Immune Responses After Human Subject Challenge With Sand Fly Bites

Immune Responses After Human Subject Challenge With Sand Fly Bites: Exploratory Study for Selection of Potential Leishmania Vaccine Antigen Candidates

Sand flies can carry the infection leishmaniasis (a parasite). The purpose of this study is to evaluate the human immune response to uninfected laboratory raised sand fly bites and select from the immune response to sand fly saliva, possible substances to use for a future vaccine to protect against the parasite leishmaniasis.

Study Overview

• Status: Completed
• Conditions: Healthy

Detailed Description

Based on travel history and possible exposure, subjects were entered into one of 2 arms, Ph. dubosqui or Lu. lutzomyia controlled sand fly repeated feedings. At baseline a pheresis was done to collect baseline cells. Subjects received sand fly bites on a q2 week schedule for 2 months followed by a q2 months schedule for one year. They had an option to extend for a late recall feeding at 18 months, when a skin biopsy was performed 48 hours after sand fly bites. Currently the study is fully enrolled and all human subject contact is complete. We (laboratory at NIAID) are studying the humoral, cellular immune responses using blood samples, and cytokine expression in the skin biopsy samples.

• Study Type: Observational
• Enrollment (Actual): 68

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20814
      • Walter Reed National Military Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Male and female military health care beneficiaries in good health, age 18-50

Description

Inclusion Criteria:

• Age 18-50
• Plans to remain in DC area for at least one year
• willingness to participate in all study procedures
• general good health
• military health care beneficiary
• able to provide informed consent

Exclusion Criteria:

• Prior travel to geographic areas where leishmania transmitting sand flies are common
• positive antibody to sand fly saliva on screening blood test
• pregnancy
• elevated serum IgE
• history of chronic medical illness
• adult history of treatment requiring anemia
• large reactions to insect bites
• history of multiple vasovagal reactions to phlebotomy
• difficult venous access for phlebotomy
• Taking medications that could interfere with immune responses

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Phlebotomus group; Those in the Phlebotomus group will have exposure to P. duboscqui sand fly
Lutzomyia group; Those placed in this group will receive exposure to L. longipalpis sand fly bites.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Human Th1 immune response to specific sand fly salivary proteins	Subject blood will be obtained at set points after repeated controlled sand fly feedings, duration for 20 minutes. Sand fly salivary molecules that demonstrate a strong Th1 immune response in these human PBMC, and little Th2 cytokine induction will be considered for development as future leishmania vaccine antigen candidates.	6-18 months

Collaborators and Investigators

• Sponsor: Uniformed Services University of the Health Sciences
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Principal Investigator: Naomi E Aronson, MD, Uniformed Services University of the Health Sciences

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (ACTUAL): April 1, 2016
• Study Completion (ACTUAL): April 15, 2016

Study Registration Dates

• First Submitted: February 3, 2011
• First Submitted That Met QC Criteria: February 3, 2011
• First Posted (ESTIMATE): February 4, 2011

Study Record Updates

• Last Update Posted (ACTUAL): February 19, 2018
• Last Update Submitted That Met QC Criteria: February 15, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: leishmaniasis; immune response; Sandfly; individuals age 18-50
• Other Study ID Numbers: G183ZU; Y1-AI-0744-01 (OTHER_GRANT: NIAID Interagency Agreement)