Defining Skin Immunity of a Bite of Key Insect Vectors in Humans
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|ClinicalTrials.gov Identifier: NCT03641339|
Recruitment Status : Recruiting
First Posted : August 22, 2018
Last Update Posted : September 24, 2018
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.
To study the immune response in skin to certain insect bites and how that changes after bites on multiple days.
Healthy adults ages 18-64
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:
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.
|Condition or disease||Intervention/treatment||Phase|
|Vector-Borne Diseases||Other: Vector Feeding||Phase 1|
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 na(SqrRoot) ve 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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||140 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Defining Skin Immunity of a Bite of Key Insect Vectors in Humans|
|Actual Study Start Date :||September 5, 2018|
|Estimated Primary Completion Date :||May 1, 2019|
|Estimated Study Completion Date :||May 1, 2020|
Participants will be assigned to groups that differ by type of vector and number of feedings. Participants will undergo either 1 feeding (Cohort A) or 4 feedings, each about 2 weeks apart (Cohort B), with the same vector type.
Other: Vector Feeding
Controlled feeding by 1 of 3 colony-reared vectors (Aedes aegypti mosquitos, Anopheles gambiae mosquitos, or Lutzomyia longipalpis sand flies). Participants will undergo either 1 feeding (Cohort A) or 4 feedings, each about 2 weeks apart (Cohort B), with the same vector type.
- To compare the early innate immune response in the skin of bitten (case) versus unbitten (control) skin for each of the three vector groups (Aedes, Anopheles, sand flies). [ Time Frame: 1 yr ]
- To evaluate how multiple exposures over time modulate local skin adaptive immune responses to bites of each of the three vector groups (Aedes, Anopheles, sand flies). [ Time Frame: 1 yr ]
- To analyze systemic immune response to vector salivary proteins in vector-naive participants in each group (Aedes, Anopheles, sand flies). [ Time Frame: 1 yr ]
- To analyze systemic immune response to vector salivary proteins in vector-experienced participants in each group (Aedes, Anopheles,sand flies). [ Time Frame: 1 yr ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03641339
|Contact: Rani S Athota, Ph.D.||(301) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 email@example.com|
|Principal Investigator:||Matthew J Memoli, M.D.||National Institute of Allergy and Infectious Diseases (NIAID)|