TY - JOUR AU - Epstein, Judith E. AU - Paolino, Kristopher M. AU - Richie, Thomas L. AU - Sedegah, Martha AU - Singer, Alexandra AU - Ruben, Adam J. AU - Chakravarty, Sumana AU - Stafford, April AU - Ruck, Richard C. AU - Eappen, Abraham G. AU - Li, Tao AU - Billingsley, Peter F. AU - Manoj, Anita AU - Silva, Joana C. AU - Moser, Kara AU - Nielsen, Robin AU - Tosh, Donna AU - Cicatelli, Susan AU - Ganeshan, Harini AU - Case, Jessica AU - Padilla, Debbie AU - Davidson, Silas AU - Garver, Lindsey AU - Saverino, Elizabeth AU - Murshedkar, Tooba AU - Gunasekera, Anusha AU - Twomey, Patrick S. AU - Reyes, Sharina AU - Moon, James E. AU - James, Eric R. AU - KC, Natasha AU - Li, Minglin AU - Abot, Esteban AU - Belmonte, Arnel AU - Hauns, Kevin AU - Belmonte, Maria AU - Huang, Jun AU - Vasquez, Carlos AU - Remich, Shon AU - Carrington, Mary AU - Abebe, Yonas AU - Tillman, Amy AU - Hickey, Bradley AU - Regules, Jason AU - Villasante, Eileen AU - Sim, B. Kim Lee AU - Hoffman, Stephen L. T1 - Protection against Plasmodium falciparum malaria by PfSPZ Vaccine PY - 2017/01/12/ AB - 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. JF - JCI Insight JA - JCI Insight SN - 2379-3708 DO - 10.1172/jci.insight.89154 VL - 2 IS - 1 UR - https://doi.org/10.1172/jci.insight.89154 PB - The American Society for Clinical Investigation ER -