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Menselijke immuunrespons op tekenbeten van Ixodes Scapularis

19 september 2026 bijgewerkt door: National Institute of Allergy and Infectious Diseases (NIAID)

Onderzoek naar de menselijke immuunrespons op tekenbeten van Ixodes Scapularis

Background:

Each year, the number of cases of tick-borne diseases increases. The deer tick (Ixodes scapularis) is the vector of at least 7 pathogens that cause human diseases, including Lyme disease. Researchers want to learn more to help them develop vaccines against ticks in the future.

Objective:

To learn how people s bodies, particularly the skin, respond to tick bites.

Eligibility:

Healthy adults aged 18 years and older who have no known history of a tick-borne disease or tick bite exposure.

Design:

Participants will be screened with a medical history, physical exam, and blood tests.

Participants will have 2 skin punch biopsies of healthy skin. For this, a sharp instrument will be used to remove a round plug of skin about the size of a pencil eraser. Participants will then have 10 clean laboratory-bred ticks placed at 2 different sites on their skin (20 ticks total). The ticks will be removed from the first site 1 day after placement and from the second site 2-4 days after placement. Participants will complete symptom diary cards. They will answer questions about itching at the tick feeding sites. They will give blood samples. Photos will be taken of the tick feeding sites. Skin punch biopsies will be collected at the sites of the tick bites.

Participants will repeat the tick feeding procedures 2 times, each 2-8 weeks apart. For the 2nd and 3rd procedures, 10 clean laboratory-bred ticks will be placed at 1 site. The ticks will be removed 2-3 days after tick placement. They will have telephone follow-up visits after each procedure.

After the final tick removal, participants will have follow-up visits in 4-6 weeks and again in 3 months. They will give blood samples and discuss how they are feeling.

Participation will last about 5-7 months.

Studie Overzicht

Toestand

Werving

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

Study Description:

This study aims to develop a model for acquired tick resistance in humans, characterize the acquisition of tick-associated skin immunity, and monitor the innate and adaptive immune response of Ixodes scapularis tick bites. The study will be a prospective, non-randomized, single-center study performed at the National Institutes of Health (NIH) Clinical Center. It will be performed under Investigational Device Exemption (IDE) G210153 and will be monitored as per National Institute of Allergy and Infectious Diseases (NIAID) and NIH regulations. Participants (35 adult healthy volunteers) will undergo up to 3 tick feeding placements, 2 to 8 weeks

apart. One to two punch skin biopsies (2-3 mm) from the tick bite sites will be collected at 1 day (early) and 2-4 days (late) after the first tick placement procedure. Skin biopsies of an unaffected site will be performed as a control. One to two punch skin biopsies (2-3 mm) from the tick bite sites will be collected at day 2-3 after the 2nd and 3rd tick placement procedures. Additionally, blood will be collected to evaluate systemic immune response to tick salivary proteins. Ticks will also be collected at each timepoint and gene expression will be analyzed to determine the effect of the human skin response on ticks.

Changes in resistance to tick bites can be evaluated by:

  • Local reaction to the tick bite

    • pruritus
    • site reactions
    • Blood flow index as measured by laser speckle contrast imaging

  • Number of fed ticks

Changes in the immune response and cellular recruitment in the skin can be evaluated using:

Differential expression of immune transcripts and other skin associated transcripts using RNAseq or other high-throughput profiling of cells.

Conventional histology and immunohistochemistry

Digital Spatial Profiling to determine cell type and other immune markers using a high-plex platform

Changes in the systemic immune response will be evaluated by:

Measurement of antibodies against tick salivary proteins will be assessed by enzyme-linked immunosorbent assay (ELISA) and

western blot

Novel state-of-the-art high-resolution technologies to deeply characterize the immune response to tick bites over time, both phenotypically and functionally.

Changes in tick transcriptomic profile will be assessed by:

RNAseq: Ribonucleic acid (RNA) will be isolated from tick after they have been removed from subjects and unexposed ticks.

Differential expression profile will be performed and validated by NanoString

Objectives:

Primary Objectives:

  1. Develop a model of acquired tick resistance in humans
  2. Continue to assess the safety of tick feeding using laboratory-reared Ixodes scapularis larva in humans

Exploratory Objectives:

  1. Comparison of the early and late immune response in the skin site of the bite of Ixodes scapularis after a single tick exposure.
  2. Determine the effects of repeated tick feeding on the immune response at the tick bite site in human skin and development of tick resistance.
  3. Analyze the evolution of the systemic immune response to tick bite in participants after multiple tick exposures and validate development of reliable biomarkers of tick exposure.
  4. Analyze gene expression of Ixodes scapularis larvae feeding on humans and determine the effects of immune response of subjects

repeatedly bitten on larvae gene expression.

