Safety and Tolerability Study of the VAC∆6 Vaccine in Volunteers Aged 18-40 Years
Condition: Smallpox; Monkeypox; Cowpox; Vaccinia Virus Infection
MeSH terms: Infections; Vaccinia; Smallpox; Monkeypox
Study type: Interventional
Phase: Phase 1

Summary: 
      The aim of the clinical study is to study the safety and tolerability of the live cell-based
      vaccine against smallpox and other orthopoxvirus infections (VAC∆6 vaccine) based on vaccinia
      virus, in intracutaneous administration.

      The research tasks are to:

        -  evaluate the safety of various schemes for the use of the VAC∆6 vaccine using a set of
           clinical and laboratory-instrumental methods (thermometry, blood pressure registration,
           auscultation of the heart and lungs, electrocardiography (ECG), complete blood count and
           common urine test, biochemical, immunological, and virological studies);

        -  evaluate the reactogenicity of various schemes for the use of the VAC∆6 vaccine (taking
           into account the number of local and systemic reactions, the percentage of those
           vaccinated with various degrees of manifestation of systemic and local reactions);

        -  evaluate the possibility of virus shedding into the environment by volunteers;

        -  evaluate the immunological efficacy of various vaccine administration schemes;

        -  identify the development of undesirable reactions to the administration of the vaccine;

        -  evaluate the cellular immune response to the introduction of various schemes for the use
           of the vaccine;

        -  evaluate preliminary efficacy data in order to select an optimal scheme for the
           administration of the vaccine to make a decision on conducting Phase II clinical trials
           in an extended group of volunteers.
    

Detailed description: 
      This study is an open-label, controlled, parallel-group clinical trial. The study included 60
      healthy volunteers of both sexes aged 18-40 years who had not been vaccinated against
      smallpox, had no vaccine marks and anti-smallpox virus neutralizing antibodies in their sera
      as well as those who met the inclusion criteria and did not have any exclusion criteria.

      Distribution of volunteers by groups:

      Group 1: 15 volunteers vaccinated once intradermally at a dose of 10⁶ plaque-forming units
      (PFU) (0.2 ml) of the VAC∆6 vaccine in the outer surface of the shoulder 8-10 cm below the
      shoulder joint; Group 2: 15 volunteers vaccinated once intradermally at a dose of 10⁷ PFU
      (0.2 ml) of the VAC∆6 vaccine in the outer surface of the shoulder 8-10 cm below the shoulder
      joint; Group 3: 15 volunteers vaccinated twice spaced 28 days apart, intradermally at a dose
      of 10⁶ PFU (0.2 ml) of the VAC∆6 vaccine in the outer surface of the shoulder 8-10 cm below
      the shoulder joint; Group 4: 15 volunteers vaccinated by the two-step vaccination method:
      Step 1 - the first vaccination once subcutaneously with 1 dose (0.5 ml) of the inactivated
      smallpox vaccine OspaVir® in the area of the left shoulder 8-10 cm below the shoulder joint;
      Step 2 - the second vaccination once by the method of multiple puncture into the outer
      surface of the shoulder 8-10 cm below the shoulder joint with a live smallpox vaccine at a
      dose of 1x 10⁶ PFU 7 days following the first vaccination with OspaVir®.

      Since the product "Live cell-based vaccine against smallpox and other orthopoxvirus
      infections (VAC∆6 vaccine) based on vaccinia virus" was used for the first time for human
      vaccination, the vaccination of volunteers was started at a low dose, i.e. 1x10⁶ PFU.

      The first five volunteers included in Group 1 were vaccinated intradermally at a dose of
      1x10⁶ PFU. The volunteers were monitored daily; 14 days after vaccination, in the absence of
      side effects and after the results were agreed upon, vaccination was performed for the
      remaining 10 Group 1 volunteers and the first 5 volunteers of Group 2 who were vaccinated at
      a dose of 1x10⁷ PFU. After 14 days, in the absence of adverse effects (AEs) or serious
      adverse effects (SAEs), the rest of the volunteers included in Group 2 were vaccinated.

      After receiving the results indicating the absence of AEs or SAEs in the volunteers
      vaccinated once with the VAC∆6 vaccine at a dose of 1x10⁶ PFU, the first vaccination of Group
      3 volunteers was performed, the dose of the vaccine was 1x10⁶ PFU, and after 28 days - the
      second vaccination was performed.

      Group 4 was vaccinated with reference products: live smallpox vaccine (smallpox vaccine) and
      the OspaVir® vaccine, an inactivated smallpox vaccine.

      Vaccination was performed in two steps:

        -  the first step: subcutaneous administration of the inactivated smallpox vaccine
           OspaVir®;

        -  the second step: skin inoculation with a live smallpox vaccine.
    

Intervention name(s): VAC∆6 vaccine - оnce at a dose of 10⁶ PFU; VAC∆6 vaccine - once at a dose of 10⁷ PFU; VAC∆6 vaccine - twice at a dose of 10⁶ PFU; Live smallpox vaccine (Smallpox vaccine) + The OspaVir® inactivated smallpox vaccine
Intervention type(s): Biological; Biological; Biological; Biological
Intervention description(s): 15 volunteers vaccinated once intradermally at a dose of 10⁶ PFU (0.2 ml) of the VAC∆6 vaccine in the outer surface of the shoulder 8-10 cm below the shoulder joint; 15 volunteers vaccinated once intradermally at a dose of 10⁷ PFU (0.2 ml) of the VAC∆6 vaccine in the outer surface of the shoulder 8-10 cm below the shoulder joint; 15 volunteers vaccinated twice spaced 28 days apart, intradermally at a dose of 10⁶ PFU (0.2 ml) of the VAC∆6 vaccine in the outer surface of the shoulder 8-10 cm below the shoulder joint; 15 volunteers vaccinated by the two-step vaccination method: Step 1 - the first vaccination once subcutaneously with 1 dose (0.5 ml) of the inactivated smallpox vaccine OspaVir® in the area of the left shoulder 8-10 cm below the shoulder joint; Step 2 - the second vaccination once by the method of multiple puncture into the outer surface of the shoulder 8-10 cm below the shoulder joint with a live smallpox vaccine at a dose of 1x 106 PFU 7 days following the first vaccination with OspaVir®.
Intervention MeSH terms: Vaccines
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This study is an open-label, controlled, parallel-group clinical trial.
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: VAC∆6 vaccine; Smallpox; Оrthopoxviruses; Сlinical study