Safety and Tolerability Study of the VAC∆6 Vaccine in Volunteers Aged 18-40 Years

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.

Inclusion Criteria:Consent to participate in the study after written informing.Healthy volunteers (men and women) aged 18 to 40:absence of somatic or infectious diseases during the last 6 months;body weight of volunteers should not go beyond 20% of the ideal body weight for a given sex, age, and height;absence during the last 6 months of antiviral therapy, the use of steroids (except for the local use of steroids in the form of ointments, eye drops, sprays or inhalations), immunomodulatory dugs;persons not infected with HIV, viral hepatitis B and C, lues;clinical and laboratory parameters within the range as follows: leukocytes: from 4,000 to 10,000 cells/mm³; platelets: 180,000 to 320,000 per mm³.Exclusion Criteria:Hypersensitivity to any component of the product, allergy to vaccine components.Pregnancy or breastfeeding.The military.Persons in custody in detention facilities and those serving sentences in correctional facilities.Children under the age of 18.Acute infectious or non-infectious diseases, exacerbation of chronic diseases less than 4 weeks prior to the study.Tuberculosis (pulmonary and extrapulmonary).Skin diseases: a) common dermatoses (pemphigus, psoriasis, eczema, atopic dermatitis), including those in the past; other acute and chronic diseases or impaired skin cover (burns, impetigo, herpes, herpes zoster chicken pox, pustular diseases).Immunosuppressive conditions: congenital or acquired immunodeficiency syndrome (including HIV infection), leukemia, malignant neoplasms, organ transplantation, cellular and humoral immunodeficiencies.Immunosuppressive therapy: treatment with antimetabolites, high doses of corticosteroids for 14 days or more, radio and x-ray therapy, etc.Cardiovascular diseases: decompensated heart defects, subacute bacterial endocarditis, myocarditis, pericarditis, hypertension of II-III degrees, angina pectoris, myocardial infarction; other forms of pathology: hypertension of the 1st degree, well-controlled heart defects, angina pectoris (mild forms).Diseases of the kidneys and urinary tract: diffuse glomerulonephritis, congenital nephropathy, chronic renal failure, pyelonephritis, toxic nephropathy (transient).Diseases of the digestive system: cirrhosis of the liver, chronic hepatitis, hepatocerebral dystrophy, acute and chronic pancreatitis, diseases of the biliary tract, gastric ulcer and duodenal ulcer, ulcerative colitis.Diseases of the endocrine system: diabetes mellitus, severe forms of thyrotoxicosis and adrenal insufficiency or dysfunction, thymomegaly, congenital enzymopathy.Systemic connective tissue diseases: systemic lupus erythematosus, discoid lupus, rheumatism, rheumatoid arthritis, systemic vasculitis, systemic scleroderma.Blood diseases: leukemia, Hodgkin's disease, aplastic anemia, hemophilia, Werlhof's disease; hemolytic conditions; deficiency anemia.Allergic diseases: bronchial asthma; asthmatic bronchitis, asthmatic syndrome (associated with a respiratory infection); severe anaphylactic reactions (shock, angioedema of the larynx, etc.) to a variety of food, drug and other allergens; allergic reactions to individual allergens (various rashes, clinical disorders, etc.).Diseases of the ear, throat, nose: chronic tonsillitis and adenoiditis requiring surgical treatment; chronic otitis.Surgery within the previous 2 months.Simultaneous participation in other clinical trials.Persons with alcohol, drug or drug addiction.The presence of mental illness and neurasthenia.Previous treatment with human immunoglobulin preparations, if less than 6 months have passed since the treatment.Failure to meet inclusion criteria.Vaccination with any vaccine less than 2 months prior to study entry.Premenopausal women (last menstrual period ≤ 1 year prior to signing the informed consent) who are not surgically sterile.Women who have reproductive potential or do not use or plan to use approved birth control products throughout the study nor they agree to a urine pregnancy test while participating in the study. Acceptable birth control methods include extrauterine devices, oral, implanted, or injectable contraceptives.Nervous and mental diseases: injuries of the central nervous system (CNS) with residual effects, encephalitis and encephalomyelitis (including post-vaccination), meningitis, polyradiculoneuritis (including those in the past), epilepsy, decompensates or subcompensated hydrocephalus, demyelinating and degenerative lesions of the nervous system (muscle degeneration, etc.), stroke; compensated hydrocephalus, Down's disease, Little's disease, CNS trauma without residual effects, history of febrile convulsions, mental illness.Positive analysis for HIV, viral hepatitis B and C, lues.Concomitant diseases that, in the opinion of the investigator, may interfere with the evaluation of the objectives of the study.Serious post-vaccination reactions/complications associated with any previous vaccination.