Convacell^® (Emulsion) Instructions for Use

Marketing Authorization Holder

St. Petersburg Research Institute of Vaccines and Sera of the FMBA, FSUE (Russia)

ATC Code

J07BN04 (COVID-19 vaccine, protein subunit)

Active Substance

Vaccine for the prevention of COVID-19 (Grouping name)

Dosage Form

Convacell®

Intramuscular emulsion 0.5 ml/dose: 10 ampoules

Dosage Form, Packaging, and Composition

Emulsion for intramuscular administration in the form of a white or yellowish liquid; separation is allowed, which disappears after shaking.

Excipients: squalane – 15 mg, (D,L)-α-tocopherol – 5 mg, polysorbate 80 – 5 mg, disodium hydrogen phosphate dodecahydrate – 1.79 mg, potassium dihydrogen phosphate – 0.12 mg, potassium chloride – 0.1 mg, sodium chloride – 4 mg, water for injections – up to 0.5 ml.

0.5 ml (1 dose) – glass ampoules (10) – contour cell packs (1) – cardboard packs.

Clinical-Pharmacological Group

Vaccine for the prevention of coronavirus infection caused by the SARS-CoV-2 virus

Pharmacotherapeutic Group

Vaccines; viral vaccines; vaccines against COVID-19

Pharmacological Action

Characteristics. The Convacell^® vaccine is a recombinant nucleocapsid protein of the SARS-CoV-2 virus, produced in Escherichia coli, and a mixture of excipients (squalane, (D,L)-α-tocopherol, polysorbate 80) in the form of an emulsion.

Mechanism of action

Vaccination with Convacell^® induces humoral and cellular immunity that prevents the development of coronavirus infection caused by the SARS-CoV-2 virus. On the surface of the emulsion droplets of excipients, the N protein is presented to monocytes recruited from the bloodstream due to a local increase in cytokine levels. Antigen-presenting cells migrate to draining lymph nodes, activating cells of innate and adaptive immunity therein. The mechanism of action of the vaccinated individual’s immunity upon encountering COVID-19 infection has three directions: antibody response, specific cellular response, and antibody-dependent cellular cytotoxicity. The antibody response helps reduce the viral load in infected tissues. An increase in the level of antibodies to the nucleocapsid protein after vaccination was demonstrated in preclinical and clinical studies using enzyme-linked immunosorbent assays. The specific cellular response involves the recognition of nucleocapsid protein epitopes by T-cell receptors of lymphocytes on infected cells, leading to apoptosis of these cells without destruction of healthy tissue. Specific activation of T-cells after Convacell^® vaccination was demonstrated using blood samples from volunteers in phase II and IIb clinical studies using ELISPOT (IFN-γ) and flow cytometry (IFN-γ, IL-2) methods. Safe polarization of the Th1 response was shown.

The mechanism of antibody-dependent cellular cytotoxicity is due to the fact that the intact viral nucleocapsid protein is located on the surface of cells infected with SARS-CoV-2. The nucleocapsid protein is recognized by specific antibodies, then cells labeled with antibodies to the foreign viral protein are cleared by natural killer (NK) cells. This mechanism for Convacell^® was demonstrated using blood samples from volunteers in a phase II clinical study with a test for specific degranulation of NK cells in the presence of antibodies produced in response to vaccination. The nucleocapsid protein (N) is conservative and less prone to mutational changes. This makes the vaccine based on it universal for various coronavirus strains.

