A Clinical Trial of the PfSPZ Vaccine Administered by Direct Venous Inoculation in Healthy Malaria-Naïve Adults: Heterologous vs. Homologous Controlled Human Malaria Infection and Reduction in Number of Doses

Inclusion Criteria: * Healthy adults (male or non-pregnant female) 18 - 45 years of age, inclusive. * Able and willing to participate for the duration of the study. * Able and willing to provide written (not proxy) informed consent. * Women of childbearing potential must agree to use effective means of birth control (e.g. oral or implanted contraceptives, IUD, female condom, diaphragm with spermicide, cervical cap, abstinence, use of a condom by the sexual partner or sterile sexual partner) during the entire study. Women with a history of surgical or chemical sterilization (e.g. tubal ligation, hysterectomy, other) must provide written documentation of infertility from a Primary Care Provider. * Willing to refrain from blood donation (except as required in this study) for 3 years following CHMI. * Agree not to travel to a malaria endemic region during the entire course of the trial. Exclusion Criteria: * Any history of malaria infection, or travel to a malaria endemic region within 6 months prior to first immunization. * History of long-term residence (\>5 years) in area known to have significant transmission of P. falciparum. * Has evidence of increased cardiovascular disease risk (defined as \> 10%, 5 year risk) as determined by the method of Gaziano \[Gaziano, 2008\]. Risk factors include sex, age, systolic blood pressure (mm Hg), smoking status, body mass index (BMI, kg/mm2), and reported diabetes status. * Positive HIV, HBsAg or HCV serology. * Positive sickle cell screening test. * An abnormal electrocardiogram, defined as one showing pathologic Q waves and significant ST-T wave changes; left ventricular hypertrophy; any non-sinus rhythm including isolated premature ventricular contractions, but excluding isolated premature atrial contractions; right or left bundle branch block; or advanced (secondary or tertiary) A-V heart block. * Current use of systemic immunosuppressant pharmacotherapy. * Current significant medical condition (cardiovascular, hepatic, renal, or hematological) or evidence of any other serious underlying medical condition identified by medical history, physical examination, or laboratory examination. * History of a splenectomy. * History of neurologic disorder (including seizures) or migraine headache. * History of psychiatric disorders (such as personality disorders, anxiety disorders, or schizophrenia) or behavioral tendencies (including active alcohol or drug abuse) discovered during the screening process that in the opinion of the investigator would make compliance with the protocol difficult. * Plan for surgery between enrollment and CHMI. * Females who are pregnant or nursing, females who plan on becoming pregnant or plan to nurse during the study period. * Known allergy to any component of the vaccine formulation, history of anaphylactic response to mosquito-bites, or any history of anaphylactic reaction, retinal or visual field changes, or known allergy to anti-malarials including chloroquine phosphate, atovaquone/proguanil (Malarone®), or artemether/lumefantrine (Coartem®) * Receipt of another investigational vaccine or drug within 30 days prior to the first immunization, or plan to participate in another investigational vaccine/drug research during or within 1 month following participation in this study. * Receipt of more than three other vaccines within 60 days prior to the screening visit, or plan to receive more than three other vaccines during or within 1 month following participation in this study. * Personal beliefs that prohibit the receiving of vaccine product containing human serum albumin within the diluent (vaccine recipients only). * Use or planned use of any drug with anti-malarial activity that would coincide with the periods of immunization or CHMI. * History of psoriasis or porphyria, which may be exacerbated after treatment with chloroquine. * Anticipated use of medications known to cause drug reactions with chloroquine, atovaquone-proguanil (Malarone®), or artemether/lumefantrine (Coartem®) such as cimetidine, metoclopramide, antacids, and kaolin. * History of any other illness or condition which, in the investigator's judgment, may substantially increase the risk associated with the subject's participation in the protocol or compromise the scientific objectives.