SARS-CoV-2. U07.1
Conditions
Interventions
Intervention 1: Intervention group: Participants in this group will receive two doses (IM) of RAZI recombinant spike protein vaccine 21 days apart followed by a nasal spray 51 days after the first do
Sponsors
Razi Vaccine and Serum Research Institute
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: Having Iranian citizenship; Able to read and write preferably having Diploma; Adults aged 18 - 70 years; Body mass index 17 to 35kg/m2; Having sublingual temperature less than or equal to 37.2 ° C in the morning based on electronic thermometer; Negative IgG and IgM antibody titers for COVID-19 N antigen; Negative RT-PCR test forCOVID-19; Negative IgG ELISA for HIV; Having heart rate between 60 and 100; Signed the informed consent form; The participant agrees to reduce the risk of developing ofCOVID-19; For females of childbearing age 18 to 49years: not being pregnant based on the first day of the last menstrual period; For females of childbearing age 18to 49 years: negative pregnancy test based on bHCG on the day of screening and the day of vaccination if deemed necessary by principle investigator; For females of childbearing age 18 to 49 years: use at least one effective method of contraception (condoms, oral contraceptive pills, intrauterine device, Norplant capsule) and willing to continue using it up to three month after last vaccine dose; Unwillingness to have children and use effective methods of contraception up to three months after completion of vaccination (all participants). Confirmation by a psychiatrist that the participant's mental health and capacity allows him/her to make a decision regarding his/her participation in the trial.
Exclusion criteria
Exclusion criteria: Any ongoing, symptomatic acute or chronic illness requiring continuous medical or surgical care on the day of vaccination; Working in an occupation with a high risk of exposure to COVID-19 including medical staff, occupations with close contact with the client; Breastfeeding; Receipt any vaccine during the 30 days before the screening day; Received blood and/or any blood products and/or immunoglobulins within three months preceding the screening day; Any confirmed or suspected immunodeficient state; History of long-term use of immunosuppressive medication (defined as more than 14 continuous days) in the last 4 months leading up to screening day; Long-term use (defined as more than 14 continuous days) of systemic corticosteroids (equivalent to 10 mg or more daily prednisolone) within the past 4 months, except topical steroids; History of allergic diseases such as angioedema or anaphylactic reactions; History of any allergy to the drug or vaccine (defined as any clinical signs or symptom of itching at the injection site, urticaria in the body after injection, excessive redness at the injection site); History of autoimmune diseases (other than controlled autoimmune thyroid disease, stable celiac disease, mild psoriasis, vitiligo that does not require corticosteroid or immunosuppressive therapy); History of chemotherapy in the last 5 years; History of cancer in the last 5 years; History of serious psychiatric illnesses; History of blood disorders (dyscrasia, coagulopathy, platelet deficiency or disorder, deficiency of blood factors); Suffering from chronic obstructive pulmonary disease such as asthma and COPD that diagnosed by a specialist and is/was under medication; Suffering from ischemic heart disease that is/was under medication by a specialist , history of cardiac interventions; Suffering from uncontrolled hypertension (systolic blood pressure > 140 and diastolic blood pressure > 90); Suffering from uncontrolled diabetes (HbA1c >7) or requiring insulin treatment; History of chronic neurological diseases (including seizures and epilepsy); Any history of substance or alcohol abuse within the last 2 years; Any abnormality in the hematology or biochemical laboratory tests based on FDA toxicity score (grade >1) on the screening day; History of confirmed COVID-19; Acute febrile illness at the time of vaccination; History of acetaminophen allergy; Acute or chronic hepatitis B and C; Receiving prophylactic drug against tuberculosis; History of syncope with blood transfusion or blood observation; Splenectomy for any reason; Any close contact with a confirmed COVID-19 case within two weeks before the first dose of vaccine; History of SARS or MERS; Participate in any clinical trials (research) study other than this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Abnormal vital signs and anaphylactic reactions before and immediately after vaccination: number and percentages of participants who develop abnormal vital signs within two hours of receiving the vaccine at each doses will be recorded. Abnormal vital signs include temperature, respiratory rate, heart rate, systolic and diastolic blood pressure. Anaphylaxis is defined as an immediate systemic hypersensitivity simultaneously involving two systems. Anaphylactic reactions include: erythema, pruritus, urticaria and angioedema, bronchospasm, laryngeal edema, dizziness, hypotension, nausea, shortness of breath, wheezing, arrhythmia, cyanosis, vomiting, diarrhea, abdominal pain and will be checked up to two hours after each vaccination. Timepoint: Before vaccination and every 40 minutes up to two hours after vaccination at each dose. Method of measurement: Clinical examination.;The number and percentage of local adverse reactions within the first week post-vaccination (including pain, tenderness, erythema/redness, swelling and stiffness, itching) that will be assessed based on the severity score, duration and peak intensity. Timepoint: Seven days after 1st and 2nd vaccination (Days 0-7 and21-27) daily assessment. Method of measurement: They will be assessed through daily telephone calls. Furthermore symptom registration cards will be given to each patient at the time of vaccination and they will be asked to bring them back on the next visit.;The number and percentage of systemic adverse event within the first week post-vaccination (including nausea and vomiting, diarrhea, headache, fatigue, muscle pain) that will be assessed based on the severity score, duration and intensity. Timepoint: Seven days after each vaccination step (Days 0-7 and 21-27 and 51-57) daily assessment. Method of measurement: They will be assessed through daily telephone calls. Furthermore symptom registration cards will be given to each patient at the time of vaccination and they will be asked to bring | — |
Secondary
| Measure | Time frame |
|---|---|
| Neutralizing antibody activity: Neutralizing antibody titers will be measured on day zero and day 35 (2 weeks after the second dose) in all participants. Measurements in other times will only be performed on 10% of participants. The following tasks will be performed during the conduct of this test. 1- In vitro assessment of inhibitory effect of antibody on the binding of Spike antigen with human ACE2 receptor and 2- Assessing VNT titer. Timepoint: Humoral immunity will be assessed based on the neutralizing antibody titers on days 0, 35 and months 3 and 6, and comparisons will be done with day 0. Method of measurement: Virus Nutralization Test (VNT).;The cell-mediated immunity will be evaluated by counting the number of CD3, CD4 and CD8 cells and joint calculation of CD3 and CD4 and CD3 and CD8 . IFN-?,TNF-a, and interleukins 2, 4, 6, and 17 will also be measured. Evaluation of cell mediated immunity will be performed only in 10% of participants in each group. Cell mediated immunity will be measured in all participants on day 35 (2 weeks after the second dose). Summary of the measures performed in this section are as follows: 1-Assessment of CD4 to CD8 cell proportions after stimulation of PBMC (Peripheral Blood Mononuclear Cells) by inactivated virus and recombinant spike protein using flow cytometry 2- Assessment of specific proliferation of PBMC cells stimulated by inactivated virus and recombinant spike protein using flow cytometry 3 -Assessment of TH1 and TH2 specific cellular immunity after PBMC stimulation in vaccinated individuals with recombinant spike protein to determine the levels of interferon-gamma, interleukin-4, tumor necrosis factor-alpha and interleukin 6 using Eli spot and ELISA kit. Timepoint: Cell mediated immunity will be assessed on days 0, 35 and months 3 and 6 and comparison will be made between day 0 and other time points. Method of measurement: Immunologic lab tests.;The number and percentage of people who shows abnormal laboratory findings | — |
Countries
Iran (Islamic Republic of)
Contacts
Public ContactMohammad Hossein Fallah Mehrabadi
Razi Vaccine and Serum Research Institute
Outcome results
None listed