Safety and Immunogenicity of a First-in-Human Mosquito Saliva Peptide Vaccine
- Conditions
- Mosquito-Borne Disease
- Interventions
- Biological: AGS-vOther: PlaceboBiological: AGS-v + adjuvant
- Registration Number
- NCT03055000
- Brief Summary
Background:
Mosquitos carry diseases that cause major health problems and death worldwide. The AGS-v vaccine targets proteins in mosquito saliva. This may help prevent many mosquito-borne diseases. It might also reduce the lifespan of the mosquito that bites the vaccinated person.
Objective:
To see if the AGS-v vaccine is safe in humans and how it affects the immune system.
Eligibility:
Healthy adults ages 18-50
Design:
Participants will be screened another study.
Participants will be randomly assigned to get either the vaccine with a booster vaccine, the vaccine without the booster, or a placebo. These are given through a needle in the upper arm.
Participants will have visits that include medical history, physical exam, and blood and urine tests:
Baseline: They will get the vaccine and be monitored for 2 hours.
Follow-up visits 1 and 2 weeks after baseline.
Visit 3 weeks after baseline: They will get the booster and be monitored for 2 hours.
Follow-up visits 1 and 2 weeks after booster visit.
Visit 3-5 weeks after booster visit: This includes mosquito feeding. Mosquitos grown in the lab will be allowed to bite the arm. Blood will be drawn 4 times in the 3 hours after the feeding.
Phone follow-up a few days after the mosquito feeding.
After the feeding visit, 5 follow-up visits about every 2 months
Participants will keep a symptom diary for 7 days after each vaccine. They will record their temperature. They will measure any redness around the injection site. They will document and if possible photograph any mosquito bites they get.
- Detailed Description
Mosquito-borne diseases continue to cause significant morbidity and mortality worldwide despite on-going control efforts. In 2015, there were \>200 million cases of malaria worldwide, causing nearly half a million deaths, with most of the deaths occurring among children under the age of 5 years. Mosquitos also transmit arboviruses, including dengue, yellow fever, West Nile virus, chikungunya, Rift Valley fever, Japanese encephalitis, and Zika virus. The current new outbreak of Zika virus in Central and South America, as well as the Caribbean, serves as a reminder of how quickly these viruses can spread and how difficult they can be to control.
In this protocol we plan to perform a Phase I study of a novel universal mosquito-borne disease vaccine. Through modulation of the immune system after a mosquito feeding, this vaccine targets the vector saliva and may provide prophylaxis against multiple arboviral and protozoal diseases. In addition the vaccine potentially leads to a reduced mosquito lifespan after feeding therefore also reducing transmission of these diseases.
In this protocol we hope to demonstrate the safety of this vaccine similar to SEEK s other peptide based vaccines Flu-v and HIV-v that have been found to have very good safety profiles in previous Phase I trials. We also hope to demonstrate immunomodulation after a controlled clean Aedes aegypti mosquito feeding to demonstrate proof of concept efficacy of the vaccine. With the current rise of Zika in the Americas and the threat of local mosquito transmission in the U.S. and the rest of the world, a successful universal mosquito-borne disease vaccine offers the benefit of targeting this emerging disease as well as the many established infections such as dengue and malaria that make dealing with this newly emerging epidemic a challenge.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 49
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description AGS-v AGS-v AGS-v (unadjuvanted) as a suspension in WFI (0.5mL) on Day 0 and on Day 21 Placebo Placebo WFI (0.5mL) on Day 0 and Day 21 AGS-v with adjuvant AGS-v + adjuvant ISA-51-adjuvanted AGS-v emulsified in WFI (0.5mL)on Day 0 and on Day 21
- Primary Outcome Measures
Name Time Method Total AGS-v Specific Immunoglobulin 21 days after last vaccination Total AGS-v specific immunoglobulin measured in serum 14 days after the first and/or second vaccination.
IL-10 Cytokine Level as Measured by Luminex 21 days after last vaccination Interferon-gamma and other cytokine markers of Th1 and Th2 response measured in vitro from PBMCs incubated with AGS-v antigens as indicators of Th1 vs. Th2 response
IL-4 Cytokine Level as Measured by Luminex 21 days after last vaccination Interferon-gamma and other cytokine markers of Th1 and Th2 response measured in vitro from PBMCs incubated with AGS-v antigens as indicators of Th1 vs. Th2 response
GM-CSF Cytokine Level as Measured by Luminex 21 days after last vaccination Interferon-gamma and other cytokine markers of Th1 and Th2 response measured in vitro from PBMCs incubated with AGS-v antigens as indicators of Th1 vs. Th2 response
IL-2 Cytokine Level as Measured by Luminex 21 days after last vaccination Interferon-gamma and other cytokine markers of Th1 and Th2 response measured in vitro from PBMCs incubated with AGS-v antigens as indicators of Th1 vs. Th2 response
IL-5 Cytokine Level as Measured by Luminex 21 days after last vaccination Interferon-gamma and other cytokine markers of Th1 and Th2 response measured in vitro from PBMCs incubated with AGS-v antigens as indicators of Th1 vs. Th2 response
Interferon-gamma Cytokine Level as Measured by Luminex 21 days after last vaccination Interferon-gamma and other cytokine markers of Th1 and Th2 response measured in vitro from PBMCs incubated with AGS-v antigens as indicators of Th1 vs. Th2 response
AEs Grade 3 or Higher 1 year after vaccination (study duration) Grade 3 or higher adverse events identified within 1 year after 2 vaccinations 21 days apart.
