COVAXIN Inactivated coronavirus vaccine: Pharmacology
COVAXIN is developed by Bharat Biotech in collaboration with the Indian Council of Medical Research (ICMR) – National Institute of Virology (NIV). It is India‘s indigenous COVID-19 vaccine by Bharat Biotech under BSL-3 (Bio-Safety Level 3) high containment facility.
COVAXIN is developed using Whole-Virion Inactivated Vero Cell. Inactivated vaccines do not replicate in the human body and are therefore unlikely to revert and cause pathological effects. COVAXIN contains a dead virus, incapable of infecting people but still able to stimulate the immune system to mount a defensive reaction against a covid infection.
1. Name and description of the medicinal product
COVAXIN Whole Virion inactivated coronavirus vaccine is a white translucent liquid free from particulate matter containing 6 micrograms of Whole-Virion Inactivated Coronavirus antigen (strain NIV-2020-770).
2. Qualitative and quantitative composition
Each dose of 0.5 ml contains
|Whole-Virion Inactivated Coronavirus antigen (strain NIV-2020-770)||6 mcg|
|Aluminium Hydroxide Gel||0.25 mg|
|TLR7/8 Agonist||15 mcg|
|2-Phenoxyethanol IP||2.5 mg|
|Phosphate Buffered Saline||q.s. to 0.5 mL|
3. Pharmaceutical form
Sterile liquid for injection.
4. Clinical particulars
4.1 Therapeutic indication
Whole Virion inactivated coronavirus vaccine is indicated for active immunization against SARS CoV2 virus infection for age 18 or more than 18 years. This vaccine is permitted for restricted use in an emergency situation in the clinical trial mode under the provision of new drugs and clinical trials rule 2019 Under Drug and cosmetic act 1940.
4.2 Posology and method of administration
Whole Virion inactivated coronavirus vaccine should be administered as two doses on day 0 and Day 28.
Method of administration: intramuscular injection (IM)
Once open multidose vials should be used as soon as possible and within six hours when kept at between 2 to 8 degrees centigrade (Open vial policy is not applicable).
- Hypersensitivity to any constituent of the vaccine,
- Pregnant and lactating mothers,
- During fever for severe infection,
- The individual below 18 years
4.4 Special warnings and precautions for use
- Do not administer intravenously, internally or subcutaneously.
- Like all other vaccine supervision and appropriate medical treatment should always be available to treat any anaphylactic reaction following immunization.
- The vaccinee should remain under medical supervision for at least 30 minutes after vaccination.
- Before use COVAXIN vaccine should be shaken well to obtain a uniform white is translucent suspension. Vial should be visually checked for the presence of any particulate matter or other coloration, if any, prior to its administration. If in doubt do not use the content of the vial. COVAXIN vaccine should not be mixed with other vaccines.
4.5 Interaction with other medicinal product
Chloroquine and corticosteroid as they impair the antibody response.
4.6 Pregnancy and lactation
Safety and effectiveness has not been established in pregnancy woman and in nursing mothers.
4.7 Effect on ability to drive and use machines
No study on the effect of of whole video on inactivated coronavirus vaccine on the ability to drive and use machines have been performed.
4.8 Undesirable effects clinical trial experience
Safety of the COVAXIN vaccine was established in the ongoing phase 1st and phase II study.
Phase 1 clinical trial was conducted in India in 375 adult healthy volunteers which is still on going. The most common local adverse event reported was injection site pain. The most common systemic adverse event reported for headache, followed by fatigue, fever, body ache, abdominal pain, nausea and vomiting. The other less common adverse events were dizziness/giddiness, tremor, sweating, cold, cough and injection site swelling. No vaccine related serious adverse events (SAE) were reported.
A Phase 2 Clinical trial was conducted in India in 380 Adolescents and adult healthy volunteers which is still ongoing. The similar adverse events were reported in phase II clinical trial. No vaccine-related serious adverse events were reported.
A phase III efficacy study is ongoing in 25800 participants and administered with first dose of vaccination with COVAXIN vaccine. no vaccine related adverse event were observed.
4.9 Immune response
In phase first clinical trial a total of 375 healthy participants were enrolled across the three groups and received three vaccine formulations. None of the participants had detectable neutralizing antibodies at baseline and lies by MNT50. The proportion of participants seroconverted post 2 weeks after the 2nd dose was 87.9%, 91.9% &82.8% in the three groups, respectively.
In phase II clinical trial a total of 380 healthy participants were enrolled among 2 group and receive 2 vaccine formulation. None of the participant had detectable neutralizing antibody at baseline analysed. The proportion of seroconverted participants of group first and group II, post 4 weeks of 2nd dose was 88.0% and 90.6 % respectively.
No case of overdose has been reported.
5. Pharmacological properties of COVAXIN
5.1 pharmacodynamic properties
Covid-19 disease is caused due to SARS CoV-2 virus infection. COVACIN vaccine has been studied in phase 1st and 2nd clinical study for safety and immunogenicity and found to be safe and immunogenic. COVAXIN vaccine has been shown to prevent covid-19 following 2 those given 4 weeks apart. The duration of protection against covid-19 is currently unknown.
5.2 pharmacokinetics property
Eveluation of pharmakokinetik property is not required for vaccine.
5.3 preclinical safety data
All the formulation were tested for immunogenicity in mice, rat and rabbits. Mice, rats and rabbits were vaccinated on day 0, 7 and 14 (n + 1 doses). Further these formulations are tested for immunogenicity, safety and protective efficacy in Syrian Hamster challenge model andNon-human primates (Rhesus macaque) challenge model. The Hamesters were vaccinated on day 0, 14, and 35 (n + 1 doses), the live SARS-CoV-2 virus was challenged through intranasal route on day 50. Likewise, nonhuman primates vaccinated on day 0 and 14, and live SARS-CoV-2 virus was challenge through the intranasal and intrathecal route on day 28. All the formulas and were found to be safe, immunogenic and provided effective protection to both the upper and lower respiratory tract.
6. Pharmaceuticals particulars
6.1 list of excipients
- Aluminium hydroxide gel
- 2-Phenoxy ethanol
- phosphate buffer
- TLR7/8 Agonist (agonist is an imidazole quinoline gallamide/IMDG)
The product should not be mixed with any other medicinal product or active immunizing agents.
6.3 storage of COVAXIN vaccine
- Store at + 2 degree to + 8 degree centigrade
- do not freeze.
- Discard if frozen.
- Shake well before use.
- Keep out of reach of children.
- Protect from light.
COVAXIN vaccine is presented in USB type 1 glass.
Authur: Swaroop Singh Jakhar M.pharm (Pharmacology)RGPV, Bhopal; B.pharm (MLSU, Udaipur)