@article{10.1172/jci.insight.89154, author = {Judith E. Epstein AND Kristopher M. Paolino AND Thomas L. Richie AND Martha Sedegah AND Alexandra Singer AND Adam J. Ruben AND Sumana Chakravarty AND April Stafford AND Richard C. Ruck AND Abraham G. Eappen AND Tao Li AND Peter F. Billingsley AND Anita Manoj AND Joana C. Silva AND Kara Moser AND Robin Nielsen AND Donna Tosh AND Susan Cicatelli AND Harini Ganeshan AND Jessica Case AND Debbie Padilla AND Silas Davidson AND Lindsey Garver AND Elizabeth Saverino AND Tooba Murshedkar AND Anusha Gunasekera AND Patrick S. Twomey AND Sharina Reyes AND James E. Moon AND Eric R. James AND Natasha KC AND Minglin Li AND Esteban Abot AND Arnel Belmonte AND Kevin Hauns AND Maria Belmonte AND Jun Huang AND Carlos Vasquez AND Shon Remich AND Mary Carrington AND Yonas Abebe AND Amy Tillman AND Bradley Hickey AND Jason Regules AND Eileen Villasante AND B. Kim Lee Sim AND Stephen L. Hoffman}, journal = {JCI Insight}, publisher = {The American Society for Clinical Investigation}, title = {Protection against Plasmodium falciparum malaria by PfSPZ Vaccine}, year = {2017}, month = {1}, volume = {2}, url = {https://insight.jci.org/articles/view/89154}, abstract = {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.}, number = {1}, doi = {10.1172/jci.insight.89154}, url = {https://doi.org/10.1172/jci.insight.89154}, }