Malaria CVD 36000; Gates INV090205

Inclusion criteria

• Male or non-pregnant, non-breastfeeding female between 18 and 50 years of age (inclusive) at the time of consent.
• Participants must be able to provide written informed consent.
• Participants must be healthy as established by medical history and clinical examination at study entry.
• Participants must pass a comprehension (defined as 80%) test and be able to comply with all study requirements.
• Both males and females are eligible to participate as per the following:

Participants physically capable of pregnancy must agree to use effective contraception to avoid pregnancy from 28 days before enrollment through 10 months after last administration of investigational product are eligible to participate. An effective contraceptive method is defined as one that results in a failure rate of less than 1% per year when it is used consistently and correctly. Adequate contraceptive precautions include intrauterine contraceptive device, oral contraceptives, diaphragm, or condom in combination with contraceptive jelly, cream, or foam; Norplant® or Depo-Provera®, through the completion of study visits to minimize any potential risk.

i. Effective contraception does not apply to participants of child-bearing potential with same sex partners, when this is their preferred and usual lifestyle.

ii. Adequate contraception does not apply to women with documented surgical sterility (tubal ligation, bilateral oophorectomy, salpingectomy, or hysterectomy), congenital sterility, who have a diagnosis of infertility and are not undergoing treatment, or women who have not had a menstrual period in at least 1 year

Exclusion criteria

• Women who are pregnant or breastfeeding
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required)
• History of malaria infection, or history > 6 months spent in a malaria endemic region within 5 years prior to enrollment.
• Participant seropositive for hepatitis B surface antigen (HBsAg), hepatitis C virus antibodies (anti-HCV), or human immunodeficiency virus antibodies (anti-HIV).

Note: Prior participants of HIV vaccine studies may result in a false positive HIV antibody test, as such, in this scenario, participant will be eligible if they have a negative HIV RNA PCR at screening.

• Safety laboratory test results within range at screening (as per FDA Toxicity Grading Scale, see Appendix A):

• White Blood Cell (WBC) 3,500-12,000/mm3
• WBC differential either within institutional normal range or accompanied by the PI or designee approval
• Platelets = 125,000 - 500,000/mm3
• Hemoglobin within institutional normal range or accompanied by the PI or designee approval
• Creatinine ≤ 1.1 x upper limit of normal (ULN)
• ALT ≤1.25 x ULN
• Grade 1 subclinical abnormalities in other chemistries will not lead to exclusion if the investigator considers them not clinically significant
• A 5-year cardiovascular risk of >10% using the Gaziano nomogram (Appendix B)
• Significant screening physical examination abnormalities at the discretion of the investigator, including a BMI > 35 kg/m2
• Electrocardiogram (ECG) with clinically significant abnormalities (examples may include: pathologic Q waves, significant ST-T wave changes, left ventricular hypertrophy, any non-sinus rhythm excluding isolated premature atrial contractions, right or left bundle branch block, advanced A-V heart block). ECG abnormalities determined by an investigator to be clinically insignificant as related to trial participation do not preclude trial enrollment. Consultation may be sought by a cardiologist at investigator discretion.
• Known intolerance to atovaquone or proguanil, and either artemether/lumefantrine or chloroquine phosphate
• Routine use of antibiotics, or use of antibiotics with known antimalarial effect (azithromycin, trimethoprim/sulfamethoxazole or tetracyclines) within 4 weeks prior to CHMI.
• Anticipated use of medications known to cause drug reactions with chloroquine or atovaquone-proguanil (Malarone®) such as cimetidine, metoclopramide, antacids, and kaolin.
• Administration of immunoglobulins and/or any blood products during the period starting 90 days preceding the CHMI or planned administration during the study period
• Planned administration or administration of a live vaccine/product not planned in the study protocol during the period starting 30 days prior to the CHMI until the study completion (routine vaccinations will be allowed if it is not administered within 14 days preceding or 21 days following CHMI)
• Use of any investigational or non-registered product (drug or vaccine during the period starting 30 days preceding the CHMI and/or planned use during the study period
• Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting 90days prior to the CHMI (for corticosteroids, this will mean prednisone >5mg/day or equivalent; inhaled, intranasal and topical steroids are allowed)
• Concurrently participating in another clinical study, at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device)
• Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or blood draws
• History of a splenectomy, sickle cell disease or sickle cell trait
• History of skeeter syndrome or anaphylactic response to mosquito-bites
• Autoimmune disease or history of autoimmune disease
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the study product or related to a study procedure
• Major congenital defects or serious chronic illness
• Presence of any implanted device which could bias biosensor data (e.g., pacemaker, etc.)
• Acute disease and/or fever (≥37.5°C/99.5°F oral body temperature) at the time of enrollment: note that a participant with a minor illness such as mild diarrhea, mild upper respiratory infection, etc., without fever, may be enrolled at the discretion of the investigator
• Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic, neurological disorders, seizures or renal functional abnormality, as determined by history, physical examination or laboratory screening tests
• History of bipolar disorder, schizophrenia, hospitalization in the past year for a mental health disorder, or any other psychiatric condition, which in the opinion of the investigator prevents the participant from participating in the study
• Any current medical, psychiatric, occupational, or substance abuse problems that, in the opinion of the Investigator, will make it unlikely that the participant will comply with the protocol.
• Any other condition which, in the opinion of the investigator, prevents the participant from participating in the study