USSPZV6 is a single site, double-blind, randomized, placebo-controlled, clinical trial. Study groups will be randomized in a 14:4 ratio (vaccine to NS placebo) among healthy, malaria-naive adults aged 18-50 years. There will be three groups of subjects. Each of the 3 groups will have 14 subjects who receive 3 injections with 9 x 10\^5 PfSPZ of PfSPZ Vaccine and 4 subjects who receive 3 injections with normal saline placebo. Subjects who complete all immunizations will receive a total 2.7 x 10\^6 PfSPZ. VE will be assessed by exposure to PfSPZ Challenge (7G8) (cryopreserved infectious sporozoites originating from a Pf strain isolated in Brazil, and thus heterologous to the vaccine). The day of CHMI will vary per group with Groups A, B and C receiving PfSPZ Challenge (7G8) on days 14, 42 or 70 after Vaccination 3 (V3), respectively. Direct observation will be for 30 minutes following each dose of PfSPZ Vaccine or PfSPZ Challenge. A research/safety monitor and a Safety Monitoring Committee (SMC) will provide safety oversight. Clinical study monitoring will be the responsibility of Sanaria or Sanaria's designated and authorized representative. Screening will not precede enrollment by more than 90 days. For the second and third immunizations, allowable windows are assigned. The entire study will take approximately 8 months to complete, including 2 months of recruitment because the study will be conducted in two sequential cohorts. The period of follow-up for each immunized subject and placebo controls is through 8 weeks post-CHMI. Study participation will last between 99 and 154 days (not including screening) depending upon group assignment.

Case report forms (CRFs) will serve as the repository of source documents and other relevant data for each study subject. Only information that cannot be collected initially into the CRF (for instance, EKGs and AE medical records) will first be collected onto separate source documents before transcription into the CRF. Laboratory results will be entered from source documents directly into the database.

Solicited adverse events (AEs) will be collected for 7 days after each immunization. Unsolicited AEs will be collected from the first immunization (V1) until 28 days after the third immunization (V3) and for 28 days after CHMI. Physical exams and medical history will be assessed as indicated. Safety laboratories will be collected at screening, day of V1, 14 days after V2, 7 days after V3, day of CHMI and 28 days after CHMI. Surveillance for SAEs will occur for the duration of the study. Follow-up of AEs (including SAEs) occurs until resolution or stability.

If clinical laboratories expire (meaning they were obtained greater than 90 days prior to planned enrollment), specific safety labs will be repeated for screening purposes. Safety evaluation includes an electrocardiogram (ECG) performed at screening. Subjects with abnormal cardiovascular symptoms or findings that appear clinically significant will be excluded and if appropriate, referred to a cardiologist for further evaluation.Clinical laboratory testings will be conducted by Fred Hutchinson Cancer Research Center.

Detection of parasitemia post CHMI will be based upon qRT-PCR. Subjects who have 2 positive qRT-PCR results separated by greater than or equal to 12 hours or a single qRT-PCR result reading \> 250 estimated parasites/mL will be treated with anti-malaria therapy. Anti-malarial therapy will consist of: First-line: Malarone, Second-line: Coartem.