Acquired Tick Resistance in Naturally Exposed Participants (TICK REACT)

The Uninfected Ixodes Scapularis Human Tick Challenge Model - Acquired Tick Resistance in Naturally Exposed Participants

Tick-borne diseases are increasing worldwide, and there are currently few effective ways to prevent them. One promising new strategy is to develop a vaccine that targets the tick itself ("anti-tick vaccine") to block the transmission of multiple pathogens. Some animals naturally develop resistance to ticks after repeated tick bites. There are indications that a similar form of acquired tick resistance (ATR) may also occur in humans who have been heavily exposed to ticks. This study investigates whether humans can naturally develop tick resistance and how this affects tick feeding. The investigators will compare people with a long history of tick bites and self-reported signs of tick resistance to people who are tick-naïve. The investigators will also include a small group of volunteers who previously participated in an experimental human tick challenge to evaluate what their reaction on tickbites is 1-2 years after their initial exposures.

Study Overview

• Status: Active, not recruiting
• Conditions: Tick Bites; Tick Resistance
• Intervention / Treatment: Other: Tick challenge

Detailed Description

Study Objectives Primary Objective To determine whether humans develop naturally acquired tick resistance by measuring tick feeding success, specifically the weight of ticks after feeding.

Secondary Objectives To measure additional tick feeding parameters (tick mortality, attachment rate, duration of feeding, and molting).

To assess clinical skin reactions such as itch and redness. To study immune responses (antibodies and immune cells) against tick saliva proteins in all groups.

To identify tick salivary antigens that may be useful for future anti-tick vaccine development.

Study Design Single-center, open-label human experimental tick challenge study.

Three groups:

ATR group: 11 adults with extensive prior tick exposure and self-reported signs of tick resistance.

Control group: 11 adults with no significant tick exposure. Follow-up challenge group: Up to 4 adults previously challenged in the "TICK ME" study.

Outcome measures Primary Outcome Measure Post-feeding tick weight

Secondary Outcome Measures Tick mortality, attachment rate, days attached, and molting success Clinical skin responses (itch, redness) Immune responses to tick salivary proteins Skin biopsy analyses

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • North Holland
    • Amsterdam, North Holland, Netherlands, 1105AZ
      • Amsterdam UMC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Naturally acquired self-reported tick resistant individuals:

• Age: 18 - 70 years;
• History of repeated tick bites
• Local reaction (like redness or itch) at place of previous tick bites and/or signs of impaired tick feeding after bite (anamnestic)

Controls:

• Age: 18 years - 70 years;

Experimentally acquired tick resistant individuals:

• Previous participant in the TICK ME study that has completed all 4 challenges
• Age: 18 years - 70 years;

Exclusion Criteria:

• Current suspicion of any tick-borne disease
• Diagnosed with tick-borne disease within the last year
• Chronic skin condition affecting the skin of the arm;
• Inability to maintain the dressing for any reason;
• Known immunodeficiency or autoimmune disease;
• Use of systemic immunomodulating drugs or chemotherapy, current or in the past;
• Chronic use of antibiotics;
• Unable to give informed consent or do not have a thorough command of the Dutch language;
• Refusal to participate in specimen collection and storage for future study related use;
• Pregnant or breastfeeding women;
• Not willing to use adequate contraception during the study period;
• Red meat allergy (both medically confirmed and self-reported);
• Use of investigational therapy and devices during the time of the study;
• Any other condition that, in the opinion of the investigator, would make the patient unsuitable for enrolment or could interfere with the patient participating in and completing the study.

Additional exclusion criteria for controls:

• Known history of tick bites;
• Positive Borrelia serology (VlsE1/PepC10 ELISA);
• Known history or current suspicion on any tick-borne disease

Additional exclusion criteria for experimentally acquired tick resistant individuals:

• History of tick bites acquired outside of TICK ME study;
• Positive Borrelia serology (VlsE1/PepC10 ELISA);
• Known history or current suspicion on any tick-borne disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tick naive individuals; Individuals who have never been bitten by ticks before (as far as known)	Other: Tick challenge; uninfected ixodes scapularis ticks will be placed underneath a closed dressing
Experimental: Supposed tick immune individuals; Individuals who have been bitten by a lot of ticks before and experience a local reaction after each tickbite.	Other: Tick challenge; uninfected ixodes scapularis ticks will be placed underneath a closed dressing
Experimental: Previous TICK ME participants; Individuals who have participated in the TICK ME study	Other: Tick challenge; uninfected ixodes scapularis ticks will be placed underneath a closed dressing

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tick feeding: tick weight	Tick weight measured in mg after complete feeding of the tick	From the start of the tick challenge until feeding to repletion of the ticks (max 10 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tick feeding: tick mortality	Tick mortality in % of fed ticks	From the start of the tick challenge until feeding to repletion of the ticks (max 10 days)
Host reaction: redness	Redness (using a standardized clinical erythema (CEA) score (scale 0-4) which is scored by physicians using photographs of tick bite lesions)	Redness will be monitored at day 2 and the last day of the tick challenge
Host reaction: itch	Itch (using Visual Analogue Scale 0-100) as a sign of a clinical reaction of the host	Itch is measures daily during the tick challenge (From the start of the tick challenge until feeding to repletion of the ticks (max 10 days)
Host immune response: humoral	Humoral (qualitative by characterizing antibodies recognizing anti-tick antigens using a yeast surface display expressing tick salivary gland proteins)	From the start of the challenge, day 2, day 5, final day of challenge (day 5-10) depending upon tick feeding, 3-5 weeks after the challenge and 10-12 weeks after the challenge
Host immune response: cellular	Cellular (immunophenotyping of the different immune subsets in collected PBMCs at the specified time points) of immune responses in blood	From the start of the challenge, day 2, day 5, final day of challenge (day 5-10) depending upon tick feeding, 3-5 weeks after the challenge and 10-12 weeks after the challenge

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Investigators: Principal Investigator: Joppe W Hovius, Prof. Dr., Amsterdam UMC

Study record dates

Study Major Dates

• Study Start (Actual): August 14, 2025
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: December 3, 2025
• First Submitted That Met QC Criteria: March 15, 2026
• First Posted (Actual): March 18, 2026

Study Record Updates

• Last Update Posted (Actual): March 18, 2026
• Last Update Submitted That Met QC Criteria: March 15, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Tick resistance in naturally exposed individuals; tick resistance in tick-naive individuals
• Additional Relevant MeSH Terms: Wounds and Injuries; Chemically-Induced Disorders; Poisoning; Bites and Stings; Tick Bites
• Other Study ID Numbers: NL-009527

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: The descision about sharing the IPD will follow

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No