Number of Subjects With 1 or More Aes 1 year after vaccination (study duration) Percent of people with an AE
IL-1B Cytokine Level as Measured by Luminex 21 days after last vaccination Interferon-gamma and other cytokine markers of Th1 and Th2 response measured in vitro from PBMCs incubated with AGS-v antigens as indicators of Th1 vs. Th2 response
Number of Subjects With 1 or More Grade 3 or Higher AE 1 year after vaccination (study duration) Percent of people with a Grade 3 or higher AE
TNF-a Cytokine Level as Measured by Luminex 21 days after last vaccination Interferon-gamma and other cytokine markers of Th1 and Th2 response measured in vitro from PBMCs incubated with AGS-v antigens as indicators of Th1 vs. Th2 response
- Secondary Outcome Measures
Name Time Method IL-1B Cytokine Level as Measured by Luminex 60 days after Day 42 Mosquito Feeding Interferon-gamma and other cytokine markers of Th1 and Th2 response measured in vitro from PBMCs incubated with AGS-v antigens as indicators of Th1 vs. Th2 response
Number of Pupae Hatched of 100 Eggs Day 42 Mosquito feeding Measurement of changes to Aedes aegypti mosquito life cycle post feeding on blood from participants after vaccination
IL-10 Cytokine Level as Measured by Luminex 60 days after Day 42 Mosquito Feeding Interferon-gamma and other cytokine markers of Th1 and Th2 response measured in vitro from PBMCs incubated with AGS-v antigens as indicators of Th1 vs. Th2 response
Total AGS-v Specific Immunoglobulin 60 days after Day 42 Mosquito Feeding Total AGS-v specific immunoglobulin measured in serum after the first and/or second vaccination.
Number of Adults Developed From 100 Eggs Day 42 Mosquito feeding Measurement of changes to Aedes aegypti mosquito life cycle post feeding on blood from participants after vaccination
Percent of Pupae That Developed Into Adults Day 42 Mosquito feeding Measurement of changes to Aedes aegypti mosquito life cycle post feeding on blood from participants after vaccination
TNF-a Cytokine Level as Measured by Luminex 60 days after Day 42 Mosquito Feeding Interferon-gamma and other cytokine markers of Th1 and Th2 response measured in vitro from PBMCs incubated with AGS-v antigens as indicators of Th1 vs. Th2 response
GM-CSF Cytokine Level as Measured by Luminex 60 days after Day 42 Mosquito Feeding Interferon-gamma and other cytokine markers of Th1 and Th2 response measured in vitro from PBMCs incubated with AGS-v antigens as indicators of Th1 vs. Th2 response
IL-4 Cytokine Level as Measured by Luminex 60 days after Day 42 Mosquito Feeding Interferon-gamma and other cytokine markers of Th1 and Th2 response measured in vitro from PBMCs incubated with AGS-v antigens as indicators of Th1 vs. Th2 response
Number of Eggs Laid Day 42 Mosquito feeding Measurement of changes to Aedes aegypti mosquito life cycle post feeding on blood from participants after vaccination
IL-2 Cytokine Level as Measured by Luminex 60 days after Day 42 Mosquito Feeding Interferon-gamma and other cytokine markers of Th1 and Th2 response measured in vitro from PBMCs incubated with AGS-v antigens as indicators of Th1 vs. Th2 response
IL-5 Cytokine Level as Measured by Luminex 60 days after Day 42 Mosquito Feeding Interferon-gamma and other cytokine markers of Th1 and Th2 response measured in vitro from PBMCs incubated with AGS-v antigens as indicators of Th1 vs. Th2 response
Interferon-gamma Cytokine Level as Measured by Luminex 60 days after Day 42 Mosquito Feeding Interferon-gamma and other cytokine markers of Th1 and Th2 response measured in vitro from PBMCs incubated with AGS-v antigens as indicators of Th1 vs. Th2 response
Percent of Eggs That Developed Into Pupae Day 42 Mosquito feeding Measurement of changes to Aedes aegypti mosquito life cycle post feeding on blood from participants after vaccination
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States