Immunogenicity

Clinical studies in volunteers showed the safety of the vaccine and its immunogenicity. All volunteers demonstrated production and an increase in titers of IgG antibodies to the N protein, as well as activation of a specific cellular immune response. Within the framework of phase I/II clinical study, in volunteers with single immunization, the geometric mean titer of IgG increased from the baseline of 0.153 to 4.64 on day 21 after vaccination and to 7.21 on day 42 after vaccination, and the increase in geometric mean titer on days 21 and 42 was 30.3 and 47.1 times, respectively. On days 180 and 350 of observation, the IgG levels to the N protein were 5.11 and 1.81, which exceeded the baseline level by 33.3 and 11.8 times, respectively. On the 21st and 42nd day after primary vaccination, the proportion of seropositive (for IgG) volunteers was 79.55% and 100%, respectively, and the seroconversion rate reached 79.55% and 100%, respectively. On days 180 and 350 of observation, the seroconversion rates in the single immunization group were 97.6% and 66.7%. When analyzing the antigen-specific cellular immune response, a significant increase in IFN-γ and IL-2 producing helpers was found in volunteers who received the vaccine compared to volunteers from the “Placebo” group, on the 42nd day of observation (p<0.05).

Analysis of data obtained during phase IIb/III showed that with a single immunization with the drug, the specific antibody titer increases by 14.7 times in the general population and by 20.1 times in the group of persons over 60 years of age. At the same time, the specific cellular response increases by 2.7 and 2.5 times, respectively.

The duration of post-vaccination immunity and protection is 12 months.

Indications

Prevention of the novel coronavirus infection (COVID-19) in adults aged 18 years and older.

Vaccination is especially indicated for

• Persons over 18 years of age who have not previously had and/or have not been vaccinated against coronavirus infection caused by the SARS-CoV-2 virus;
• Persons aged 60 years and older;
• Persons with chronic diseases, including diseases of the bronchopulmonary system, tuberculosis, cardiovascular diseases, diabetes mellitus and obesity;
• Persons with primary or secondary immunodeficiencies, including HIV infection, autoimmune diseases, oncological/oncohematological diseases.

Re-vaccination (booster) against coronavirus infection caused by the SARS-CoV-2 virus is carried out no earlier than 1 year after the previous vaccination.

ICD codes

Dosage Regimen

The vaccine is administered once at a dose of 0.5 ml by injection, intramuscularly into the upper third of the outer surface of the shoulder (into the deltoid muscle area).

Before use, the ampoule with the vaccine should be brought to room temperature and its contents should be gently mixed with circular movements, allowing careful turning over. In case of emulsion separation, continue mixing until the contents are homogeneous (a white or yellowish liquid).

Ampoule opening and the vaccination procedure are carried out in strict compliance with the rules of asepsis and antisepsis: before opening, the ampoule neck is wiped with a sterile napkin moistened with 70% ethyl alcohol, the ampoule is opened, the vaccine is drawn into a disposable syringe and the remaining air is removed from the syringe. The skin at the injection site is wiped with 70% ethyl alcohol.

The drug in an opened ampoule must not be stored!

Adverse Reactions

The frequency of adverse reactions is presented in accordance with the WHO classification of adverse drug reactions based on the results of conducted clinical studies.

Frequency is determined based on the following criteria: very common (≥1/10), common (≥1/100 and <1/10), uncommon (≥1/1000 and <1/100), rare (≥1/10000 and <1/1000), very rare (<1/10000, including isolated cases).

During clinical studies, the safety of Convacell^® was assessed in more than 3500 volunteers aged 18 to 60 years. Table 1 presents all adverse reactions recorded during the clinical study in this population.

Table 1. Adverse reactions noted during clinical studies in the age group 18-60 years

Despite the lack of clinical data, the possibility of neurological disorders and allergic reactions characteristic of vaccines cannot be excluded.

The patient should be informed of the need to inform the doctor about any pronounced or unlisted adverse reactions in this instruction.

Contraindications

• Hypersensitivity to any component of the vaccine or to a vaccine containing similar components;
• Allergic or post-vaccination complications to previous administration of the vaccine;
• Acute infectious and non-infectious diseases, exacerbation of chronic diseases – vaccination is carried out 2-4 weeks after recovery or remission. For non-severe acute respiratory viral infections, acute infectious gastrointestinal diseases – vaccination is carried out after temperature normalization;
• Pregnancy;
• Breastfeeding period;
• Age under 18 years (due to lack of data on efficacy and safety).

