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人体对肩突硬蜱叮咬的免疫反应

2026年9月19日 更新者：National Institute of Allergy and Infectious Diseases (NIAID)

调查人体对肩突硬蜱叮咬的免疫反应

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.

研究概览

地位

招聘中

条件

干预/治疗

详细说明

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.

研究类型

介入性

注册 (估计的)

60

阶段

  • 阶段2
  • 阶段1

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习联系方式

研究联系人备份

学习地点

  • 美国
    • Maryland
      • Bethesda、Maryland、美国、20892
        • 招聘中
        • National Institutes of Health Clinical Center
        • 接触：
          • For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)
          • 电话号码：TTY8664111010 800-411-1222
          • 邮箱：prpl@cc.nih.gov

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 至 99年 (成人、年长者)

接受健康志愿者

是的

有资格学习的性别

全部

描述

  • 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.

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：诊断
  • 分配：不适用
  • 介入模型：单组作业
  • 屏蔽：无（打开标签）

武器和干预

参与者组/臂
干预/治疗
有源比较器：1

Healthy Volunteer
设备：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.

程序：skin biopsy

2-3 mm skin punch biopsies will be performed.

程序：blood draw

Peripheral blood draws will be performed.

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Assessment of Safety of the device. Use toxicity tables and safety monitoring as specified in the protocol.
大体时间：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.
大体时间：end of study

Clinical measures of tick immunity.
end of study

次要结果测量

结果测量
措施说明
大体时间
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...
大体时间：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.
大体时间：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.
大体时间：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.
大体时间：continous

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

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

National Institute of Allergy and Infectious Diseases (NIAID)

调查人员

  • 首席研究员：Adriana R Marques, M.D.、National Institute of Allergy and Infectious Diseases (NIAID)

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

一般刊物

有用的网址

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2022年2月28日

初级完成 (估计的)

2029年6月30日

研究完成 (估计的)

2029年6月30日

研究注册日期

首次提交

2021年9月4日

首先提交符合 QC 标准的

2021年9月7日

首次发布 (实际的)

2021年9月8日

研究记录更新

最后更新发布 (实际的)

2026年9月22日

上次提交的符合 QC 标准的更新

2026年9月19日

最后验证

2026年9月16日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • 10000331
  • 000331-I

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

未定

IPD 计划说明

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.

药物和器械信息、研究文件

研究美国 FDA 监管的药品

不

研究美国 FDA 监管的设备产品

是的

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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