Immunization Via Mosquito Bite With Radiation-attenuated Sporozoites

Inclusion Criteria: * Healthy adults (male or non-pregnant, non-breastfeeding female) 18-50 years of age (inclusive). * Available and willing to participate for duration of study. * Able and willing to provide written informed consent. * Able to complete an Assessment of Understanding with a score of at least 70% correct. * In good general health with no clinically significant health problems as established by medical history, physical exam and laboratory screening. * Females of childbearing potential must have a negative pregnancy test at screening and agree to not become pregnant or breastfeed for the duration of the study. She must be willing to use a reliable form of contraception during the study. Reliable forms of birth control include use of condoms, diaphragm or cervical cap, birth control pills, IUD or sperm killing products. * Agree to refrain from blood donation (except as required in this study) for 3 years following P falciparum challenge. * Agree not to travel to a malaria-endemic region during the study. * Good peripheral venous access. Exclusion Criteria: * Positive HIV, HBsAg, or HCV serology. * Positive sickle cell screening test, including evidence of sickle trait. * Reactivity by CSP or AMA1 ELISpot assay or ELISA as determined by IMRAS Study Specific Procedure #204. * Anemia (below normal reference laboratory value of hemoglobin) on screening. * Weight less than 110 pounds (this does not apply to infectivity controls as it is a weight cut-off for subjects undergoing leukapheresis procedure) * 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 Pf \[cumulative lifetime exposure\]. * Use of systemic immunosuppressant pharmacotherapy for greater than 10 days within 60 days of scheduled first immunization (inhaled and topical steroids are allowed; short duration or tapered corticosteroid regimens of 10 days or less that have been discontinued prior to first immunization are allowed). * Current significant medical condition (cardiovascular, hepatic, renal, pulmonary, or hematological) or evidence of any other serious underlying medical condition identified by medical history, physical examination, or laboratory examination (includes bleeding disorders). * Plan for surgery between enrollment and day 28 post-challenge (minor procedures, elective corrective vision surgery, and dental procedures are allowed). * Receipt of immunoglobulin and/or any blood products within 90 days of scheduled leukapheresis or immunization. Version 13.0 (08May2015) 70 US Government Proprietary Deleted: 8 Deleted: 08JULY2014 * Has evidence of increased cardiovascular disease risk (defined as \> 5%-10%, 5-year risk) as determined by the method of Gaziano (2008). Risk factors include sex, age (years), systolic blood pressure (mm Hg), smoking status, body mass index (BMI, kg/m2), reported diabetes status, and blood pressure. * An abnormal electrocardiogram (ECG), defined as one showing pathologic Q waves and significant ST-T wave changes; left ventricular hypertrophy; any non-sinus rhythm excluding isolated premature atrial contractions; right or left bundle branch block; or advanced (secondary or tertiary) A-V heart block. * History of a splenectomy. * History of any other illness or condition that, in the investigator's judgment, may substantially increase the risk associated with the subject's participation in the protocol or compromise the scientific objectives. This may include 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. * History of anaphylactic or severe response to mosquito bites, retinal or visual field changes, or known allergy to the antimalarial chloroquine phosphate, which will be used to treat subjects developing malaria after CHMI. * Participation in any study involving any investigational vaccine or drug within 30 days prior to the screening visit, or plan to participate in another investigational vaccine/drug research during or within 1 month following participation in this study. * Use or planned use of any drug with antimalarial activity that would coincide with immunization or challenge. * History of psoriasis or porphyria, which may be exacerbated after treatment with chloroquine. * Anticipated use of medications known to cause drug reactions with chloroquine or atovaquone-proguanil (Malarone) such as cimetidine, metoclopramide, antacids, and kaolin during the day 7 to 28 post-challenge period. * Any other significant findings which, in the investigator's judgment, may substantially increase the risk associated with the subject's participation in the study or compromise the scientific objectives.