Human Immune Response to Ixodes Scapularis Tick Bites

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Recruiting

CT.gov ID

NCT05036707

Collaborator

(none)

Enrollment

Location

Arm

21.5

Anticipated Duration (Months)

2.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 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 4-6 weeks apart. 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 7 months.

Condition or Disease	Intervention/Treatment	Phase
Tick-borne Diseases Tick Resistance Lyme Disease	Device: Xenodiagnosis Ticks Procedure: skin biopsy Procedure: blood draw	Phase 1/Phase 2

Detailed Description

Tick-borne diseases (TBDs) are a serious public health problem in the US. Immune responses to multiple tick bites or multiple tick exposures can induce tick-resistance (manifested by reduced numbers and body weights of engorged ticks or tick death in subsequent infestations) in animal models and consequently protection against Borrelia burgdorferi transmission. Similar findings are seen in humans, but little is known about the nature of the protective immune response. Here we propose to combine our expertise to study the response to tick bites in a well standardized clinical setting to identify critical aspects of the human innate and adaptive immune responses in skin and blood following exposure to uninfected Ixodes scapularis ticks; and monitor the acquisition of a tick-associated skin immunity, including itch. This research could lead to the identification of tick salivary proteins that are targets of host immunity and might serve as targets for an anti-tick vaccine. With the current rise of tick-borne diseases in the United States and around the world, we hope the results of this study will contribute to future vaccine design and clinical development strategies for tick-borne diseases.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

Investigating the Human Immune Response to Ixodes Scapularis Tick Bites

Anticipated Study Start Date :

Sep 14, 2021

Anticipated Primary Completion Date :

Jun 30, 2023

Anticipated Study Completion Date :

Jun 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1 Healthy Volunteer	Device: 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.

Arm

Intervention/Treatment

Active Comparator: 1

Healthy Volunteer

Device: 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.

Outcome Measures

Primary Outcome Measures

Assessment of Safety of the device. Use toxicity tables and safety monitoring as specified in the protocol. [continuous]
Ongoing assessment of safety.
Develop a model of acquired tick resistance in humans. Use validated pruritus scales, numerical rating system, verbal rating system, and visual analogue system. [end of study]
Clinical measures of tick immunity.

Secondary Outcome Measures

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... [continuous]
Compare changes in early and late local immune response and cellular recruitment between the 1st and 3rd tick exposures.
Exploratory: Analyze gene expression of Ixodes scapularis after feeding on humans using RNASeq. [continuous]
Measure changes in gene expression of ticks fed at the various time points.
Exploratory: Compare early and late immune response in skin after Ixodes scapularis bite. Use RNASeq, histology, immunohistochemistry, digital spatial profiling to explore. [continuous]
Compare early and late immune response in the skin using skin biopsies collected at Day 1 and Day 4.
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. [continous]
Compare the development of antibody responses against Ixodes scapularis salivary antigens between the 1st, 2nd, and 3rd tick feedings.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

Stated willingness to comply with all study procedures and availability for the duration of the study.
Age 18 years or older.
In good general health as evidenced by medical history.
No history of TBD.
No known tick bite.
Blood group B or AB.
Serum IgE level less or equal to 50 IU/milliliters (mL).
Serum tryptase level less or equal to 7 nanograms (ng)/mL.
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 surgical methods (sterilization, implants, intrauterine device), hormonal methods (birth control pill, patch, ring, injection), or barrier methods (diaphragm plus spermicide, male condom plus spermicide)
For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner.
Agree to not participate in other clinical studies requiring blood draws and/or investigational interventions for the duration of the study.
Minimum hemoglobin of 13.0 g/dL for males and 12.5 g/dL for females.

EXCLUSION CRITERIA:

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

History of forming large thick scars (keloids) after skin injuries.
History of excessive bleeding after cuts or procedures.
History of taking anticoagulants.
History of allergic reaction to lidocaine.
History of allergic reaction to tape, adhesive bandages, or dressings.
Inability to maintain the dressing for any reason.
Pregnancy or lactation.
Treatment with another investigational drug or other intervention within the past 30 days.
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).
History of reactions to mammalian meat, food allergies, urticaria or anaphylaxis.
History of venom allergy (bee, wasps).
History of drug allergies.
History of atopy asthma, atopic dermatitis, moderate to severe allergic rhinitis.
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.
Refusal to allow storage of samples and data for future usage..
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 capacity to consent:

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 lose the ability to consent during participation will be monitored for safety but will have no additional research procedures performed.