Defining Skin Immunity of a Bite of Key Insect Vectors in Humans
Condition: Zika; Dengue; Malaria; Chikungunya; Leishmaniasis
MeSH terms: Leishmaniasis
Study type: Interventional

Summary: 
      Background:

      Mosquitoes and similar insects called sand flies carry parasites that can cause diseases.
      These viruses and parasites can spread quickly and be difficult to control. How people s
      bodies respond to insect bites may affect how they get infected. The response to bites is
      caused by the immune system, which helps fight off infections. Researchers want to study the
      immune response in skin to mosquito or sand fly bites and how the response changes after
      bites on multiple days. This may help researchers develop better vaccines.

      Objective:

      To study the immune response in skin to certain insect bites and how that changes after bites
      on multiple days.

      Eligibility:

      Healthy adults ages 18-64

      Design:

      Participants will be screened under another protocol. Women must agree to practice effective
      contraception or abstinence. All participants must agree to not donate blood or use certain
      lotions or creams on visit days.

      Some participants will have 2 visits over a week. Others will have 5 visits over 8 weeks.

      All participants will have the following at least once:

      Medical history

      Physical exam

      Blood and urine collected

      Mosquito or sand fly feeding. Up to 10 insects will feed on participant s arm for up to 20
      minutes. The insects are grown at NIH and do not carry any diseases. The skin will be checked
      and bites will be treated.

      Skin samples taken. The skin will be cleaned and numbed. A tool will remove a small piece of
      skin from 3 places on the arm.

      About a week after the last visit, participants will be called to see how they feel.
    

Detailed description: 
      Vector-borne diseases continue to cause significant morbidity and mortality worldwide despite
      ongoing control efforts. Vectors like sand flies and mosquitoes deliver the pathogen into the
      skin of humans while taking a blood meal. Most vaccines under development ignore the
      importance of the complex infectious inoculum delivered by the vector and the local immune
      response that occurs at the site of the bite. In addition, many preclinical studies are
      carried out in animal models that do not replicate the natural route of infection,
      transmission by vector bites, and often bypass the skin interface altogether. As such, these
      studies do not evaluate what role the vector plays in the initiation of these infections.
      Further compounding this problem, many clinical studies are performed in naïve individuals
      who have never been exposed to the vector, while those living in endemic areas will have had
      long-term exposure to vectors through uninfected bites.

      A cumulative body of evidence from animal models demonstrates that a variety of
      vector-derived components are co-delivered with the pathogen and may play an important role
      in the establishment of infection. There is limited knowledge of the effect of these
      vector-derived factors on the immune response in human skin and their potential impact on
      infection establishment.

      In this protocol, we will examine the early skin immune response to bites of three
      arthropods: the mosquito Aedes aegypti, the vector of Zika, dengue, and chikungunya viruses;
      the mosquito Anopheles gambiae, the vector of malaria; and the sand fly Lutzomyia
      longipalpis, the vector of leishmaniasis. We will also explore how multiple vector bite
      exposures over time modulate future immune response at the bite site. Healthy participants
      will come to the National Institutes of Health (NIH) and undergo feeding by one of the three
      vectors, then have three skin punch biopsies performed by trained medical practitioners to
      evaluate local immune response. Participants in Cohort A will have one feeding; participants
      in Cohort B will have 4 feedings, each 2 weeks apart. Biopsies will be collected after the
      final feeding. Blood will be collected after the one feeding in Cohort A and after the fourth
      and final feeding in Cohort B to assess systemic immune response.

      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): One vector feeding; Four vector feeding
Intervention type(s): Other; Other
Intervention description(s): Participants will undergo one feeding by one of three colony- reared vectors (Aedes aegypti mosquitos, Anopheles gambiae mosquitos, or Lutzomyia longipalpis sand flies); Participants will undergo four feedings by one of three colony- reared vectors (Aedes aegypti mosquitos, Anopheles gambiae mosquitos, or Lutzomyia longipalpis sand flies), each about 2 weeks apart, with the same vector type.
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Mosquito; Saliva; Immune Response; Sand Fly; Biopsy