Testing Pfs25-EPA/Alhydrogel as a Potential Malaria Transmission Blocking Vaccine
- Conditions
- Malaria
- Interventions
- Biological: Pfs25-EPA/AlhydrogelBiological: Euvax BBiological: Menactra
- Registration Number
- NCT01867463
- Brief Summary
Background:
- Malaria is a disease that is spread by mosquitoes. Researchers are looking for a vaccine that can prevent mosquitoes from transmitting malaria to people. They want to test a vaccine called Pfs25-EPA/Alhydrogel that may help stop malaria parasites from developing in mosquitoes. When a mosquito bites a vaccinated person, the vaccine should prevent parasites from developing in the mosquito. As a result, the mosquito will not spread malaria to the next person it bites. However, the vaccine will not directly prevent people vaccinated from getting sick with malaria. Researchers want to test this vaccine in people who live in rural Mali. To do so, the study will compare the symptoms and the blood tests of the participants who receive either the study vaccine or a regular hepatitis B/meningococcal vaccine.
Objectives:
- To see if Pfs25-EPA/Alhydrogel is a safe and effective malaria vaccine.
Eligibility:
- Healthy volunteers between 18 and 45 years of age who live in Bancoumana, Mali.
Design:
* Participants will be screened with a medical history, physical exam, and blood tests.
* Participants will be separated into two groups. One group will have Pfs25-EPA/Alhydrogel to test the study vaccine. The other group will have the regular Hepatitis B vaccine series, meningococcal vaccine.
* In the study vaccine group, participants will have either a lower dose or a higher dose. For the lower dose, they will have two vaccine shots over 1 year. For the higher dose, they will have four vaccine shots over about 14 months.
* In the other vaccine group, participants will have the Hepatitis B vaccine series, meningococcal vaccine according to the standard dose schedule.
* All participants will provide regular blood samples for testing during the study.
* Participants who develop malaria during the study will participate in evaluation of transmission and parasite development of malaria parasite from the person to mosquito via transmission assays. They will allow mosquitoes (that have no diseases) to bite them in a controlled clinic setting. This will let researchers see if the vaccine can stop the mosquitoes from carrying malaria to other people.
- Detailed Description
A vaccine to interrupt malaria transmission would be a valuable tool for local elimination or eradication of this disease. Pfs25, a surface antigen of ookinetes in the mosquito stage of P. falciparum, is a lead candidate for a malaria transmission blocking vaccine. Recombinant Pfs25 has been conjugated to Pseudomonas aeruginosa ExoProtein A (EPA), and adjuvanted with Alhydrogel . This dose escalating, double-blind, randomized controlled trial will determine safety and immunogenicity of the vaccine in malaria exposed adults. One hundred twenty (120) subjects will be enrolled and randomized to receive the low dose (16 g of conjugated Pfs25, n=10), the high dose (47 g of conjugated Pfs25, n=50), or the comparator vaccine (Euvax B for first 3 vaccinations, then Menactra vaccine for the fourth vaccination, n=10 for 2 vaccinations, n=50 for 4 vaccinations). Enrollment within the high dose group will be staggered for additional safety. The low dose and the matching comparator cohort (Group 1) will receive 2 vaccine doses given at 0 and 2 months. For the rest of the subjects, 3 doses will be given at a 0, 2, 4 month dosing intervals, and a fourth (booster) dose will be given 12 months following the third dose at the start of the subsequent transmission season. Subjects will be followed for 12 months following 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 and EPA, and B cell responses. Functional activity of the induced antibody will be assessed by direct transmission blocking assays (direct skin feeds, direct membrane feeding assays) conducted at the Malaria Research and Training Center (MRTC) in Mali and in a standard membrane feeding assay conducted at the National Institute of Allergy and Infectious Diseases (NIAID) in the United States.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 230
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group 1 Pfs25-EPA/Alhydrogel Group 1: n=20, randomized to receive 16 g Pfs25-EPA/Alhydrogel (n=10) or the comparator (EuvaxB, n=10) on D0, D56 Group 2 Pfs25-EPA/Alhydrogel Group 2: n=30, randomized to receive 47 g Pfs25-EPA/Alhydrogel (n=15) or the comparator (EuvaxB and Menactra , n=15) on D0, D56, D112, D480 Group 2 Menactra Group 2: n=30, randomized to receive 47 g Pfs25-EPA/Alhydrogel (n=15) or the comparator (EuvaxB and Menactra , n=15) on D0, D56, D112, D480 Group 3 Menactra Group 3: n=70 randomized to receive 47 g Pfs25-EPA/Alhydrogel (n=35) or the comparator (EuvaxB and Menactra , n=35) on D0, D56, D112, D480 Group 3 Pfs25-EPA/Alhydrogel Group 3: n=70 randomized to receive 47 g Pfs25-EPA/Alhydrogel (n=35) or the comparator (EuvaxB and Menactra , n=35) on D0, D56, D112, D480 Group 1 Euvax B Group 1: n=20, randomized to receive 16 g Pfs25-EPA/Alhydrogel (n=10) or the comparator (EuvaxB, n=10) on D0, D56 Group 3 Euvax B Group 3: n=70 randomized to receive 47 g Pfs25-EPA/Alhydrogel (n=35) or the comparator (EuvaxB and Menactra , n=35) on D0, D56, D112, D480 Group 2 Euvax B Group 2: n=30, randomized to receive 47 g Pfs25-EPA/Alhydrogel (n=15) or the comparator (EuvaxB and Menactra , n=15) on D0, D56, D112, D480
- Primary Outcome Measures
Name Time Method Incidence of local and systemic adverse events and serious adverse events. 12 months following the last vaccination; and for 6 months following the fourth vaccination.
- Secondary Outcome Measures
Name Time Method Antibody responses as measured by ELISA against recombinant Pfs25 and EPA, and B cell responses. Functional activity of the induced antibody will be assessed by direct transmission blocking assays 12 months following the last vaccination; and for 6 months following the fourth vaccination.
Trial Locations
- Locations (1)
Malaria Research and Training Center
🇲🇱Bamako, Mali