Endpoints:

Primary Endpoints:

  1. Pruritus at the site of tick attachment in the first 24 hours of tick placement over the three placements as measured by a positive slope

    over the three placements of the numerical rating score. The slope of other pruritus scores at 24 hours and at Day 2-4, and the number of attached ticks collected from participants over the three placements will also be measured.

  2. Monitor safety adverse events (AEs) using reporting tools and Sponsor safety monitors.

Exploratory Endpoints:

  1. Compare the results from the skin biopsies acquired with the first tick placement. Our hypothesis is that there will be differential phenotypic, transcriptomic, and immunohistochemical differences between:

    • Exposed (bitten skin at day 1) and unexposed (unbitten skin)
    • Exposed (bitten skin at day 2-4) and unexposed (unbitten skin)
    • Exposed (bitten skin at day 1) and exposed (bitten skin at day 2-4)

    Measurement of changes will be assessed by:

    • Differential expression of immune transcripts and other skin associated transcripts using RNAseq
    • Conventional histology and immunohistochemistry
    • Digital Spatial Profiling to determine cell type and other immune markers using a high-plex platform

  2. Compare the changes in the local immune response and cellular recruitment between the 1st, 2nd and the 3rd tick exposures and correlate with measures of itching, blood flow index and number of attached ticks and the feeding status.

    We postulate that differences between the timepoints will become more marked with multiple exposures. We hypothesize that there will be differential phenotypic and transcriptomic differences between:

    Exposed (bitten skin at day 2-3, exposure 2) and exposed (bitten skin at day 2-3, exposure 3)

    Correlate these changes with measures of resistance to tick feeding (itching, number and level of feeding of attached ticks, blood flow index).

  3. Compare the development of antibody responses against Ixodes scapularis salivary protein antigens between the 1st, 2nd, and the 3rd tick exposures and correlate antibodies against tick salivary proteins with measures of resistance (itching, erythema, blood flow index, number of fed ticks).

    Explore the development of the host response in blood using high resolution technologies such as immunophenotyping, proteomics and

    transcriptomics and compare the responses between the 1st, 2nd, and the 3rd tick exposures.

  4. Using RNAseq technology, measure changes in gene expression of ticks fed at early timepoint (1 day) vs late timepoint (2-4 days) vs unfed ticks and of ticks fed at 1st, 2nd, and 3rd placements. Correlation of pruritus and changes in tick gene expression.

Studietype

Ingrijpend

Inschrijving (Geschat)

60

Fase

  • Fase 2
  • 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.

Studiecontact

Studie Contact Back-up

Studie Locaties

  • Verenigde Staten
    • Maryland
      • Bethesda, Maryland, Verenigde Staten, 20892
        • Werving
        • National Institutes of Health Clinical Center
        • Contact:
          • For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)
          • Telefoonnummer: TTY8664111010 800-411-1222
          • E-mail: prpl@cc.nih.gov

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 99 jaar (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Ja

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:

  1. Stated willingness to comply with all study procedures and availability for the duration of the study.

  2. Age 18 years or older.

  3. In good general health as evidenced by medical history.

  4. No history of TBD.

  5. No known tick bite.

  6. Serum IgE level within Clinical Center Department of Laboratory Medicine normal range.

    https://ccinternal2.cc.nih.gov/LTGRA/UL/public_labtest_detail.aspx?next_flg=Y&test_id=4731&id_order=53

  7. Serum tryptase level within Clinical Center Department of Laboratory Medicine normal range.

    https://ccinternal2.cc.nih.gov/LTGRA/UL/public_labtest_detail.aspx?next_flg=Y&test_id=1157&id_order=1

  8. For participants of child-bearing potential: use of effective contraception for at least 1 month prior to tick placement, and agreement to use such a method during study participation and for an additional 3 months after the removal of the last ticks. Types of contraception include abstinence, surgical methods (sterilization, implants, intrauterine device, partner with vasectomy), hormonal methods (birth control pill, patch, ring, injection), or barrier methods (diaphragm plus spermicide, male condom plus spermicide)

  9. For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner.

  10. Agree to not participate in other clinical studies requiring investigational interventions for the duration of the study.

