Clinical Trial of the BioMed rTSST-1 Variant Vaccine in Healthy Adults
Condition: Toxic Shock Syndrome
MeSH terms: Shock, Septic; Shock
Intervention: rTSST-1v
Intervention description: Each subject of a total of seven groups will receive three injections (first injection day 0; second injection 3 months ± 4 weeks after the first, third injection 6 months ± 4 weeks after the second) of one of two different doses of Vaccine or Adjuvant, each group comprising 20 subjects. Subjects will be controlled 24 h post vaccination. Follow-up will last 18 months on the average, with visits every three months (± 2 weeks). Response to treatment is defined by seroconversion from a TSST-1 binding Ab titer of < 20 to > 40 or a 4-fold increase in TSST-1 binding Ab titer .
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Sequential Assignment
Intervention model description: Two different doses of rTSST-1 Variant Vaccine were tested in different administrational schedules. These were: a comparison of 10µg versus 100µg rTSST-1 Variant Vaccine administered one, two, or three times.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 140.0
Sex: All
Minimum age: 18 Years
Maximum age: 64 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Sepsis; Vaccination

Summary:

      Toxic Shock Syndrome (TSS) is a severe condition with high morbidity and mortality from the
      hosts overwhelming inflammatory response and cytokine storm. Staphylococcal superantigen
      toxins are the main causative agents. Toxic shock syndrome toxin (TSST-1) being responsible
      for almost all of menstruation associated and more than 50% of all other cases. There is no
      specific therapy.

      The aim of this study is to extend the safety and tolerability of two doses of the BioMed
      recombinant toxic shock syndrome toxin (rTSST-1) Variant Vaccine after one to three
      vaccinations in healthy adults. The second aim of the study is to measure immunogenicity and
      persistence of antibodies which produced in response to treatment with the BioMed rTSST-1
      Variant Vaccine over a period of 12 months. These antibodies are expected to be important in
      prevention and mitigation of the diseases. 140 healthy adults, male and female, age 18-64
      years will be assigned to 7 groups comprising two doses of the vaccine or adjuvant at the
      Department of Clinical Pharmacology of the Medical University of Vienna. The patients will be
      monitored for vital signs, hematology, clinical chemistry, and antibodies against TSST-1.
      Immunization will be repeated 3 months after the first with the same dose and 6 months after
      the second immunization in the respective groups.

      Antibodies will be determined through monitoring TSST-1 binding antibodies as assessed
      through ELISA and neutralizing antibodies (exploratory endpoint) as assessed by inhibition of
      T cell activation (3H Thymidine incorporation; ≥ 50%).
    

Eligibility criteria:

        Inclusion Criteria:

          -  males or females aged 18-64 years

          -  signed informed consent

          -  physical exam: no abnormal findings unless considered irrelevant by the investigator

          -  uneventful medical history

          -  Females with childbearing potential: adequate contraception

        Exclusion Criteria:

          -  females with childbearing potential: pregnancy, lactation or unreliable contraception

          -  positive HIV Ab and/or positive HCV Ab and/or positive HBsAG signs and symptoms of
             autoimmunity

          -  TSST-1 Ab titer > 1:1000

          -  current or recent (< 1 month) immunosuppressive therapy with corticosteroids or
             immunomodulators