
Questions and answers on COVID-19 mRNA vaccines
mRNA vaccines
1 March 2021
The European Medicines Agency and AIFA have authorised two COVID-19 vaccines: Pfizer mRNABNT162b2 (Comirnaty) and COVID-19 Vaccine Moderna mRNA -1273.
1.What is it and what is it used for?
COVID-19 mRNA BNT162b2 vaccine (Comirnaty) is a vaccine indicated for preventing the 2019 coronavirus disease (COVID-19) in people aged 16 years and older. It contains a molecule called messenger RNA (mRNA) provided with the instructions for producing a protein present on SARS-CoV-2, the virus responsible for COVID-19 disease. The vaccine does not contain the virus itself and cannot cause the disease.
2. How is it administered?
COVID-19 mRNA BNT162b2 vaccine (Comirnaty) is given in two injections, usually into the deltoid muscle of the upper arm, at least 21 days apart.
3. What does it contain?
COVID-19 mRNA BNT162b2 vaccine (Comirnaty) contains a messenger RNA that cannot reproduce itself in host cells, but prompts the synthesis of antigens of the SARS-CoV-2 virus (that the virus itself encodes). The S antigens of the virus stimulate the antibody response of the vaccinated person through production of neutralizing antibodies.
The messenger RNA is enclosed in liposomes formed by ALC-0315 and ALC-0159 to facilitate entry into cells.
The vaccine also contains other excipients:
1,2-Distearoyl-sn-glycero-3-phosphocholine, cholesterol, dibasic sodium phosphate dihydrate, monobasic potassium phosphate, potassium chloride, sodium chloride, saccharose, water for injections.
4. What is the dose to be injected and how many doses can be obtained per vial?
The dose of vaccine to be administered to each person is 0.3 ml. This dose should be withdrawn, under aseptic conditions and using appropriate precision syringes, from a vial of vaccine containing 2.25 ml after dilution with a 0.9% sodium chloride solution.
With an aim to use all the product available in each vial and to avoid any waste, AIFA, in accordance with the provisions of its Scientific-Technical Committee, states that, without prejudice to the need to guarantee the administration of the appropriate 0.3 ml dose to each vaccinated subject by using suitable syringes, it is possible to have at least 1 additional dose compared to the 5 doses declared in the Summary of Product Characteristics (SmPC).
Any residues from different vials, even those belonging to the same batch number, shall not be mixed.
5. How were clinical trials conducted?
A very large clinical trial showed that COVID-19 mRNA BNT162b2 vaccine (Comirnaty) is effective in preventing COVID-19 in people from 16 years of age.
The efficacy and safety profile of this vaccine was assessed in trials across six countries (USA, Germany, Brazil, Argentina, South Africa and Turkey), involving more than 44,000 participants.
Half received the vaccine and half were given a placebo, a product identical to the vaccine but inactive. Efficacy was calculated over 36,000 people aged 16 years and older (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 subjects who received the vaccine (8 cases out of 18,198 had COVID-19 symptoms) compared with the subjects who received a placebo (162 cases out of 18,325 had COVID-19 symptoms).
6. How effective is it?
Trial findings showed that two doses of COVID-19 mRNA BNT162b2 vaccine (Comirnaty) administered 21 days apart can prevent 95% of adults aged 16 years and older from developing COVID-19. Such findings were maintained across age brackets, genders and ethnic groups.
The 95% reduction refers to the difference between the 162 cases reported in the group of over 18,000 people who received a placebo and the only 8 cases reported in the group of over 18,000 people who received the vaccine.
7. Is protection effective right after the injection?
No, effectiveness has been proven one week after injecting the second dose.
8. What adverse reactions were observed during the trial?
The most frequent adverse reactions (affecting more than 1 in 10 people) observed in the COVID-19 mRNA BNT162b2 vaccine (Comirnaty) trial were usually mild or moderate and resolved within a few days after vaccination. These included pain and swelling at the injection site, fatigue, 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, limb pain, enlarged lymph nodes, difficulty in falling asleep and malaise were uncommon adverse reactions (affecting less than 1 in 100 people). Muscle weakness on one side of the face (acute peripheral facial paralysis or palsy) occurred rarely, in less than 1 in 1,000 people.
9. What serious adverse reactions were observed during the trial?
The most common serious adverse reaction was the enlargement of lymph nodes. However, this is a benign condition which resolves naturally.
