Vaccine Study for Tick-Borne Encephalitis Virus (TBEV)
Condition: Tick-Borne Encephalitis; Encephalitis, Tick-Borne; Tick-Borne Disease; Glycoprotein E, Flavivirus; NSI Protein, Flavivirus
MeSH terms: Encephalitis, Tick-Borne; Tick-Borne Diseases; Encephalitis
Intervention: FSME-IMMUN 0.5ml Baxter
Intervention description: Vaccine
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 69.0
Sex: All
Minimum age: 18 Years
Maximum age: 100 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: FSME-Immun; TBEV; TBE Researcher; Plavivirus; Anti-TBEV Levels; Tic-Borne Encephalitis

Summary:

      This was an open label trial of a non-US licensed vaccine for tick-borne encephalitis. The
      vaccine was licensed by Baxter, and 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 were recruited from personnel at 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
      were eligible to participate. The rapid immunization schedule (injections on Days 0, 14, and
      161) was used and subjects had labs drawn 21 days after the 2nd, 3rd and 4th vaccine
      injections to determine seroconversion. Subjects that seroconverted to TBEV were offered a
      booster dose of the vaccine 3 years from the date of receipt of the third dose of the
      vaccine. Subjects that were seropositive at entry into the study were offered a booster dose
      of the vaccine every 3 years from Day 0.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        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.

        EXCLUSION CRITERIA:

        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.