Characterization of Skin Immunity to Aedes Aegypti Saliva in Dengue-endemic Participants in Cambodia
Condition: Vector Borne Diseases
MeSH terms: Vector Borne Diseases
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

      Mosquito-borne viruses like dengue cause major illness and death worldwide, particularly in
      Southeast Asia. When mosquitoes deliver a virus into the skin of humans, they also leave
      saliva. Researchers want to learn more about skin immunity to mosquito saliva. They hope this
      will help with future vaccines and treatments for these diseases.

      Objective:

      To compare the early and late innate immune response in the skin of Aedes aegypti bitten
      versus unbitten skin.

      Eligibility:

      Healthy people ages 18-45 who live within about 15 km of the study site in Chbar Mon

      Design:

      Participants will have 3 visits.

      The baseline/screening visit will include:

      Medical and medication history

      Questions about participants demographic information, mosquito biting risk factors, and
      responses to mosquito or other insect bites

      Physical exam

      Urine sample for some participants

      Mosquito feeding. A feeding device will be placed on the participant s arm for up to 20
      minutes. The insects will feed through a mesh on the bottom of the feeding device.
      Participants may be given standard treatments for any skin reactions.

      Blood tests

      Four skin biopsies taken from bitten and unbitten skin. Local anesthetic will be
      administered, and a small tool will be used to remove the participant s skin.

      Participants will have a second visit the next day. They will have a physical exam and blood
      tests. They will have 1 skin biopsy.

      Participants will have a final visit about 2 weeks later. They will have a physical exam and
      blood tests.

      During the study, participants will be asked to take measures to prevent more mosquito bites.
    

Detailed description: 
      Mosquito-borne viruses continue to cause significant global morbidity and mortality,
      particularly in Southeast Asia. When mosquitoes deliver the virus into the skin of humans
      while probing for a blood meal, they deposit also saliva, which contains a myriad of
      pharmacologically active compounds that modulate the host immune system. Little is known
      about skin immunity to mosquito saliva, particularly in endemic volunteers as most clinical
      studies are performed in na(SqrRoot) ve individuals who have never or rarely been exposed to
      a particular mosquito vector. People living in endemic areas have had long-term repeated
      exposure to these vectors and therefore have different immune response to mosquito saliva,
      which could interfere with mosquito-borne disease vaccine effectiveness. Characterization of
      skin immunity via various technical modalities will be important in order to identify
      critical aspects of the innate and adaptive immune responses after a vector bite.

      Here, we will execute a paired study of exposed-unexposed skin to carefully examine the
      innate and adaptive immune responses in the skin and blood to exposure of the saliva of Aedes
      aegypti, the mosquito vector of dengue, Zika, and chikungunya viruses. We will enroll 42
      participants to undergo vector feeding and give blood samples at baseline and 2 and 14 days
      later. Additionally, participants will give skin punch biopsy samples of bitten (exposed) and
      unbitten (unexposed) skin. For analysis, we will group 10-12 participants in each of 4
      technical modality cohorts or groups : 1) immunohistochemistry, 2) RNA sequencing, 3) flow
      cytometry, and 4) T-cell receptor sequencing. With the current rise of vector-borne diseases
      in the United States and around the world, we hope the results of this study contribute to
      future vaccine design and clinical development strategies for vector#borne diseases.
    

Intervention name(s): Mosquito Feeding
Intervention type(s): Other
Intervention description(s): Mosquito feedings will be conducted with Aedes aegypti colonies raised at the CNM (National Malaria Center) Malaria and Vector Research Laboratory (MVRL), an established state of the art insectaries for mosquitoes was built in 2014 to ACL2 (arthropodcontainment level 2)-level specifications.
Intervention model: Single Group Assignment
Intervention model description: Participants were all exposed to 5 uninfected Aedes aegypti mosquitos on their forearm. Biopsies were taken of bitten and unbitten skin.
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Vector-Borne Diseases; Immune Response; Mosquito Feeding; Arbovirus; Southeast Asia