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

NCT02015091). VRC 314 was designed as an open-label evaluation of the safety, tolerability, immunogenicity, and protective efficacy of the PfSPZ Vaccine. This study was designed to substantiate the initial results with the IV vaccination route for protection against CHMI that was observed in VRC 312 (NCT01441167). 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 was 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 received PfSPZ IM, with half of the amount administered in each arm on a schedule with 4 vaccination. The primary objectives of the study were 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 was related to the durability of protection at 20-26 weeks after the last vaccination, and exploratory objectives were related to the immunogenicity of the PfSPZ Vaccine and identifying potential immune correlates of protection. To further determine potential molecular correlates of immunogenicity and/or protection, RNA-seq was performed on whole blood collected from subjects in all dose groups at time points before, during, and after immunization.]]>
INCLUSION CRITERIA:

18 to 45 years old adults.
Able and willing to participate for the duration of the study.
Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process.
Able and willing to complete the informed consent process.
Willing to donate blood for sample storage to be used for future research.
Willing to refrain from blood donation to blood banks for 3 years following P. falciparum CHMI.
Agrees not to travel to a malaria-endemic region during the entire course of study participation.
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.
If enrolling into a Group with an IV vaccination schedule, then the physical exam must include an assessment that there is adequate bilateral antecubital fossa venous access.

LABORATORY CRITERIA WITHIN 56 DAYS PRIOR TO ENROLLMENT:

Hemoglobin greater than or equal to 11.2 g/dL for women; greater than or equal to 12.6 g/dL for men.
Differential and platelet count either within institutional normal range or accompanied by site physician approval.
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.
Serum creatinine less than or equal to the upper limit of normal.
Negative for HIV infection.

LABORATORY CRITERION DOCUMENTED ANY TIME PRIOR TO ENROLLMENT:

Negative sickle cell screening test.

FEMALE-SPECIFIC CRITERIA:

Negative Beta-HCG pregnancy test (urine or serum) on day of enrollment for women presumed to be of childbearing potential.
A woman of childbearing potential must agree to use an effective means of birth control throughout the duration of study participation.

EXCLUSION CRITERIA:

Woman who is breast-feeding or planning to become pregnant during the time interval needed to complete the study.
Receipt of a malaria vaccine in a prior clinical trial.
Any history of malaria infection.
Evidence of increased cardiovascular disease risk; defined as >10% five-year risk by the non-laboratory method.
Current use of systemic immunosuppressant pharmacotherapy.
History of a splenectomy, sickle cell disease or sickle cell trait.
Plan for major surgery between enrollment and challenge.
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.
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.
Personal beliefs that prohibit the receiving of vaccine products containing human serum albumin within the diluent.
Use or planned use of any drug with the anti-malarial activity that would coincide with study vaccination 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.
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.
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.

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Study Start Date: December 12, 2013Study Completion Date: September 8, 2016
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