| Eligibility |
Inclusion Criteria:
1. Healthy adults (males and non-pregnant, non-lactating females) between the ages of 18
and 45 years, inclusive
2. Able and willing to participate for the duration of the study
3. Able and willing to provide written (not proxy) informed consent
4. Provides informed consent and correctly answers > / = 70 percent on the post consent
quiz before any study procedures and is available for all study visits
5. Females of childbearing potential and males must agree to practice highly effective
contraception*
*Contraception must be practiced from 30 days before the time of enrollment until at
least 30 days following the third vaccine dose for groups 1, 2 and 3, and the malaria
challenge event for groups 4, 4B, 5 and 6 (such as double barrier methods (condoms
plus foam or spermicide, diaphragm plus foam or spermicide), licensed intrauterine
devices (IUDs), intravaginal or intra/transdermal or oral hormonal methods initiated
at least 30 days before inoculation or challenge, documented surgical sterilization
via tubal ligation the essure procedure or hysterectomy, abstinence or a vasectomized
partner). The contraceptive method should remain unchanged throughout the study
participation
6. Is in good health, as determined by vital signs (heart rate, blood pressure, oral
temperature); medical history; laboratory values* that do not meet toxicity grading
criteria, except when Grade 1 and clinically insignificant; and a physical examination
*Laboratory values include: hemoglobin, white blood cell count, platelet count,
glucose (random), serum alanine aminotransferase (ALT), serum creatinine, urine
protein and urine blood
7. Agree not to travel to a malaria endemic region during the entire course of the trial
8. Willing to avoid non-study related blood donation for the duration of participation in
the study or until at least 1 year after receiving the last investigational vaccine,
whichever is longer
9. Able to understand and comply with planned study procedures including daily outpatient
follow-up visits beginning 5 days after malaria challenge (groups 4, 4B, 5 and 6 only)
10. Willing to avoid non-study related blood donation for 3 years following P. falciparum
challenge (groups 4, 4B, 5 and 6 only)
Exclusion Criteria:
1. Any history of malaria infection, or travel to a malaria endemic region within 6
months before first vaccination
2. History of long-term residence (> / = 5 years) in an area known to have significant
transmission of P. falciparum
3. Positive serology for human immunodeficiency virus (HIV), hepatitis C virus (HCV), or
hepatitis B surface antigen (HBsAg)
4. Positive sickle cell screening test or known hemoglobinopathy (groups 4, 4B, 5 and 6
only)
5. Current or recent (within the last four weeks) treatment with parenteral or oral
corticosteroids (intranasal or inhaled steroids are acceptable), or other
immunosuppressive agents, or chemotherapy
6. History of splenectomy
7. Participants who have a clinically significant (as determined by the PI or designee)
baseline Grade 1 or greater toxicity, or any Grade 2 or greater toxicity (regardless
of clinical significance) by the toxicity table, except hematuria > 1+ detected during
menses for females*
* For females who are menstruating, urinalysis frequently tests positive for blood and
is not an indicator of poor health status or increased risk.
8. Vaccination with a live vaccine within the past 30 days or with a nonreplicating,
inactivated, or subunit vaccine within the last 14 days
9. Known hypersensitivity to components of the vaccine for groups 1, 2, 3, 4, 4B and 5;
or to the adjuvant for groups 1, 2, 4, 4B and 5
10. History of acute or chronic medical conditions including, but not limited to,
disorders of the liver, kidney, lung, heart, nervous system, or other metabolic or
autoimmune/inflammatory conditions
11. History of anaphylaxis or severe hypersensitivity reaction
12. History of Guillain-Barre syndrome or severe adverse reaction to any vaccination
13. Severe asthma, as defined by an emergency room visit or hospitalization within the
last 12 months
14. Pregnant or breastfeeding women or women who plan to become pregnant before day 115 in
groups 1, 2 and 3; or before 30 days post-malaria challenge in groups 4, 4B, 5 and 6
15. Concurrent participation in other investigational protocols prior to Day 141 or
receipt of an investigational product within the previous 30 days
16. Planned receipt of an investigational product within 28 days following the last
vaccination dose or malaria challenge
17. Any condition that, in the opinion of the investigator, would affect a participant's
ability to understand or comply with the study protocol or would jeopardize a
participant's safety or rights
18. History of previous receipt of a candidate malaria vaccine or a vaccine containing the
GLA-LSQ adjuvant
19. Use or planned use of any drug with anti-malarial* activity 30 days before, or after
malaria challenge (groups 4, 4B, 5 and 6 only)
*Medications with antimalarial activity include trimethoprim-sulfamethoxazole,
azithromycin, erythromycin, tetracycline, doxycycline, minocycline, clindamycin,
ciprofloxacin, levofloxacin, norfloxacin and rifampin
20. Planned surgery 30 days before or after vaccination or malaria challenge
21. History of drug or alcohol abuse within the last five years
22. Receipt of blood or blood products in the previous six months or donation of a unit of
blood within two months before screening
23. History of schizophrenia, bipolar disorder or other psychiatric condition that makes
study compliance difficult*
* Subjects with psychoses or history of suicide attempt or gesture in the 3 years
before study entry, ongoing risk for suicide
24. History of diabetes mellitus with the exception of pregnancy-induced diabetes that has
resolved
25. Has evidence of increased cardiovascular disease risk* (defined as > 10 percent, 5
year risk) as determined by the method of Gaziano (groups 4, 4B, 5 and 6 only)
* Risk factors include sex, age (years), systolic blood pressure (mm Hg), smoking
status, body mass index (BMI, kg / mm^2), reported diabetes status, and blood pressure
26. Abnormal screening ECG* (groups 4, 4B, 5, and 6 only)
* Pathologic Q wave and significant ST-T wave changes, left ventricular hypertrophy,
non-sinus rhythm except isolated premature atrial or ventricular contractions, right
of left bundle branch block, advanced A-V heart block (secondary or tertiary), QT/QTc
interval > 450 ms
27. Known hypersensitivity to mosquito bites, artemether-lumefantrine or
atovaquone-proguanil (groups 4, 4B, 5 and 6 only)
28. Anticipated medication use during the 28-day post-challenge period that are known to
interact with artemether/lumefantrine or atovaquone/proguanil, such as cimetidine,
metoclopramide, antacids, and kaolin (groups 4, 4B, 5 and 6 only)
29. Previous participation in a CHMI study
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