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Safety of and Immune Response to a Tick-Borne Encephalitis Vaccine (LGT(TP21)/DEN4) in Healthy Adults

Phase 1
Completed
Conditions
Tick-Borne Encephalitis
Interventions
Biological: LGT(TP21)/DEN4
Biological: Placebo
Registration Number
NCT00118924
Lead Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Brief Summary

Tick-borne encephalitis (TBE) is a viral illness common in the Northern Hemisphere, especially Europe and Asia. TBE infection may lead to central nervous system problems and death. The purpose of this study is to test the safety of and immune response to a TBE vaccine in healthy adults. The vaccine is related to a live attenuated virus developed against dengue virus infection.

Detailed Description

TBE is a common illness in Europe and Asia, where it is usually associated with mild illness but sometimes leads to long-term symptoms and even death. This study will evaluate the safety and immunogenicity of a live attenuated chimeric virus, LGT(TP21)/DEN4, which is derived from the Langat flavivirus and DEN4 dengue virus serotypes.

Each volunteer will be involved in the study for 180 days. Participants in Cohort 1 will be randomly assigned to receive LGT(TP21)/DEN4 or placebo at study entry. Cohort 2 will begin only after safety review of all participants in Cohort 1. Participants in Cohort 2 will receive a higher dose of LGT(TP21)/DEN4 or placebo.

After vaccination, participants will be asked to monitor their temperatures every day for 16 days and on Day 19. Study visits will occur every other day after vaccination until Day 16, followed by 5 additional visits at selected days through Day 180. Blood collection and a targeted physical exam will occur at each study visit. Some participants will be asked to undergo a skin biopsy or additional blood collection at selected visits.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
28
Inclusion Criteria
  • Willing and available to be followed for the duration of the study
  • Willing to use acceptable means of contraception
  • Good general health
Exclusion Criteria
  • Pregnancy or breastfeeding
  • Clinically significant neurologic, heart, lung, liver, rheumatologic, autoimmune, or kidney disease
  • Behavioral, cognitive, or psychiatric disease that, in the opinion of the investigator, affects the ability of the volunteer to understand and cooperate with the study
  • Blood disease
  • History of migraine headaches
  • History of encephalitis
  • Alcohol or drug use that has caused medical, occupational, or family problems within 12 months prior to study entry
  • History of severe allergic reaction or anaphylaxis
  • Emergency room visit or hospitalization for severe asthma within 6 months prior to study entry
  • HIV-1 infected
  • Hepatitis C virus infected
  • Hepatitis B surface antigen positive
  • Known immunodeficiency syndrome
  • Use of corticosteroids or immunosuppressive drugs within 30 days prior to study entry. Participants who have used topical or nasal corticosteroids are not excluded.
  • Live vaccine within 4 weeks prior to study entry
  • Killed vaccine within 2 weeks prior to study entry
  • Blood products within 6 months prior to study entry
  • Investigational drug or vaccine within 3 months prior to study entry
  • Previously received a licensed or experimental yellow fever, tick-borne encephalitis, or dengue vaccine
  • Surgical removal of spleen
  • History of tick-borne encephalitis
  • History of dengue virus infection or other flavivirus infection (e.g., yellow fever virus, St. Louis encephalitis, West Nile virus, Japanese encephalitis virus)
  • Other condition that, in the opinion of the investigator, would affect the participant's participation in the study

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
1LGT(TP21)/DEN4One subcutaneous vaccination with a 10\^3 PFU dose of LGT(TP21)/DEN4 vaccine given in the deltoid region of either arm. A second booster vaccination will be given 6 months after the first vaccination.
2LGT(TP21)/DEN4One subcutaneous vaccination with a 10\^5 PFU dose of LGT(TP21)/DEN4 vaccine given in the deltoid region of either arm. A second booster vaccination will be given 6 months after the first vaccination. This arm may enroll after Arm 1 depending on the immunological response of Arm 1.
3PlaceboOne subcutaneous vaccination with a placebo vaccine given in the deltoid region of either arm. A second placebo vaccination will be given 6 months after the first vaccination.
Primary Outcome Measures
NameTimeMethod
Frequency of vaccine-related adverse effects, graded by intensity and severity through active and passive surveillanceThroughout study
Immunogenicity of vaccine against anti-Langat neutralizing antibodyAt Days 0, 28, 42, and 180
Secondary Outcome Measures
NameTimeMethod
Recovery of virus from the blood of a vaccinee or seroconversionThroughout study
Immunogenicity of the LGT(TP21)/DEN4 vaccine against other TBE virusesThroughout study
Durability of antibody responses to Langat and other TBE virusesAt Day 180

Trial Locations

Locations (1)

Vanderbilt University School of Medicine

🇺🇸

Nashville, Tennessee, United States

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