Italian Medicines Agency Agenzia Italiana del Farmaco

FAQ - COVID-19 mRNA vaccines

FAQ - mRNA vaccines

9 June 2021

The European Medicines Agency and AIFA have authorised two COVID-19 vaccines: Pfizer mRNABNT162b2 (Comirnaty) and COVID-19 Vaccine Moderna mRNA -1273.

vaccini mRNA generale

1. How do mRNA vaccines work?

The two vaccines based on ribonucleic acid molecules (mRNA vaccines), approved for the COVID-19 vaccination campaign, work by delivering a small segment of mRNA into some cells of the vaccinated person. This mRNA segment contains the instructions for temporarily producing the spike protein, a protein found on the surface of coronavirus SARS-Cov-2. 

In these vaccines, the small viral mRNA segment is embedded in microscopic lipid particles that, by merging with human cells, deliver such segment into the cells. Here, the viral mRNA segment starts the temporary production of the spike proteins. The person’s immune system will recognise these proteins as foreign and will activate lymphocytes and produce antibodies.

After the vaccination, some of the lymphocytes that acted against the spike protein will survive for several months. The presence of these ‘memory lymphocytes’ will enable the person’s immune system to rapidly activate a formidable response against a possible invasion of the virus responsible for COVID-19.

2. Can mRNA vaccines cause COVID-19 or other genetic modifications?

These vaccines do not use active viruses, but only a genetic component. No whole or live viruses are involved, therefore vaccines cannot cause the disease. As for all mRNAs produced by cells, the mRNA from the vaccine does not stay in the body but is broken down naturally few days after vaccination.

Vaccino Pfizer mRNABNT162b2 (Comirnaty)

1. What is it and what is it used for?

COVID-19 mRNA BNT162b2 (Comirnaty) is a vaccine for preventing the COVID-19 disease in people aged 16 years and older (it was the first vaccine authorised in Italy - on 22 December 2020). It was later authorised also for the 12-15 years age group.
The vaccine does not contain the virus itself and cannot cause the disease.

2. How is it administered?

Comirnaty is given as two injections, usually into the muscle of the upper arm, 21 days  apart.
Should it be necessary to delay the second dose by a few days, AIFA’s Technical Scientific Committee states that a 42-day interval should not be exceeded in any case. In order to achieve optimum protection, it is always necessary to complete the vaccination cycle with the second dose.

3. What does it contain?

Comirnaty contains a molecule called messenger RNA, enclosed in liposomes formed by ALC-0315 and ALC-0159, to facilitate entry into cells.

The inactive ingredients (excipients) are:

  • ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate) (ALC-0315)
  • 2-[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide (ALC-0159)
  • 1,2-Distearoyl-sn-glycero-3-phosphocholine (DSPC)
  • cholesterol
  • potassium chloride
  • potassium dihydrogen phosphate
  • sodium chloride
  • disodium phosphate dihydrate
  • sucrose
  • water for injections

4. How were clinical trials conducted?

A very large clinical trial showed that Comirnaty was effective at preventing COVID-19 in people from 16 years of age. The efficacy and safety profile of the vaccine was assessed during clinical trials that were conducted in six countries: United States, Germany, Brazil, Argentina, South Africa and Turkey. More than 44,000 people participated in these trials. Half received the vaccine and half were given a placebo, a product that is identical to the vaccine in all its aspects, but that is not active.   Efficacy was calculated in over 36,000 people from 16 years of age (including people over 75 years of age) who had no sign of previous infection.
The study showed a 95% reduction in the number of symptomatic COVID-19 cases in the people who received the vaccine (8 cases out of 18,198 had COVID-19 symptoms) compared with people who received a placebo (162 cases out of 18,325 had COVID-19 symptoms).

5. How effective is it?

The results of these trials have shown that two doses of Comirnaty given 21 days apart may prevent 95% of adults aged 16 years and over from developing COVID-19, with results broadly similar across genders, racial and ethnic groups. 
The 95% reduction refers to the difference between the 162 cases reported in the group of 18,325 people who received a placebo and the only 8 cases reported in the group of 18,198 people who received the vaccine.

6. Is protection effective immediately after injection?

No, the efficacy has been shown one week after the second dose.

7. What adverse reactions were observed during the trials?

The most common adverse reactions (affecting more than 1 in 10 people) with Comirnaty were usually mild or moderate and resolved within a few days after vaccination. These included pain and swelling at the injection site, tiredness, headache, muscle and joint pain, chills and fever. Redness at the injection site and nausea occurred in less than 1 in 10 people. Itching at the injection site, pain in extremities, enlarged lymph nodes, difficulty sleeping, feeling unwell were uncommon adverse reactions (affecting less than 1 in 100 people). Weakness in muscles on one side of face (acute peripheral facial paralysis or palsy) occurred rarely, in less than 1 in 1,000 people.

8. What serious adverse reactions were observed during the trials?

The only serious adverse reaction occurring more frequently in vaccinated people than in people who received the placebo was the enlargement of lymph nodes. However, this is a benign condition which resolves naturally.
Overall, systemic reactions were more common and pronounced after the second dose.
Reports of adverse reactions, from the least serious to the most severe, including allergic reactions, are being collected in countries where mass administration of the vaccine has already started. Countries administering the vaccine to the entire population are collecting and assessing any adverse reaction reported to the relevant pharmacovigilance system in order to define the risk profile of the vaccine. For further information, please refer to FAQs on Pharmacovigilance on COVID-19 vaccines and monthly reports on adverse reactions. 

9. What adverse reactions were observed during the Comirnaty vaccination campaign?

The most frequently observed adverse reactions during the current vaccination campaign are non-serious, mild or moderate reactions which, although annoying, resolve in a few hours or days, often without the need for symptomatic treatment (painkillers and the like).
The total rate of reports received for this vaccine is indicated in the monthly adverse reaction reports published on the dedicated section of the AIFA website.

