Defining Skin Immunity of a Bite of Key Insect Vectors in Humans

NCT03641339 | Completed Results

• 2 other identifiers: 18013918-I-0139
• Study Type: interventional
• Target: 95
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Zika; Dengue; Malaria; Chikungunya; Leishmaniasis

Keywords

Mosquito; Saliva; Immune Response; Sand Fly; Biopsy

Outcome Measures

Primary Outcomes (2)

• Number of Differentially Expressed Genes Between Bitten (Case) Versus Unbitten (Control) Skin for Each of the Three Vector Groups

  Number of differentially expressed genes between bitten and unbitten skin with adjusted p-values (adjusted for multiple comparisons) of \< 0.05 and a minimum absolute fold change \> 4 in samples derived from skin biopsies for the three vector groups - Aedes aegypti, Anopheles gambiae, Lutzomyia longipalpis

  Up to 48 hours post bite

• Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups

  Number of participants with certain types of inflammatory cell infiltrates, which includes neutrophils, mononuclear cells, and eosinophils, in the skin biopsies of bitten skin at 30 minutes, 4 hours, and 48 hours post bite for each of the three vector groups - Aedes aegypti, Anopheles gambiae, and Lutzomyia longipalpis

  Up to 48 hours post bite

Study Arms (2)

Cohort A: One vector feeding and three biopsies

EXPERIMENTAL

Undergo one vector feeding and three biopsies on Day 0

Other: One vector feeding

Cohort B: Four vector feedings and three biopsies

EXPERIMENTAL

Undergo 4 vector feedings over 8 weeks and 3 biopsy procedures after the 4th and final feeding

Other: Four vector feeding

Interventions

One vector feeding OTHER

Participants will undergo one feeding by one of three colony- reared vectors (Aedes aegypti mosquitos, Anopheles gambiae mosquitos, or Lutzomyia longipalpis sand flies)

Cohort A: One vector feeding and three biopsies

Four vector feeding OTHER

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.

Cohort B: Four vector feedings and three biopsies

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Individuals must meet all of the following criteria to be eligible for study participation:
• Healthy women and men who are greater than or equal to 18 and less than or equal to 64 years of age.
• Able to provide informed consent.
• Willingness to complete all study visits and comply with all study requirements.
• Willing to have samples stored for future research.
• A female is eligible for this study if she meets 1 of the following:
• Of non-childbearing potential (i.e., women who have had a hysterectomy or tubal ligation or are postmenopausal, as defined by no menses in greater than or equal to 1 year).
• Of childbearing potential but agrees to practice effective contraception or abstinence for 4 weeks prior to enrollment through the completion of the study. Acceptable methods of contraception include a male partner who is sterile and is the sole sexual partner of the female participant or a male partner who uses a condom with spermicide plus 1 or more of the following that is used by the female: 1) implants of levonorgestrel; 2) injectable progestogen; 3) an intrauterine device with a documented failure rate of \<1%; 4) oral contraceptives; and 5) double barrier method including diaphragm.
• Agrees to not use scented lotions, deodorants, or topical creams on each feeding day.
• Agrees to not take aspirin or any other NSAID within 7 days of a biopsy.
• Agrees to not use topical steroid creams or ointments throughout the study without prior permission of Principal Investigator (PI).
• Vector-specific antibody enzyme-linked immunosorbent assay (ELISA) to one of the three vectors (the one to which the individual is assigned) is \<2.5 standard deviations above the negative control for Cohort A only.

You may not qualify if:

• Individuals meeting any of the following criteria will be excluded from study participation:
• Any underlying or current medical condition that, in the opinion of the investigator, would interfere with participation in the study.
• Any participant that is HIV positive.
• A clinically significant (as determined by the PI) baseline Grade 1 or greater toxicity by the toxicity table.
• History of severe allergic reaction (including to mosquito or other insect bites) with generalized urticaria, angioedema, anaphylaxis, or anaphylactoid reaction.
• Prone to allergic responses and/or significant history of allergies, including seasonal or specific allergies as determined by the PI.
• Receipt of any investigational drug that is unlicensed within 3 months or 5.5 half- lives (whichever is greater) prior to enrollment.
• Receipt of any unlicensed vaccine within 6 months prior to enrollment.
• Self-reported or known history of alcoholism or drug abuse within 6 months prior to enrollment, or positive urine test for drugs of abuse at screening (excluding positive test for tetrahydrocannabinol (THC) or its metabolites if usage is less than 3 times per week).
• Self-reported or known history of psychiatric or psychological issues that require treatment and are deemed by the PI to be a contraindication to protocol participation.
• Any use of medications that affect blood clotting within 3 months, history of abnormal blood clotting, or result outside of the normal laboratory range for measurements of prothrombin time (PT), partial thromboplastin time (PTT), or international normalized ratio (INR) that may suggest a problem with blood clotting.
• History of significant scarring after previous biopsies, lacerations, abrasions, surgeries, or other skin procedures (e.g., cosmetic piercings) that are deemed by the PI to be a contraindication to protocol participation.
• Pregnant or breastfeeding.
• Co-enrollment Guidelines: Co-enrollment in other trials is restricted, but may take place after consultation with the study staff and approval from the PI.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (2)

• Fauci AS, Morens DM. Zika Virus in the Americas--Yet Another Arbovirus Threat. N Engl J Med. 2016 Feb 18;374(7):601-4. doi: 10.1056/NEJMp1600297. Epub 2016 Jan 13. No abstract available.

  PMID: 26761185 BACKGROUND

• Edqvist PH, Fagerberg L, Hallstrom BM, Danielsson A, Edlund K, Uhlen M, Ponten F. Expression of human skin-specific genes defined by transcriptomics and antibody-based profiling. J Histochem Cytochem. 2015 Feb;63(2):129-41. doi: 10.1369/0022155414562646. Epub 2014 Nov 19.

  PMID: 25411189 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Zika Virus Infection; Dengue; Malaria; Chikungunya Fever; Leishmaniasis

Condition Hierarchy (Ancestors)

Mosquito-Borne Diseases; Vector Borne Diseases; Infections; Arbovirus Infections; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections; Hemorrhagic Fevers, Viral; Protozoan Infections; Parasitic Diseases; Alphavirus Infections; Togaviridae Infections; Euglenozoa Infections; Skin Diseases, Parasitic; Skin Diseases, Infectious; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Matthew J. Memoli, MD, MS
• Organization: National Institutes of Health

memolim@niaid.nih.gov

301-443-5971

Study Officials

• Matthew J Memoli, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 21, 2018
• First Posted: August 22, 2018
• Study Start: September 5, 2018
• Primary Completion: May 20, 2020
• Study Completion: May 20, 2020
• Last Updated: December 8, 2021
• Results First Posted: December 8, 2021

Record last verified: 2019-08

Locations

US (1)