First-in-Human PfSPZ-LARC2 Vaccination/CHMI

This randomized, double-blind, placebo-controlled, Phase 1 trial will enroll up to 22 malaria-naïve, adult participants to test safety, tolerability, immunogenicity, and efficacy of the genetically attenuated Plasmodium falciparum sporozoite vaccine (PfSPZ-LARC2) Vaccine. PfSPZ-LARC2 Vaccine is a late-arresting, replication-competent whole Plasmodium falciparum sporozoite product. We hypothesize that the PfSPZ-LARC2 Vaccine will be safe from breakthrough infection by virtue of deletion of two key parasite genes Mei2 and LINUP and may be more immunogenic and protective than previously tested early arresting sporozoite vaccines. The primary objective is to assess the tolerability and safety of administration of PfSPZ-LARC2 Vaccine, with special attention to the adequacy of attenuation.

Inclusion Criteria: 1. Provides written informed consent prior to the initiation of any study procedures. 2. Able to understand and agrees to adhere to all planned study procedures and be available for all study visits. 3. Male or non-pregnant female, 18 to 45 years of age (inclusive) at time of enrollment. 4. BMI 18.0-35.0 kg/m\^2 at screening. 5. Females of childbearing potential\* must agree to use or have practiced true abstinence\*\* or use at least one acceptable primary form of contraception\*\*\*,\*\*\*\*,\*\*\*\*\* Note: These criteria are applicable to females in a heterosexual relationship and child-bearing potential (i.e., the criteria do not apply to participants in a same sex relationship). \*Not of childbearing potential - post-menopausal females (defined as having a history of amenorrhea for at least one year) or a documented status as being surgically sterile (hysterectomy, bilateral oophorectomy, tubal ligation/salpingectomy, or Essure(R) placement). \*\*True abstinence is 100 percent of time no sexual intercourse (male's penis enters the female's vagina). (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception). If true abstinence changes, then participant agrees to use at least one form of acceptable primary contraception. \*\*\*Acceptable forms of primary contraception include monogamous relationship with a vasectomized partner who has been vasectomized for 180 days or more prior to the participant's enrollment visit (Visit 1), intrauterine devices, birth control pills, barrier methods with spermicide and injectable/implantable/insertable hormonal birth control products. * Must use at least one acceptable primary form of contraception for at least 30 days prior to the enrollment visit (Visit 1) and at least one acceptable primary form of contraception for 60 days after the last vaccination or until 28 days post-CHMI, whichever is later. * If the participant is treated with Coartem(R) (artemether/lumefantrine - second-line anti-malarial treatment in this study), participants must agree to add an additional barrier method of contraception during treatment. 6. Females of childbearing potential must have a negative urine or serum pregnancy test within 24 hours prior to enrollment. 7. Males of childbearing potential: use condoms with a female partner of childbearing potential from their enrollment visit (Visit 1), to 60 days after last vaccination or 28 days post-Controlled Human Malaria Infection (CHMI), whichever is later.\*,\*\* \*This does not apply to males in an exclusively same-sex relationship. \*\*Biological males who are post-pubertal and considered fertile until permanently sterile by bilateral orchiectomy or vasectomy. 8. Male participants agree to refrain from sperm donation from the time of first vaccination until 60 days after the last vaccination or until 28 days post-CHMI, whichever is later. 9. In good health\* \*As determined by medical history and physical examination to evaluate acute or ongoing chronic medical diagnoses/conditions that have been present for at least 90 days, which would affect the assessment of safety of participants. Chronic medical diagnoses/conditions should be stable for the last 60 days (no hospitalizations, ER, or urgent care for condition or need for supplemental oxygen). This includes no change in chronic prescription medication, dose, or frequency as a result of deterioration of the chronic medical diagnosis/condition in the 60 days before enrollment. Any prescription change that is due to change of health care provider, insurance company, etc., or done for financial reasons, and in the same class of medication, will not be considered a deviation of this inclusion criterion. Any change in prescription medication due to improvement of a disease outcome, as determined by the participating site PI or appropriate sub-investigator, will not be considered a deviation of this inclusion criterion. Participants may be on chronic or as needed (prn) medications if, in the opinion of the participating site PI or appropriate sub-investigator, they pose no additional risk to participant safety or assessment of reactogenicity and immunogenicity, and do not indicate a worsening of medical diagnosis/condition. Similarly, medication changes subsequent to enrollment and study vaccination are acceptable provided the change was not precipitated by deterioration in the chronic medical condition, and there is no anticipated additional risk to the participant or interference with the evaluation of responses to study vaccination. 10. Oral temperature is less than 100.4 degrees F (38 degrees C). 11. Resting pulse, no greater than 100 beats per minute. 12. Systolic BP is \