Characterization of Skin Immunity to Aedes Aegypti Saliva in Dengue-endemic Participants in Cambodia

NCT04350905 | Completed Phase 1 Results

• 2 other identifiers: 99992005320-I-N053
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Vector Borne Diseases

Keywords

Vector-Borne Diseases; Immune Response; Mosquito Feeding; Arbovirus; Southeast Asia

Outcome Measures

Primary Outcomes (2)

• Measurement of Change in Early and Late Innate Immune Responses Using Gene Expression and Flow Cytometry in Participants' Skin

  Measurement of changes in the early and late innate immune response and cellular recruitment in bitten skin versus unbitten skin by: a) immunohistochemistry of target proteins at Day 0 timepoints b) immunophenotyping of innate immune cell subsets in dissociated skin sample at Day 0 timepoints c) determination of cytokine profile in dissociated skin sample supernatant at Day 0 timepoints d) differential cDNA expression prepared from skin RNA and analyzed via RNASeq at Day 0 timepoints

  Day 0 timepoints

• Measurement of Changes in the Adaptive Immune Response and Cellular Recruitment in the Skin of Bitten Versus Unbitten Skin After Sixth and Final Feeding in Each Vector Group.

  Measurement of changes in the adaptive immune response and cellular recruitment in bitten skin versus unbitten skin by: a) immunohistochemistry of target proteins at Day 2 timepoints b) phenotyping of adaptive immune cell subsets in dissociated skin sample at Day 2 timepoints c) determination of cytokine profile in dissociated skin sample supernatant at Day 2 timepoints d) differential cDNA expression prepared from skin RNA and analyzed via RNASeq at Day 2 timepoints

  Day 2 (48 hr post feeding)

Secondary Outcomes (1)

• Flow Cytometry Analysis of PBMCs Collected Day 0 (Baseline) and Days 2 and 14 After Feeding for Saliva-specific T-cells

  Day 14

Study Arms (1)

Mosquito Feeding

EXPERIMENTAL

Each participant will receive one mosquito feeding with 5 starved female Aedes aegypti mosquitoes.

Other: Mosquito Feeding

Interventions

Mosquito Feeding OTHER

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.

Mosquito Feeding

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• In order to be eligible to participate in this study, an individual must meet all of the following criteria:
• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female, aged 18 - 45 years
• Live within approximately 15 km of study site
• In good general health as evidenced by medical history
• Willing to allow biological samples to be 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 \>=1 year).
• Of childbearing potential but has negative urine pregnancy test on Day 0
• Agrees to not use scented lotions, deodorants, or topical creams on each feeding day.
• Agrees to not take aspirin or any other NSAID (ex. ibuprofen) within 7 days of a biopsy.
• Agrees to not use oral or topical antihistamines or steroid creams or ointments throughout the
• study without prior permission of Principal Investigator (PI).

You may not qualify if:

• Any underlying or current medical condition that, in the opinion of the investigator, would
• interfere with participation in the study.
• History of severe allergic reaction (including to mosquito or other insect bites) with generalized
• urticaria, angioedema, anaphylaxis, anaphylactoid reaction or any other reaction described by
• the participant and deemed severe by the PI.
• Self-reported or known history of alcoholism or drug abuse within 6 months prior to enrollment
• 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 or history of abnormal blood
• clotting
• History of significant scarring such as keloids 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.

Sponsors & Collaborators

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

Study Sites (1)

Kampong Speu Referral Hoispital

Chbar Mon, 05251, Cambodia

Location

Related Publications (3)

• Durnez L, Mao S, Denis L, Roelants P, Sochantha T, Coosemans M. Outdoor malaria transmission in forested villages of Cambodia. Malar J. 2013 Sep 17;12:329. doi: 10.1186/1475-2875-12-329.

  PMID: 24044424 BACKGROUND

• Manning JE, Morens DM, Kamhawi S, Valenzuela JG, Memoli M. Mosquito Saliva: The Hope for a Universal Arbovirus Vaccine? J Infect Dis. 2018 Jun 5;218(1):7-15. doi: 10.1093/infdis/jiy179.

  PMID: 29617849 BACKGROUND

• Huy R, Buchy P, Conan A, Ngan C, Ong S, Ali R, Duong V, Yit S, Ung S, Te V, Chroeung N, Pheaktra NC, Uok V, Vong S. National dengue surveillance in Cambodia 1980-2008: epidemiological and virological trends and the impact of vector control. Bull World Health Organ. 2010 Sep 1;88(9):650-7. doi: 10.2471/BLT.09.073908. Epub 2010 Apr 7.

  PMID: 20865069 BACKGROUND

MeSH Terms

Conditions

Vector Borne Diseases

Condition Hierarchy (Ancestors)

Infections

Results Point of Contact

• Title: Jessica Manning
• Organization: NIH

Jessica.manning@nih.gov

+85561856557

Study Officials

• Jessica E Manning, 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: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Model Details: Participants were all exposed to 5 uninfected Aedes aegypti mosquitos on their forearm. Biopsies were taken of bitten and unbitten skin.

Study Record Dates

• First Submitted: April 16, 2020
• First Posted: April 17, 2020
• Study Start: October 27, 2020
• Primary Completion: April 9, 2021
• Study Completion: April 9, 2021
• Last Updated: April 12, 2022
• Results First Posted: April 12, 2022

Record last verified: 2021-04-09

Locations

CA (1)