Safety, Immunogenicity, and Protective Efficacy of Radiation Attenuated Plasmodium Falciparum NF54 Sporozoites in Healthy African Adults in Mali
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

      Malaria is still a health problem in Sub-Saharan Africa. Death rates are stable and have even
      increased in some areas. There are malaria vaccines. However, researchers think repeated
      immunizations with a vaccine called PfSPZ may work better.

      Objective:

      To see if PfSPZ is safe, tolerable, and effective against malaria.

      Eligibility:

      Healthy adults ages 18 to 50 years who live in the Doneguebougou area in Mali

      Design:

      Participants will be screened with medical history and physical exam.

      Participants will sign or fingerprint the consent form. They will take a survey to see how
      well they understand the study.

      Participants will give blood and urine samples.

      Participants will have at least one ECG: Soft electrodes will be stuck to the skin. A machine
      will record heart signals.

      Participants will have HIV counseling.

      Participants will be assigned to a group. Groups will get a different strength doses. Groups
      will get a different number of vaccines over different periods of time.

      If a participant develops a rash or injection site reaction, photographs may be taken.

      Participants will receive an oral anti-malaria drug during the study.

      Participants will be monitored for 3 to 6 months after the last vaccine.
    

Detailed description: 
      It is known that humans can be protected against malaria by repeated immunization with
      radiation attenuated sporozoites. Traditionally, those sporozoites are administered by
      exposing the vaccinee to at least 1000 bites of sporozoite infected irradiated mosquitoes, an
      approach that is unsuitable for mass vaccination campaigns. Recently, Sanaria, Inc. developed
      a process for manufacturing, in compliance with current Good Manufacturing Practices (cGMPs)
      aseptic, purified, radiation attenuated cryopreserved sporozoites from a well characterized
      isolate of P. falciparum (Hoffman et al., 2010). This product, which is called PfSPZ Vaccine,
      can be administered by needle and syringe. Previous studies conducted by the Vaccine Research
      Center and the Navy have established that IV administration of PfSPZ Vaccine can induce
      sterile protection against controlled human malaria infection (CHMI) with a homologous strain
      of P. falciparum in up to 100% of malaria na(SqrRoot) ve individuals (Seder et al., 2013). A
      recent study conducted as collaboration among the Malaria Research and Training Center (MRTC,
      Mali), the Laboratory of Malaria Immunology and Vaccinology (LMIV) National Institute of
      Allergy and Infectious Diseases (NIAID), and Sanaria, Inc. (Sissoko et al., unpublished) has
      shown that sterile protection against naturally occurring malaria infection can be achieved,
      but not at the level seen in the US nor at the level desired.

      The next logical step in an attempt to improve protective efficacy in the targeted endemic
      population is to increase the PfSPZ Vaccine dose, increasing the interval between the first
      and second doses to 8 weeks (as was done in WRAIR 2080 in the group receiving 3 doses of
      4.5x105 PfSPZ), and reducing the numbers of doses to three. Additionally, in this study
      design, we also can begin to understand how the standard controlled human malaria infection
      (CHMI) model may be used in the field and start to explore the impact of such factors as
      malaria co infection and drug treatment have on vaccine responses.

      The initial dose escalation pilot study will focus on safety and tolerability of the PfSPZ
      Vaccine. A defined number of subjects enrolled during the pilot study will also undergo
      further evaluation, including randomization to receive or not receive drug treatment
      immediately prior to each vaccination and examination of protective efficacy against
      homologous CHMI via PfSPZ Challenge. The targeted dose (18x105 PfSPZ Vaccine), if safe and
      tolerable, will be administered to a larger cohort in a double blind, randomized, placebo
      controlled trial to examine the protective efficacy of the vaccine against naturally
      occurring infection. PfSPZ Vaccinees (Arm 2) from the main study will be re enrolled the
      following malaria transmission along with age, sex, and village matched controls (re enrolled
      Arm 3, additional controls) to explore the duration of protection through another malaria
      transmission season.

      Subjects will be recruited from rural villages in Mali. The study will be conducted as
      collaboration among MRTC, LMIV/NIAID, and Sanaria, Inc.
    

Intervention name(s): PfSPZ Vaccine; PfSPZ Challenge Material; PBS and HSA Diluent; Normal Saline; Coartem; ASAQ
Intervention type(s): Biological; Biological; Drug; Other; Drug; Drug
Intervention description(s): PfSPZ Vaccine contains aseptic, purified, vialed, cryopreserved, radiation attenuated NF54 P. falciparum sporozoites. PfSPZ Vaccine will be delivered by DVI in the pilot and main phases of the study. Participants will receive either 1 or 3 injections.; PfSPZ Challenge are aseptic, cryopreserved P. falciparum sporozoites used for CHMI trials. PfSPZ Challenge is not radiated, thus it is fully infections. It will be administered via DVI to participants in Arm 1c and 1d.; The diluent for PfSPZ Vaccine and Challenge is composed of phosphate-buffered saline (PBS) and human serum albumin (HSA). Vials of sterile PBS (1.6ml) and HSA (0.5ml) will be shipped to the clinical site, where diluent composed of PBS and HSA is prepared. HSA is a licensed product which is approved for parenteral, IV administration to humans. The HSA lots are extensively tested to ensure that it is free of infectious agents as listed in the CoA and is approved for use by the Food and Drug Administration(FDA).; Sterile isotonic (0.9%) normal saline will be procured in the US and shipped to Mali at ambient temperature. Like the product, normal saline is a clear liquid, making it indistinguishable from the study product when drawn up into a syringe.; Artemether/lumefantrine (coartem) is a licensed antimalarial in the US and Mali for use for uncomplicated malaria. It has an excellent safety profile and is widely used to treat malaria. Artemether /lumefantrine is a Category C pregnancy drug. Thus all female participants will undergo pregnancy testing prior to receiving this drug.; ASAQ is a fixed dose artemisinin based combination therapy that is indicated and approved for the management of uncomplicated P. falciparum malaria. It has been shown to be as effective as artemether
/lumefantrine when taken at a once/day dosage.
Intervention MeSH terms: Artemether, Lumefantrine Drug Combination
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: Malaria; Cryopreserved; Infection; Human; Immunization