaccine.

BACKGROUND: A radiation-attenuated Plasmodium 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 × 105 PfSPZ 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 × 105 PfSPZ 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.

Sumana Chakravarty | Joana C. Silva | S. Hoffman | Elizabeth Saverino | P. Billingsley | T. Richie | B. Sim | L. Garver | J. Moon | K. Paolino | M. Sedegah | A. Eappen | S. Chakravarty | E. Abot | H. Ganeshan | M. Belmonte | Jun Huang | Eileen D. Villasante | J. Epstein | A. Gunasekera | E. James | S. Reyes | A. Ruben | Anita Manoj | Minglin Li | Tao Li | S. Davidson | Tooba Murshedkar | Natasha Kc | Y. Abebe | J. Regules | Thomas L Richie | Elizabeth Saverino | Tao Li | Anusha Gunasekera | Minglin Li | Martha Sedegah | Sharina Reyes | A. Belmonte | K. Moser | Shon A. Remich | Tooba Murshedkar | Adam J Ruben | Yonas Abebe | Anita Manoj | B Kim Lee Sim | Peter F Billingsley | Eric R James | Stephen L Hoffman | Abraham G Eappen | Debbie Padilla | Joana C Silva | Robin Nielsen | Natasha Kc | Judith E Epstein | Kristopher M Paolino | Alexandra Singer | April Stafford | Richard C Ruck | Kara Moser | Donna Tosh | Susan Cicatelli | Harini Ganeshan | Jessica Case | Silas Davidson | Lindsey Garver | Patrick S Twomey | James E Moon | Esteban Abot | Arnel Belmonte | Kevin Hauns | Maria Belmonte | Jun Huang | Carlos Vasquez | Shon Remich | Mary Carrington | Amy Tillman | Bradley Hickey | Jason Regules | Eileen Villasante | M. Carrington | Kevin Hauns | Donna M Tosh | Amy Tillman | Jessica Case | P. Twomey | Richard C. Ruck | Bradley W. Hickey | Alexandra Singer | C. Vásquez | R. Nielsen | Susan B Cicatelli | Debbie Padilla | April Stafford | Stephen L. Hoffman | Eric R. James | Harini Ganeshan | Mary Carrington | S. Cicatelli

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