Study of the Safety and Immunogenicity of Pfs230D1M-EPA/Alhydrogel and Pfs25M-EPA/Alhydrogel , a Transmission Blocking Vaccine Against Plasmodium Falciparum Malaria, in Adults in the U.S. and Mali
Condition: Malaria
MeSH terms: Malaria; Malaria, Falciparum
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

      - Malaria is a severe infection caused by a parasite. People can get malaria if a mosquito
      that carries the parasite bites them. Malaria infection does not happen in the United States,
      but many people in Africa, Asia, and South America are at risk for it. Researchers want to
      test two vaccines that may help decrease malaria infection.

      Objective:

      - To see if two vaccines (Pfs25M-EPA/Alhydrogel and Pfs230DIM-EPA/Alhydrogel ) are safe in
      humans and cause an immune response that will prevent malaria parasites from correctly
      growing in the mosquito.

      Eligibility:

      - Healthy adults ages 18 50.

      Design:

        -  There are several groups in this study. Each group will receive a different dose of the
           vaccine and some groups will received both vaccines.

        -  Vaccinations will be given on two days about 4 weeks apart.

        -  Participants will receive each vaccine as an injection into the arm. Blood will be drawn
           on the day of vaccination.

        -  In the 4 weeks after receiving a vaccination, participants will have at least 3 clinic
           visits and 1 phone contact. They will have at least 3 more visits and 3 phone contacts
           over the next 6 months.

        -  At each visit, participants will be evaluated for side effects to the vaccine and any
           new health changes or problems. They will be asked how they are feeling and if they have
           taken any medicine. Blood and urine samples may be taken at the visit. More follow-up
           visits may be needed to follow up on changes or problems.
    

Detailed description: 
      A vaccine to interrupt malaria transmission would be a valuable tool for local elimination or

      eradication of this disease. Pfs25 and Pfs230, surface antigens of zygotes and ookinetes in
      the mosquito stage of Plasmodium falciparum, are the lead candidates for a malaria
      transmission blocking vaccine. Recombinant Pfs25M and recombinant Pfs230D1M have each been
      conjugated to Pseudomonas aeruginosa ExoProtein A (EPA) and adjuvanted with Alhydrogel . This
      dose-escalating phase 1 study will determine safety and immunogenicity of these vaccines in
      US adults and subsequently in Malian adults.

      A total of 260 subjects will be enrolled at sites in the US and Mali to receive escalating
      doses of Pfs25M- EPA/Alhydrogel , Pfs230D1M-EPA/Alhydrogel , or simultaneous
      Pfs25MEPA/Alhydrogel and Pfs230D1M-EPA/Alhydrogel . Enrollment within each group will be
      staggered for additional safety, and subjects will only be enrolled into the simultaneous
      administration group once each individual dose has been administered and reviewed for safety.
      Subjects will be followed for at least 6 months after the last vaccination. Safety outcomes
      will be local and systemic adverse events (AEs) and serious adverse events (SAEs).
      Immunogenicity outcomes will be antibody responses as measured by ELISA against recombinant
      Pfs25, Pfs230, and EPA, and B cell responses. Functional activity of the induced antibodies
      will be assessed by membrane feeding assays conducted at the National Institute of Allergy
      and Infectious Diseases in the US.
    

Intervention name(s): Pfs230D1M-EPA/Alhydrogel; Pfs25M-EPA/Alhydrogel; TWINRIX; Menactra
Intervention type(s): Biological; Biological; Drug; Drug
Intervention MeSH terms: Aluminum Hydroxide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: Assays; Antibody; Reactogenicity; Mosquito; Responses