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

21 maart 2022 bijgewerkt door: National Institute of Allergy and Infectious Diseases (NIAID)

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

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.

Studie Overzicht

Toestand

Voltooid

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

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.

Studietype

Ingrijpend

Inschrijving (Werkelijk)

42

Fase

  • Fase 1

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

  • Cambodja
      • Chbar Mon, Cambodja, 05251
        • Kampong Speu Referral Hoispital

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar tot 45 jaar (Volwassen)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

  • INCLUSION CRITERIA:

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).

EXCLUSION CRITERIA:

-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.

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Fundamentele wetenschap
  • Toewijzing: NVT
  • Interventioneel model: Opdracht voor een enkele groep
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: Mosquito Feeding
Each participant will receive one mosquito feeding with 5 starved female Aedes aegypti mosquitoes.
Ander: Mosquito Feeding
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.

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Measurement of Change in Early and Late Innate Immune Responses Using Gene Expression and Flow Cytometry in Participants' Skin
Tijdsspanne: Day 0 timepoints
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.
Tijdsspanne: Day 2 (48 hr post feeding)
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)

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Flow Cytometry Analysis of PBMCs Collected Day 0 (Baseline) and Days 2 and 14 After Feeding for Saliva-specific T-cells
Tijdsspanne: Day 14
Describing and understanding cellular immunity to Aedes saliva in heavily exposed individuals will simulate endemic conditions and will inform vaccine design in these target populations.
Day 14

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Algemene publicaties

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

27 oktober 2020

Primaire voltooiing (Werkelijk)

9 april 2021

Studie voltooiing (Werkelijk)

9 april 2021

Studieregistratiedata

Eerst ingediend

16 april 2020

Eerst ingediend dat voldeed aan de QC-criteria

16 april 2020

Eerst geplaatst (Werkelijk)

17 april 2020

Updates van studierecords

Laatste update geplaatst (Werkelijk)

12 april 2022

Laatste update ingediend die voldeed aan QC-criteria

21 maart 2022

Laatst geverifieerd

9 april 2021

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • 999920053
  • 20-I-N053

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Nee

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

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