  11. Minimum hemoglobin of 13.0 g/dL for males and 12 g/dL for females

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this study:

  1. History of forming large thick scars (keloids) after skin injuries.
  2. History of excessive bleeding after cuts or procedures.
  3. History of taking anticoagulants in the past 28 days.
  4. History of allergic reaction to lidocaine.
  5. History of allergic reaction to tape, adhesive bandages, or dressings.
  6. Inability to maintain the dressing for any reason.
  7. Pregnancy or lactation.
  8. Treatment with another investigational drug or other intervention within the past 30 days.
  9. Oral or intravenous (IV) steroids in the 2 weeks prior to each tick placement procedure (topical, nasal, inhaled, intra-articular, and replacement doses of steroids are not exclusions).
  10. History of reactions to mammalian meat, IgE- mediated food allergies, urticaria or anaphylaxis. Mild pollen-food allergy syndrome is not an exclusion.
  11. History of systemic allergic reaction to venom (bee, wasps and other Hymenoptera stings).
  12. History of clinically significant drug allergies.
  13. History of moderate to severe atopy asthma, atopic dermatitis, allergic rhinitis.
  14. Active severe skin disease, uncontrolled diabetes, cancer other than non-melanoma skin cancers, autoimmune disease requiring immunosuppressive therapy, or history of human immunodeficiency virus (HIV), chronic viral hepatitis, or syphilis.
  15. Refusal to allow storage of samples and data for future usage.
  16. Any other condition that, in the opinion of the investigator, would make the patient unsuitable for enrollment or could interfere with the patient participating in and completing the study.

Exclusion of Select Populations:

Children:

Children are excluded from this protocol as there is no direct benefit to the participants, the risk from the skin biopsies is small but above minimal, the procedure is invasive and can be stressful for children, and there is concern over their ability to maintain the LeFlap dressing.

Pregnant and breastfeeding women:

Pregnant and breastfeeding women are excluded from trial participation as there is no direct benefit to the participants.

Adults who lack or lose decision-making capacity to consent to research participation:

Adults lacking decision-making capacity to provide informed consent are excluded at screening as there is no direct benefit to the participants. Enrolled participants who permanently or temporarily lose the ability to consent after receiving the first tick exposure procedure will be advised to continue study visits for safety monitoring but will have no additional research procedures performed.

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: Diagnostisch
  • Toewijzing: NVT
  • Interventioneel model: Opdracht voor een enkele groep
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Actieve vergelijker: 1

Healthy Volunteer
Apparaat: Xenodiagnosis Ticks

Larval ticks will be obtained from Dr. Sam Telford from a laboratory maintained tick colony at Tufts Veterinary School. These ticks are hatched from eggs laid by ticks that have fed only on specific pathogen free laboratory animals that were purchased from established vendors.

Procedure: skin biopsy

2-3 mm skin punch biopsies will be performed.

Procedure: blood draw

Peripheral blood draws will be performed.

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Assessment of Safety of the device. Use toxicity tables and safety monitoring as specified in the protocol.
Tijdsspanne: continuous

Ongoing assessment of safety.
continuous
Develop a model of acquired tick resistance in humans. Use validated pruritus scales, numerical rating system, verbal rating system, and visual analogue system.
Tijdsspanne: end of study

Clinical measures of tick immunity.
end of study

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Exploratory: Determine the effects of repeated tick feeding on immune response at tick bite site and the development of resistance. Use RNASeq,histology, immunohistochemistry, digital spatial profiling, clinical itch scales, site reactions, tick...
Tijdsspanne: continuous

Compare changes in early and late local immune response and cellular recruitment between the 1st and 3rd tick exposures.
continuous
Exploratory: Analyze gene expression of Ixodes scapularis after feeding on humans using RNASeq.
Tijdsspanne: continuous

Measure changes in gene expression of ticks fed at the various time points.
continuous
Exploratory: Compare early and late immune response in skin after Ixodes scapularis bite. Use RNASeq, histology, immunohistochemistry, digital spatial profiling to explore.
Tijdsspanne: continuous

Compare early and late immune response in the skin using skin biopsies collected at Day 1 and Day 4.
continuous
Exploratory: Analyze the evolution of the systemic immune response to tick bite by measuring antibodies response (ELISA and western blot) against Ixodes scapularis salivary protein antigens.
Tijdsspanne: continous

Compare the development of antibody responses against Ixodes scapularis salivary antigens between the 1st, 2nd, and 3rd tick feedings.
continous

Medewerkers en onderzoekers

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

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Onderzoekers

  • Hoofdonderzoeker: Adriana R Marques, M.D., 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

Nuttige links

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)

28 februari 2022

Primaire voltooiing (Geschat)

30 juni 2029

Studie voltooiing (Geschat)

30 juni 2029

Studieregistratiedata

Eerst ingediend

4 september 2021

Eerst ingediend dat voldeed aan de QC-criteria

7 september 2021

Eerst geplaatst (Werkelijk)

8 september 2021

Updates van studierecords

Laatste update geplaatst (Werkelijk)

22 september 2026

Laatste update ingediend die voldeed aan QC-criteria

19 september 2026

Laatst geverifieerd

16 september 2026

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • 10000331
  • 000331-I

Plan Individuele Deelnemersgegevens (IPD)

Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?

ONBESLIST

Beschrijving IPD-plan

It is not yet known if the research results will reveal a need to disclose IPD, therefore it is undecided if we plan to make IPD available.

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Nee

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Ja

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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