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A Phase II, Open Label Trial of a Vaccine (FSME-IMMUN 0.5 mL) Against Tick-borne Encephalitis (TBE) for NIAID Workers Manipulating Tick Borne Encephalitis Virus (TBEV) in the Laboratory

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ClinicalTrials.gov Identifier: NCT01031537
Recruitment Status : Terminated
First Posted : December 14, 2009
Last Update Posted : October 6, 2017
Information provided by (Responsible Party):

Study Description
Brief Summary:


  • Infection by tick-borne encephalitis virus (TBEV) is a significant health concern for humans in Europe and Asia. A vaccine is available in these regions and in Canada, but not in the United States. Research studies in Europe have shown the vaccine to be effective in preventing infection among the general population, where disease is transmitted either by the bite of an infected tick (most common) or by ingestion of contaminated unpasteurized milk or milk products. Persons who work with the virus in a research setting, however, have the potential of being exposed in unnatural ways, and may come into contact with concentrations of virus higher than those found naturally in ticks.
  • The Food and Drug Administration is investigating the effectiveness of the existing vaccine. It is a killed vaccine, which means that it has been treated to ensure that it does not contain live agents (bacteria or virus). The manufacturer has tested the product for other possible contaminating agents and none have been detected. However, there is an unknown but small risk of exposure to undetected contaminating agents in the vaccine.


  • To test the safety and immune response to a vaccine against tick-borne encephalitis virus (TBEV).
  • To add a level of protection to persons who may have occupational exposure to TBEV to reduce their chances of developing infection from that exposure.


- Individuals 18 years of age or older who are in generally good health and have the potential for occupational exposure to TBEV at one of the two National Institute of Allergy and Infectious Diseases campuses.


  • Subjects receiving the full series of the vaccine will receive at least three doses by injection in the upper arm. The first and third dose of study vaccine will be given in the muscle of the nondominant arm. The second dose will be given in the dominant arm.
  • Participation will include at least 12 scheduled visits to the study center over approximately 3.5 years.
  • An initial visit will take place 7 to 21 days prior to the first injection. Blood samples will be taken to test liver and kidney function, baseline antibody levels, and for possible pregnancy in female participants.
  • Doses will be given on days 0, 14, and 161. Participants will be asked to complete a diary card on each day for one week following the vaccination to assess any reactions or side effects. At each visit after receipt of a vaccine, participants will be asked about any side effects.
  • Blood will be drawn 14 days after the second injection and 21 days after the third injection in order to measure the level of antibodies and overall response to the vaccine.
  • Subjects who develop a sufficiently high level of antibodies may (at the discretion of the laboratory chief) be allowed to work with strains of TBEV at Biosafety Level (BSL) 3 rather than BSL-4. Blood will be drawn annually for 3 years to determine antibody level and response to the vaccine. Booster doses will be provided if required.

Condition or disease Intervention/treatment Phase
Tick-Borne Encephalitis Encephalitis, Tick-Borne Tick-Borne Disease Glycoprotein E, Flavivirus NSI Protein, Flavivirus Biological: FSME-IMMUN 0.5ml Baxter Phase 2

Detailed Description:

This is an open label trial of a non-US licensed vaccine for tick-borne encephalitis. The vaccine has been licensed by Baxter, now following an acquisition by Pfizer Inc in Vienna, Austria since 2001, and has an extensive safety record in multiple European countries. Field effectiveness studies suggest > 99 percent protection against disease transmitted by the natural routes of either tick bite or ingestion of contaminated, unpasteurized milk. The vaccine is also considered to be effective against laboratory exposures and is used routinely for this purpose in European laboratories. The US Centers for Disease Control and Prevention and the National Institutes of Health acknowledge the effectiveness of the vaccine by allowing those who have received it to study tick-borne encephalitis virus (TBEV) in isolation facilities rated at BSL-3 rather than the more stringent BSL-4, with the exception of the Russian Spring-Summer Encephalitis strain.

Subjects will be personnel from 2 intramural campuses of the National Institute of Allergy and Infectious Diseases who may be exposed accidentally to any strain or serotype of viable TBEV. Approximately 160 individuals are eligible to participate. Inclusion and exclusion criteria are defined. The rapid immunization schedule (injections on Days 0, 14, and 161) will be used and subjects will have labs drawn 21 days after the 2nd, 3rd and 4th vaccine injections to determine seroconversion. Subjects who seroconvert to TBEV will be offered a booster dose of the vaccine 3 years from the date of receipt of the third dose of the vaccine. Subjects who are seropositive at entry into the study will be offered a booster dose of the vaccine every 3 years from Day 0.

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 26 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: A Phase II, Open Label Trial of a Vaccine (FSME-IMMUN 0.5 mL) Against Tick-Borne Encephalitis (TBE) for NIAID Workers Manipulating Tick-Borne Encephalitis Virus (TBEV) in the Laboratory
Study Start Date : September 25, 2009
Primary Completion Date : December 23, 2016
Study Completion Date : December 23, 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Encephalitis
U.S. FDA Resources

Arms and Interventions

Intervention Details:
    Biological: FSME-IMMUN 0.5ml Baxter

Outcome Measures

Primary Outcome Measures :
  1. Determine the rate of development of both a level of anti-tick borne encephalitis antibody and viral neutralization titer that have been found to protect against TBEV infection after 3 doses of IM FSME-Immun. [ Time Frame: 6 months ]

Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years to 100 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

All subjects must meet the following criteria at study entry:

  • Be engaged in activities that place them at potential risk of occupational exposure to TBEV in its viable form at one of the participating intramural laboratories of NIAID
  • Be 18 years of age or older at the time of the first immunization.
  • Comprehend the study requirements.
  • Provide written informed consent to participate in this study.
  • Be in good health as determined by the Investigator, based upon medical history and a targeted physical examination.
  • Have a stable health status as determined by the Investigator.
  • Have access to a consistent means of telephone contact, which may be either in the home or at the workplace, land line or mobile, but NOT a pay phone or other multiple-user device (i.e., a common use phone serving multiple rooms or apartments).
  • Express availability for the required study period, and ability to attend scheduled visits.


