Safety and Immunogenicity of a First-in-Human Mosquito Saliva Peptide Vaccine
Condition: Mosquito-Borne Disease
MeSH terms: Vector Borne Diseases
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): AGS-v; AGS-v + adjuvant; Placebo
Intervention type(s): Biological; Biological; Other
Intervention description(s): AGS-v (unadjuvanted) as a suspension in WFI (0.5mL) on Day 0 and on Day 21; ISA-51-adjuvanted AGS-v emulsified in WFI (0.5mL) on Day 0 and on Day 21; WFI (0.5mL) on Day 0 and Day 21
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Other
Keywords: Mosquito-Borne Diseases; Universal Mosquito Vaccine; Mosquito Transmission; Vector Borne Viruses; Vaccine