Adenovirus Type 35 Based Circumsporozoite Malaria Vaccine in Burkina Faso
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to evaluate the safety of a malaria vaccine, Ad35.CS.01, and how
      the body reacts to vaccination. Participants will include 48 Berkinabè healthy males and
      females ages 18-45 years in Burkina Faso. Volunteers for this study will be divided into 4
      groups. Members of each group (12 per group) will receive an increasing dose of vaccine or
      placebo (an inactive substance). Ten will receive the malaria vaccine and 2 will receive
      placebo. Study procedures include: physical exam, urine sample, and blood samples.
      Participants will be involved in study related procedures for about 13 months.
    

Detailed description: 
      Malaria currently represents one of the most prevalent infections in tropical and subtropical
      areas throughout the world. Each year, malaria affects around 300 million people and kills 1
      to 3 million people in developing countries. Malaria is caused by the mosquito-borne
      hematoprotozoan parasites belonging to the genus Plasmodium (P.). Malaria parasites have a
      life cycle consisting of several stages. Each one of these stages is able to induce specific
      immune responses against the corresponding stage-specific antigens. Malaria parasites are
      transmitted to man by several species of female Anopheles mosquitoes. Infected mosquitoes
      inject the sporozoite form of the malaria parasite into the mammalian bloodstream. Before
      invading hepatocytes, sporozoites remain for a few minutes in the circulation. At this stage
      the parasite is located in the extracellular environment and is exposed to antibody attack,
      mainly directed to the circumsporozoite (CS) protein, a major component of the sporozoite
      surface. Once in the liver, the parasites replicate and develop into schizonts (up to 20,000
      per infected cell). During this intracellular stage of the parasite, the main effectors of
      the host immune response are T lymphocytes, especially CD8+ T cells. Ad35.CS.01 is a malaria
      vaccine for which a codon optimized nucleotide sequence representing the P. falciparum
      circumsporozoite (CS) surface antigen is inserted in a replication deficient Adenovirus 35
      backbone. It is hypothesized that the Ad35.CS.01 vaccine will prevent the P. falciparum
      parasite, which causes malaria, from entering and developing within the liver of those who
      become infected. Ad35.CS.01 would therefore be expected to reduce malaria-attributable
      morbidity and mortality. The primary objective is to assess the safety and reactogenicity of
      4 ascending dosages of Adenovirus Type 35 circumsporozoite malaria vaccine among healthy,
      semi-immune, subjects given in 3 doses at 0, 1 and 3 months by intramuscular (IM) injection.
      The secondary objective is to evaluate the immunogenicity of the Adenovirus Type 35 based
      circumsporozoite malaria vaccine through performance of Humoral Immune Assays (ELISA
      [enzyme-linked immunosorbent assay] for antibodies to circumsporozoite antigen and Adenovirus
      Neutralization Assay for neutralizing antibodies to Adenovirus Type 35) and Cellular Immune
      Assays (Elispot and Flow Cytometry) for CS-specific CD4+ and CD8+ T cell responses and a
      whole blood ELISA assay to measure secreted cytokines. This is a phase I randomized,
      controlled, double-blinded, dosage-escalation trial to evaluate the immunogenicity, safety,
      and reactogenicity of an Adenovirus Type 35 based circumsporozoite malaria vaccine in
      Burkinabè, in semi-immune, healthy adults 18 to 45 years of age. Researchers propose to
      confirm the safety of each dosage of the new vaccine by assessing safety laboratory
      parameters and reactogenicity for 14 days after the initial dose in the lower dosages before
      escalating to the next dosage level. Each dosage level group will include 10 subjects given
      vaccine intramuscularly. Two subjects in each dosage group will receive normal saline as
      placebo control.
    

Intervention name(s): Ad35.CS.01 Circumsporozoite Malaria Vaccine; Placebo
Intervention type(s): Biological; Drug
Intervention description(s): Ad35.CS.01 appears clear to slightly opalescent with no visible particles. Each 0.75 mL dose of the assigned dosage will be administered via intramuscular injection into the deltoid muscle. Dosages: 10^9 viral particles (vp)/mL, 10^10 vp/mL, 5 x 10^10 vp/mL, and 10^11 vp/mL.; Normal saline placebo control delivered via intramuscular injection into the deltoid muscle.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: malaria, vaccine, Burkina Faso