10. How is Comirnaty prepared and stored?

Comirnaty’s shelf life is 6 months at -90 °C to -60 °C. Within the 6 months shelf-life, unopened vials may be stored and transported at -25 °C to -15 °C for a single period of up to 2 weeks and can be returned to -90 °C to -60 °C. 
Once thawed, the vaccine should not be re-frozen. Once removed from the freezer, stability data indicate that the unopened vial is stable for up to: 

  • 24 hours when stored at temperatures from -3 °C to 2 °C; 
  • a total of 4 hours when stored at temperatures from 8 °C to 30 °C; this includes the 2 hours at up  to 30 °C detailed above.

The vaccine should be reconstituted with sodium chloride 0.9% solution for injection. Once reconstituted, it should be used within 6 hours at 2 °C to 30 °C. 
The dose to be administered to each person is 0.3 mL. The multidose vial contains 2.25 mL after dilution and allows for the administration of 6 doses, although an additional full dose can be obtained using appropriate syringes. Any residue from different vials, even belonging to the same batch number, should never be mixed.

COVID-19 Vaccine Moderna mRNA-1273

1. What is it and what is it used for?

COVID-19 Vaccine Moderna mRNA -1273 (Moderna) is a vaccine for preventing coronavirus disease 2019 (COVID-19) in people aged 18 years and older. It is the second COVID-19 vaccine to be authorised by AIFA in Italy on 7 January 2021, after Comirnaty. 

2. How is it administered?

The vaccine is given as two injections, each of 0.5 mL, usually into the muscle of the upper arm, 28 days apart. Should it be necessary to delay the second dose by a few days, AIFA’s Technical Scientific Committee states that a 42-day interval should not be exceeded in any case. In order to achieve optimum protection, it is always necessary to complete the vaccination cycle with the second dose.

3. What does it contain?

Moderna contains a molecule called messenger RNA, enclosed in very small lipid particles (liposomes).
The inactive ingredients (excipients) are:

  • lipid SM-102
  • cholesterol
  • 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)
  • 1,2-Dimyristoyl-rac-glycero-3-methoxypolyethylene glycol-2000 (PEG2000 DMG)
  • tromethamol
  • tromethamol hydrochloride
  • acetic acid
  • sodium acetate trihydrate
  • sucrose
  • water for injections

4. How were clinical trials conducted?

A very large clinical trial showed that COVID-19 Vaccine Moderna was effective at preventing COVID-19 in people from 18 years of age. The efficacy and safety profile of the vaccine was assessed during clinical trials conducted at 99 centres across the United States. 30,420 people aged 18 years and above were enrolled.
Participants were divided into two groups: 15,210 received the vaccine and as many were given a placebo, a product that is identical to the vaccine in all its aspects, but that is not active. More than half (58.6%) of participants were 18 to 64 years of age, 24.8% of participants were 65 years of age and older, and 16.7% were below 65 years of age but had comorbidities that increased the risk of severe COVID-19. 47.3% were women.
Overall, 11 cases of COVID-19 were reported in the people who received the vaccine, compared with 185 cases reported in the group who had been given the placebo and who was used as the control group. This means that the vaccine showed a 94.1% efficacy in reducing the rate of symptomatic SARS-CoV-2 infection compared with the placebo.

5. How effective is it?

The results of these trials have shown that two doses of Moderna vaccine given 28 days apart were able to prevent 94.1% of adults aged 18 years and over from developing COVID-19.  The reported cases were 11 among vaccinated people and 185 in the placebo group. The results were substantially similar across age, gender and ethnic groups.
All serious COVID-19 cases (30 in total, with 1 death) occurring among study participants were recorded in the control group, confirming the vaccine’s ability to prevent the severe form of the SARS-CoV-2 disease.

6. Is protection effective immediately after injection?

No, the efficacy has been shown two weeks after the second dose.

7. What adverse reactions were observed during the trials?

The most frequently reported adverse reactions were pain at the injection site (92%), fatigue (70%), headache (64.7%), muscle pain (61.5%), chills (45.4%), nausea/vomiting (23%), enlargement of lymph nodes of the arm where the injection was received (19.8%), fever (15.5%), injection site swelling (14.7%) and redness (10%).  Adverse reactions were usually mild or moderate in intensity and resolved within a few days after vaccination. They occurred more frequently after the second dose and in younger participants (aged 18 to 65 years) compared with those aged 65 years and older.

8. What serious adverse reactions were observed during the trials?

The frequency of the most severe adverse events was comparable between the control group (1.3%) and that receiving the vaccine (1.5%). In less than 0.5% of cases, in both groups, adverse events were such as to prevent the administration of the second dose. No respiratory disorders were reported in relation to the vaccine. 
For further information, please refer to FAQs on Pharmacovigilance on COVID-19 vaccines and monthly reports on adverse reactions. 

9. What adverse reactions were observed during the Moderna vaccination campaign?

The most frequently observed adverse reactions during the current vaccination campaign are non-serious, mild or moderate reactions which, although annoying, resolve in a few hours or days, often without the need for symptomatic treatment (painkillers and the like).
The total rate of reports received for this vaccine is indicated in the monthly adverse reaction reports published on the dedicated section of the AIFA website.

10. How is Moderna vaccine prepared and stored?

The vaccine is stored at -25 °C to -15 °C. The unopened vial is stable at 2 °C to 8 °C, for maximum 30 days. 
The multidose vial contains 6.3 mL and does not require dilution. Therefore, it is ready for use and allows for the administration of 10 doses, although an eleventh full dose can be obtained using appropriate syringes.
Any residue from different vials, even belonging to the same batch number, should never be mixed.

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