Study of Controlled Human Malaria Infections to Evaluate Protection After Intravenous or Intramuscular Administration of PfSPZ Vaccine in Malaria-Naive Adults
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

      - People bitten by mosquitoes carrying weakened malaria parasites could fight off the disease
      if later exposed to normal malaria parasites. Scientists have discovered how to make the
      weakened parasites, which can be injected by the PfSPZ vaccine. Researchers want to see if
      people who receive the vaccine get malaria after being bitten in a controlled setting (a
      controlled human malaria infection, CHMI).

      Objective:

      - To see if the PfSPZ malaria vaccine is safe and prevents malaria in a controlled setting.

      Eligibility:

      - Healthy adults 18 45 years old.

      Design:

        -  Participants will be screened with medical history, physical exam, blood and lab tests,
           and EKG.

        -  Participants will be split into 8 groups, to be in the study for 3 12 months.

        -  Participants will receive 3 5 vaccinations, injected by a needle in an arm vein or
           muscle.

        -  Participants will keep a health diary and be contacted by phone.

        -  For CHMI, a cup with mosquitoes carrying malaria is applied to participants arm for 5
           minutes. Five mosquitoes at a time are used, until 5 have bitten. Some groups will be
           exposed to malaria more than once.

        -  After CHMI, participants will visit the clinic very frequently (including daily visits
           for 12 days) for 28 days.

        -  Blood will be drawn at most visits, from 1 to 20 tubes. Physical exam and medical
           history may also be repeated

        -  Participants who develop malaria will be treated immediately at the clinic. Standard
           treatment takes 72 hours. Malaria symptoms may last up to 3 days.
    

Detailed description: 
      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.
    

Intervention name(s): PfSPZ Vaccine
Intervention type(s): Biological
Intervention description(s): The PfSPZ Vaccine is composed of radiation-attenuated Plasmodium falciparum sporozoites (PfSPZ) and is designed to prevent malaria in adults, children, and infants. It is formulated in phosphate buffered saline (PBS) with 1% human serum albumin (HSA). Sanaria Incorporated (Sanaria), Rockville, Maryland, developed and produced the PfSPZ Vaccine.
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Healthy Subjects; Vaccine-Mediated Protection; Immunogenicity; Sporozoites; Parasitemia