The following criteria should be checked at the time of the study entry. If any apply, the subject will not be included in the study:

  • The subject must not be participating in any other trial of an investigational drug or vaccine for 1 month prior to the first injection through until 21 days after the third injection. (Given the nature of the work these study subjects engage in, exemptions to this proscription may be granted on a case by case basis after discussion between the Investigator and the IRB.)
  • The presence on the day of immunization of an oral temperature of >101.2 degrees F or acute symptoms other than mild severity.
  • Active systemic infectious process as determined by review of systems and physical examination. The subject may be enrolled at a later date once the illness has resolved.
  • Known immune suppression, such as that associated with human immunodeficiency virus infection, or other condition, to the extent that, in the opinion of the Investigator, the subject is likely to have a poor response to the vaccine. This information will be obtained by history only. Serologic screening for these diseases will not be performed.
  • Presence of evidence of substance abuse or of neurological or psychiatric diagnoses which, even if clinically stable, are deemed by the Investigator to render the potential subject unable/unlikely to report promptly any adverse reactions to the vaccine.
  • Current diagnosis of leukemia, Hodgkin s disease, non-Hodgkin s lymphoma, or any other cancer, autoimmune disease such as lupus, which is in and of itself a cause of immunosuppression to the point that, in the opinion of the Investigator, the subject is likely to have a poor response to the vaccine.
  • Currently receiving systemic immunosuppressive chemotherapy or immunotherapy (including glucocorticoids) resulting in immune suppression to the point that, in the opinion of the Investigator, the subject is likely to have a poor response to the vaccine.
  • Any neurological condition in which (in the opinion of the Investigator) the integrity of the blood brain barrier may have been compromised.
  • Licensed vaccines are not exclusionary but should be given at least 14 days before or after immunization (applies to each of the 3 scheduled TBEV injections) for inactivated vaccines and 30 days before or after immunization with any live vaccines. This is in order to avoid potential confusion of adverse reactions. (Given the nature of the work these study subjects engage in, exemptions to this proscription may be granted on a case-by-case basis after discussion between the Investigator and the IRB.).
  • Previous anaphylactic reaction to any TBE vaccine.

Known or suspected anaphylactic reaction to any constituent of FSME IMMUN, to include formaldehyde, protamine sulfate, gentamicin and neomycin, or current egg allergy.

  • Known pregnancy, or anticipating becoming pregnant in the first 8 months of the study or a positive urine beta-human chorionic gonadotropin (beta hCG) test result prior to immunization. If subjects become pregnant at some point in time after the 1st injection, no further injections will be given until after the pregnancy is completed, they are no longer nursing or have a negative beta-hCG result.
  • Lactating or nursing.
  • Women of child bearing potential (defined as pre-menopausal who have not undergone either hysterectomy or tubal ligation) who lack a history of reliable contraceptive practices. Reliable contraceptive practices (for the first 8 months of the study and within 21 days prior to or 42 days after booster immunizations) include:

    • Consistent abstinence from heterosexual activity
    • Consistent use of combined or progestogen oral contraceptives
    • Injectable progestogen
    • Implants of levonorgestrel
    • Estrogen or estrogen/progestogen vaginal ring
    • Percutaneous contraceptive patches
    • Intrauterine device (IUD) or intrauterine system (IUS)
    • Successful vasectomy of the sole male partner, or
    • Double barrier method (condom or occlusive cap plus spermicidal agent)
  • A history of a prior infection with TBEV or previously receiving a TBE vaccine will not be considered as an exclusionary criterion for immunization through this protocol. However, these subjects antibody titer data will not be included in the statistical analysis.
  • Any other conditions, which in the Investigator s judgment, might result in an increased risk to the subject, or would affect their participation in the study. Additionally the Investigator has the ability to exclude a subject if for any reason he/she feels the subject is not a good candidate for the study or will not be able to follow study procedures.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01031537

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
United States, Montana
Rocky Mountain Laboratory (RML)
Hamilton, Montana, United States, 59840
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Principal Investigator: James M Schmitt, M.D. National Institutes of Health Clinical Center (CC)
More Information

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01031537     History of Changes
Other Study ID Numbers: 090246
First Posted: December 14, 2009    Key Record Dates
Last Update Posted: October 6, 2017
Last Verified: December 23, 2016

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) ):
TBE Researcher
Anti-TBEV Levels
Tic-Borne Encephalitis

Additional relevant MeSH terms:
Encephalitis, Tick-Borne
Tick-Borne Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Encephalitis, Arbovirus
Arbovirus Infections
Virus Diseases
Encephalitis, Viral
Central Nervous System Viral Diseases
RNA Virus Infections
Flavivirus Infections
Flaviviridae Infections
Infectious Encephalitis
Central Nervous System Infections
Gram-Negative Bacterial Infections
Bacterial Infections
Protozoan Infections
Parasitic Diseases
Immunologic Factors
Physiological Effects of Drugs