With caution

Use the vaccine with caution in chronic diseases of the liver and kidneys, endocrine diseases (severe thyroid dysfunction and decompensated diabetes mellitus), severe diseases of the hematopoietic system, epilepsy and other diseases of the central nervous system, acute coronary syndrome and acute cerebrovascular accident, myocarditis, endocarditis, pericarditis, primary and secondary immunodeficiencies, autoimmune diseases, in patients with allergic reactions.

Due to lack of information, vaccination may pose a risk for the following groups of patients

• With autoimmune diseases (stimulation of the immune system may lead to exacerbation of the disease, special caution should be exercised with patients with autoimmune pathology prone to the development of severe and life-threatening conditions);
• With malignant neoplasms.

The decision to vaccinate should be based on an assessment of the benefit-risk ratio in each specific situation.

Use in Pregnancy and Lactation

The drug is contraindicated during pregnancy and breastfeeding, as its efficacy and safety under these physiological conditions have not been studied.

Pediatric Use

Use in children and adolescents under 18 years of age is contraindicated (due to lack of data on efficacy and safety).

Special Precautions

The vaccine is for intramuscular administration only! Do not administer intravenously!

The drug is not suitable for use if the ampoules have damaged integrity or labeling, if physical properties (color) have changed, if foreign particles are present in the emulsion, if the expiration date has expired, or if storage and/or transportation requirements have been violated.

Before vaccination, vaccinees must be examined by a doctor (paramedic) with mandatory thermometry. If the temperature is above 37°C (98.6°F), vaccination is not performed.

In the rooms where vaccination is carried out, it is necessary to have anti-shock therapy means in accordance with the order of the Ministry of Health of the Russian Federation dated December 20, 2012 No. 1079n “On approval of the standard of emergency medical care for anaphylactic shock”. The vaccinated person must be under the supervision of a healthcare professional for 30 minutes after vaccination.

Used ampoules are disposed of in accordance with the requirements of the current legislation.

The use of immunosuppressive therapy (drugs that suppress the immune system, including chemotherapy, some types of immunobiological therapy, long-term use of high doses of corticosteroids) may reduce the immune response to vaccination. The attending physician should determine the advisability of vaccination and/or select the optimal timing for vaccination during periods of least intensive treatment.

Similar to other vaccines, a protective immune response may not occur in all vaccinated individuals.

The decision to vaccinate should be made by a doctor based on an assessment of the benefit-risk ratio in each specific situation, including in the presence of the diseases listed below

• Chronic diseases of the liver and kidneys, endocrine diseases (severe thyroid dysfunction and decompensated diabetes mellitus), primary and secondary immunodeficiencies, patients with allergic reactions;
• Autoimmune diseases (stimulation of the immune system may lead to exacerbation of the disease, special caution should be exercised with patients with autoimmune pathology prone to the development of severe and life-threatening conditions);
• Malignant neoplasms.

If the doctor (healthcare worker) decides on the need for simultaneous administration of Convacell^® with another vaccine, mixing them in the same syringe and administration into the same body site is not allowed.

Effect on the ability to drive vehicles and mechanisms

Studies on the effect of the Convacell^® vaccine on the ability to drive vehicles and potentially dangerous mechanisms have not been conducted.

Overdose

No cases of overdose have been reported.

Considering that the vaccine is dispensed only to medical and preventive institutions, and vaccination itself is carried out only by qualified medical personnel, the risk of overdose is extremely low. However, it can be assumed that in case of accidental overdose, allergic reactions may develop. There are no specific antidotes for the drug. Therapeutic measures in this case will include symptomatic therapy as indicated.

Drug Interactions

Special studies of drug interactions have not been conducted.

Mixing the Convacell^® vaccine with other vaccines or other medicinal products in the same syringe is not allowed, as there are no data on pharmaceutical interaction.

Storage Conditions

Store in a light-protected place at a temperature of 2 to 8°C (46.4°F). Do not freeze.

Shelf Life

Shelf life – 1 year. Do not use after the expiration date.

Keep out of reach of children.

Transport conditions

Transport at a temperature of 2 to 8°C (46.4°F). Do not freeze.

Dispensing Status

For medical and preventive institutions.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.