A Phase 1/2 interventional study of Xenodiagnosis Ticks and skin biopsy in Tick-borne Diseases, Tick Resistance and Lyme Disease, sponsored by National Institute of Allergy and Infectious Diseases (NIAID). Recruiting at 1 site in United States. Open to participants aged 18 Years to 99 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-09-22.
Sponsored by National Institute of Allergy and Infectious Diseases (NIAID) · Phase 1/2, Interventional, and Diagnostic
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.
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
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:
Exploratory Objectives:
repeatedly bitten on larvae gene expression.
Endpoints:
Primary Endpoints:
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.
Exploratory Endpoints:
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:
Measurement of changes will be assessed by:
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).
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.
91 studies on the registry are indexed under Lyme Disease; 27 are open to participants now.
This study's planned enrollment of 60 is below the median of 100 across 49 interventional studies indexed under Lyme Disease.
Browse Lyme Disease studies →National Institute of Allergy and Infectious Diseases (NIAID) is the lead sponsor of 2,401 studies on the registry; 179 are open to participants now.
Of its 396 completed or terminated interventional studies of FDA-regulated products, 294 (74%) have results posted.
Counted across the registry records on this site, refreshed daily.
In order to be eligible to participate in this study, an individual must meet all of the following criteria:
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
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
EXCLUSION CRITERIA:
An individual who meets any of the following criteria will be excluded from participation in this 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.
Healthy Volunteer
Device: Xenodiagnosis Ticks · Procedure: skin biopsy · Procedure: blood draw
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.
2-3 mm skin punch biopsies will be performed.
Peripheral blood draws will be performed.
Assessment of Safety of the device. Use toxicity tables and safety monitoring as specified in the protocol.
Ongoing assessment of safety.
Time frame: continuous
Develop a model of acquired tick resistance in humans. Use validated pruritus scales, numerical rating system, verbal rating system, and visual analogue system.
Clinical measures of tick immunity.
Time frame: end of study
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...
Compare changes in early and late local immune response and cellular recruitment between the 1st and 3rd tick exposures.
Time frame: continuous
Exploratory: Analyze gene expression of Ixodes scapularis after feeding on humans using RNASeq.
Measure changes in gene expression of ticks fed at the various time points.
Time frame: continuous
Exploratory: Compare early and late immune response in skin after Ixodes scapularis bite. Use RNASeq, histology, immunohistochemistry, digital spatial profiling to explore.
Compare early and late immune response in the skin using skin biopsies collected at Day 1 and Day 4.
Time frame: 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.
Compare the development of antibody responses against Ixodes scapularis salivary antigens between the 1st, 2nd, and 3rd tick feedings.
Time frame: continous
Plan to share: Undecided — 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.
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Tick-Borne Diseases
National Institute of Allergy and Infectious Diseases (NIAID)