The Uninfected Ixodes Scapularis Human Tick Challenge Model (TICK ME)

An innovative way to prevent multiple tick-borne diseases is an anti-tick vaccine, i.e. targeting the vector to prevent transmission of pathogens from the tick to the host. The rationale for an anti-tick vaccine stems from a phenomenon coined tick immunity. This study aims to show proof of concept that humans indeed develop immunity to ticks. Therefore subjects will be challenged three to four times with ticks reared in colony from a designated laboratory and that are exhaustively tested negative for various known tick-borne pathogens. Several tick feeding parameters will be evaluated to assess the development of tick immunity in the subjects. To this end, a total amount of ten ticks per challenge will be placed under a dressing placed on the forearm. The primary study endpoint is the tick feeding phenotype. Secondary parameters are signs of an immune response in the host; itch, redness, or other signs of a (local) immune response (blood and skin biopsies). All parameters, except for the skin biopsies, will be collected/evaluated after each tick challenge.

Study Overview

• Status: Recruiting
• Conditions: Tick Bites; Tick Immunity
• Intervention / Treatment: Other: Ixodus scapularis nymphs

Detailed Description

This will be an, single centre, experimental study. The design of the study is similar to a human challenge trial, with the important exception that the subjects in this study are not experimentally infected with a pathogen, but are exposed to well-characterized laboratory-reared uninfected nymphal Ixodes scapularis ticks.

Seven healthy human volunteers of >18 years old who have no history of known tick-bites or tick-borne diseases will be recruited. Subjects will undergo three to four tick challenges, consisting of five to six days per challenge with two weeks between the consecutive challenges. The total duration of participation is approximately five months for each subject. By making use of ticks from a laboratory-reared tick colony that have been, and are being, used in xenodiagnosis and tick challenge models in the USA and that are well tolerated minimizing the risks of the tick challenges. Regardless, the tick challenge can cause some discomfort because of possible local reactions and because the dressing must be kept dry for five to six days. The risk of infection with a tick-borne pathogen is negligible due to the fact that these ticks are exhaustively tested for various known tick-borne pathogens. Finally, risks are considerated of development of a red meat allergy or other allergic reactions negligible because no clear associations are known of I. scapularis ticks and red meat allergy. No serious adverse events (such as human infections or red meat allergy) have resulted from more than >100 challenges in the United States using this tick colony. There are no direct benefits of participation.

• Study Type: Interventional
• Enrollment (Estimated): 7
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hannelore. JL Beaart, PhD; Phone Number: +31205667906; Email: tickme@amsterdamumc.nl
• Study Contact Backup: Name: Stefanie A Gauw, Coordinator; Phone Number: +31205667906; Email: tickme@amsterdamumc.nl

Study Locations

• Netherlands
  • Noord-Holland
    • Amsterdam-Zuidoost, Noord-Holland, Netherlands, 1105 AZ
      • Recruiting
      • AUMC Location AMC
      • Contact: H. Beaart, Msc; Phone Number: 0031207327170; Email: TICKME@amsterdamumc.nl

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age: 18 years and older;
• Negative Borrelia VlsE1/pepC10 ELISA.

Exclusion Criteria:

• Known history of tick bites;
• Positive Borrelia serology (VlsE1/PepC10 ELISA);
• Known history or current suspicion on any tick-borne disease;
• Chronic skin condition affecting the arm skin;
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental	Other: Ixodus scapularis nymphs; Tick challenge

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tick weight	Tick weight in mg	Up to 1 week
Tick feeding molting success	Molting success rate	Up to 1 week
Tick survival	tick survival rate	Up to 1 week
Tick attachment	tick attachment rate	Up to 1 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Signs of an immune response in the host: Itch	Itch	Up to 1 week
Signs of an immune response in the host: redness	Redness	Up to 1 week
Signs of an immune response in the host: other	Other signs of a local immune response (in blood)	3 weeks
Signs of an immune response in the host: biopsies	Other signs of a local immune response (in skin biopsies)	9 weeks

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Collaborators: ZonMw: The Netherlands Organisation for Health Research and Development

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2023
• Primary Completion (Estimated): July 1, 2024
• Study Completion (Estimated): July 1, 2024

Study Registration Dates

• First Submitted: March 28, 2023
• First Submitted That Met QC Criteria: July 19, 2023
• First Posted (Actual): July 28, 2023

Study Record Updates

• Last Update Posted (Actual): July 28, 2023
• Last Update Submitted That Met QC Criteria: July 19, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Tick bites; Ixodus scapularis; Tick Challenge model; Tick borne diseases; Tick immunity
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Wounds and Injuries; Poisoning; Bites and Stings; Tick Bites
• Other Study ID Numbers: NL81259.018.22

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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