Expanded Dryvax Dilution Study in Previously Vaccinated Adults
Condition: Smallpox
MeSH terms: Smallpox
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to determine the safety and effect of diluting smallpox vaccine,
      making a larger number of doses in case smallpox is released into the environment. A total of
      up to 927 healthy adults between the ages of 32 and 70 years who were already vaccinated
      against smallpox (but not since 1989) will volunteer for this study for up to 34 weeks and
      receive different strengths of vaccine. Some subjects may participate for longer if they
      choose to be revaccinated because the first vaccination does not take. The vaccine will be
      given by making small cuts in the skin and putting the vaccine into these cuts. After the
      screening visit, volunteers will be followed through study visits and follow up phone calls.
      Blood will be collected during some study visits to look at the immune system (body system
      that fights infection) response.
    

Detailed description: 
      The purposes of this multi-center, double blind randomized dose response study are: to
      evaluate the safety of undiluted Dryvax and Dryvax diluted at 1:5 and 1:10 in adults between
      the ages of 32 and 70 years who were previously vaccinated but not since 1989 and to define,
      with very high precision (+/-3%), the proportion of individuals who respond with a "take" 6
      to 11 days after vaccination with undiluted Dryvax vaccine and Dryvax diluted at 1:5. A
      "take" is defined as the formation of a lesion at the site of vaccination that is consistent
      with the description of a successful vaccination described in the IB Secondary study
      objectives include defining with good precision (+/- 10%), the proportion of individuals who
      respond with a "take" 6 to 11 days after vaccination with a 1:10 dilution of Dryvax vaccine
      and exploring correlations between "takes"/ no-"take" and immune responses in all vaccine
      groups (antibody responses in all volunteers; and assays of cell-mediated immunity in a
      convenience sample consisting of 15 volunteers enrolled at each site (total N = 105) randomly
      distributed across the vaccine groups). Immunogenicity assays will include neutralizing
      antibody to vaccinia, vaccinia binding antibody, ELISPOT for gamma interferon [Assays of
      cell-mediated immunity will be performed only on a convenience sample consisting of 15
      volunteers enrolled at each site (total N = 105)] and intracellular cytokine production.
      Primary safety endpoints include safety data regarding the three doses of vaccine in
      previously vaccinated subjects as assessed by adverse events reported by the subjects and/or
      investigators and changes observed during the scheduled clinic visits. Specific attention
      will be paid to the following: local reactogenicity at the site of injection: pain,
      tenderness, erythema, induration, regional lymphadenopathy, limitation of limb movement;
      systemic symptoms: fever, myalgia, fatigue, and headache; anaphylaxis, and hypersensitivity
      reactions; other reactions: dermatologic, neurologic, gastrointestinal (nausea/vomiting,
      diarrhea). The primary efficacy endpoint for this trial will be the proportion of vaccinees
      demonstrating a "take" 6 to 11 days after the first vaccination at each of the dose levels
      (undiluted and 1:5 and 1:10). Secondary endpoints are: immune responses as assessed by
      vaccinia neutralizing antibody measured on all subjects and binding antibody to vaccinia on
      all subjects and the size of the lesions observed in all subjects compared across the
      dilution groups. Tertiary endpoints of 15 volunteers at each site randomly distributed across
      the vaccine groups are cellular immune responses as assessed by: ELISPOT for gamma interferon
      in response to vaccinia antigens and intracellular cytokine production.
    

Intervention name(s): Live vaccinia virus vaccine; Live vaccinia virus vaccine
Intervention type(s): Biological; Biological
Intervention description(s): Dryvax undiluted. Cohort A receives undiluted dose of Dryvax vaccine; Dryvax with diluent (50% glycerin and 0.25% phenol in sterile water). Cohort A-C receives diluted dose of Dryvax vaccine.
Intervention MeSH terms: Vaccines
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: smallpox, Dryvax, vaccine, dilution