Study of Controlled Human Malaria Infections to Evaluate Protection After Intravenous or Intramuscular Administration of PfSPZ Vaccine in Malaria-Naive Adults

VRC 314 is designed as an open-label evaluation of the safety, tolerability, immunogenicity
and protective efficacy of PfSPZ Vaccine. This vaccine administered at 1.35 times 10(5) PfSPZ
per injection by the IV route on a schedule of 5 vaccinations was previously shown to confer
protection in all vaccinated subjects against CHMI performed shortly after last vaccination;
however there was limited durability of protection in a small number of protected subjects
who were rechallenged several months later. This study is designed to substantiate the
initial results with the IV vaccination route for protection against CHMI. Based on the
potential importance of dose and schedule in optimizing sustained immunity with this vaccine,
an increase in PfSPZ IV dosage on schedules of 3 to 5 vaccinations will be evaluated for
protection against CHMI conducted early (about 3 weeks) and late (about 24 weeks) after
completion of vaccinations. To assess if a higher dose given by another route confers
protection, one group will receive PfSPZ IM, with half of the amount administered in each arm
on a schedule with 4 vaccination.

The primary objectives of the study are related to the safety and tolerability of
vaccinations by the IV and IM routes of administration and protection against Plasmodium
falciparum (Pf) challenge performed via a well-established CHMI procedure early (2-4 weeks)
after completing schedules of 3 to 5 vaccinations. The secondary objective is related to the
durability of protection at 20-26 weeks after the last vaccination and exploratory objectives
are related to the immunogenicity of the PfSPZ Vaccine and identifying potential immune
correlates of protection.

- INCLUSION CRITERIA:

A volunteer must meet all of the following criteria to be included:

1. 18 to 45 years old adults.

2. Able and willing to participate for the duration of the study.

3. Able to provide proof of identity to the satisfaction of the study clinician
completing the enrollment process.

4. Able and willing to complete the informed consent process.

5. Willing to donate blood for sample storage to be used for future research.

6. Willing to refrain from blood donation to blood banks for 3 years following P.
falciparum CHMI.

7. Agrees not to travel to a malaria endemic region during the entire course of study
participation.

8. Physical examination and laboratory results without clinically significant findings
and a body mass index (BMI) less than or equal to 35 for vaccine groups or BMI less
than or equal to 40 for control groups.

9. If enrolling into a Group with an IV vaccination schedule, then the physical exam must
include assessment that there is adequate bilateral antecubital fossa venous access.

Laboratory Criteria within 56 days prior to enrollment:

10. Hemoglobin greater than or equal to 11.2 g/dL for women; greater than or equal to 12.6
g/dL for men.

11. Differential and platelet count either within institutional normal range or
accompanied by site physician approval.

12. Alanine aminotransferase (ALT) less than or equal to 1.25 x upper limit of normal
(ULN) for vaccine groups or less than or equal to 1.75 x ULN for CHMI control groups.

13. Serum creatinine less than or equal to upper limit of normal.

14. Negative for HIV infection.

Laboratory Criterion documented any time prior to enrollment:

15. Negative sickle cell screening test.

Female-Specific Criteria:

16. Negative Beta-HCG pregnancy test (urine or serum) on day of enrollment for women
presumed to be of childbearing potential.

17. A woman of childbearing potential must agree to use an effective means of birth
control throughout the duration of study participation.

EXCLUSION CRITERIA:

A volunteer will be excluded if one or more of the following conditions apply:

1. Woman who is breast-feeding or planning to become pregnant during the time interval
needed to complete the study.

2. Receipt of a malaria vaccine in a prior clinical trial.

3. Any history of malaria infection.

4. Evidence of increased cardiovascular disease risk; defined as >10% five year risk by
the non-laboratory method.

5. Current use of systemic immunosuppressant pharmacotherapy.

6. History of a splenectomy, sickle cell disease or sickle cell trait.

7. Plan for major surgery between enrollment and challenge.

8. Known allergy to any component of the vaccine formulation; history of anaphylactic
response to mosquito-bites; or known allergy to chloroquine phosphate, atovaquone or
proguanil.

9. Participation in any study involving another investigational vaccine or drug within 12
weeks prior to enrollment, or plan to participate in another investigational
vaccine/drug research during the study.

10. Personal beliefs that prohibit the receiving of vaccine product containing human serum
albumin within the diluent.

11. Use or planned use of any drug with anti-malarial activity that would coincide with
study vaccination or challenge.

12. History of psoriasis or porphyria, which may be exacerbated after treatment with
chloroquine.

13. Anticipated use of medications known to cause drug reactions with chloroquine or
atovaquone-proguanil (Malarone) such as cimetidine, metoclopramide, antacids, and
kaolin.

14. Psychiatric condition that precludes compliance with the protocol; past or present
psychoses; disorder requiring lithium; or within five years prior to enrollment,
history of a suicide plan or attempt.

15. Any medical, psychiatric, social condition, occupational reason or other
responsibility that, in the judgment of the investigator, is a contraindication to
protocol participation or impairs a volunteer s ability to give informed consent or to
comply with the protocol schedule.