Overall, systemic reactions were more frequent 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. All 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 vaccination. For further information please refer to Pharmacovigilance on COVID-19 vaccines
1. What is it and what is it used for?
COVID-19 Moderna mRNA -1273 vaccine is a vaccine indicated for preventing the 2019 coronavirus diesase (COVID-19) in people aged 18 and older. It is the second anti-COVID-19 vaccine authorised in Italy by AIFA (on 7 January 2021), after the Comirnaty vaccine. It contains a molecule called messenger RNA (mRNA) provided with the instructions for producing a protein present on SARS-CoV-2, the virus responsible for COVID-19 disease. The vaccine does not contain the virus itself and cannot cause the disease.
2. How is it administered?
The vaccine is given in two injections, of 0.5 ml each, usually into the deltoid muscle of the upper arm, at least 28 days apart.
3. What does it contain?
COVID-19 Moderna mRNA -1273 vaccine contains a messenger RNA that cannot reproduce itself in host cells, but prompts the synthesis of the Spike (S) protein of the SARS-CoV-2 virus. The viral S protein stimulates the antibody response of the vaccinated person through production of antibodies neutralizing the virus, should one come into contact with the virus. To facilitate entry into cells, the vaccine mRNA is enclosed in very small vesicles (liposomes). In addition to mRNA, the vaccine also contains: SM-102, DSPC, PEG2000 DMG, potassium chloride, potassium dihydrogen phosphate, sodium chloride, disodium phosphate dihydrate, saccharose, water for injections.
4. What are the storage and administration characteristics?
The vaccine is stored at temperatures between -15°C and -25°C, but is stable between +2°C and +8°C for 30 days if the package remains intact. The multidose vial contains 6.3 ml and does not require dilution; it is therefore ready for use and allows the administration of 10 doses, although in many cases it may be possible to obtain a complete eleventh dose of 0.5 ml. Any residues from different vials, even belonging to the same batch number, shall never be mixed.
5. How were clinical trials conducted?
A very large clinical trial proved that COVID-19 Moderna vaccine is effective in preventing COVID-19 disease in subjects aged 18 onwards. The efficacy and safety profile of this vaccine was assessed in trials conducted by 99 centres in the United States, which involved 30,420 participants from 18 years onwards.
The participants were divided into two groups: 15,210 received the vaccine and the same number were given a placebo, a product identical in all respects to the vaccine, but not active. More than half (58.6%) of the participants were aged between 18 and 64, 24.8% were 65 or older and 16.7% were younger than 65 but with concomitant diseases which increased the risk of severe COVID-19 disease. 47.3% were women. Overall, 11 cases of COVID-19 disease were recorded in the group that received the vaccine, compared to 185 in the group that received the placebo and acted as control: therefore, the vaccine showed a 94.1% efficacy in preventing infection with SARS-CoV-2 symptoms versus placebo.
6. How effective is it?
The results of these studies showed that two doses of the Moderna vaccine, administered 28 days apart, were able to prevent 94.1% of vaccinated adults aged 18 and over from developing the COVID-19 disease referred to 11 cases among the vaccinated group and 185 cases in the placebo group; the results were substantially homogeneous by age, gender and ethnicity. All severe cases of COVID-19 (30 in total, with 1 death) occurred to the study participants, were recorded in the control group. Such results confirm that the vaccine is able to prevent the severe form of the disease caused by the SARS-CoV-2 virus.
7. Is protection effective right after the injection?
No, effectiveness was completed two weeks after injecting the second dose.
8. What adverse reactions were observed during the trial?
The most common adverse reactions were pain at injection site (92%), fatigue (70%), headache (64.7%), muscle pain (61.5%), chills (45.4%), nausea/vomiting (23%), swollen lymph nodes in the arm of injection (19.8%), fever (15.5%), swelling (14.7%) and redness (10%) at the injection site. Reactions were generally mild or moderate in intensity and resolved within a few days from vaccination. Reactions were more frequent after the second dose and in younger participants aged between 18 and 65 years, compared to participants over 65 years.
9. What serious adverse reactions were observed during the trial?
The frequency of more severe adverse events was comparable between the control group (1.3%) and the group receiving the vaccine (1.5%). In less than 0.5% of cases, in both groups, adverse events were such as to prevent administration of the second dose. No cases of respiratory diseases associated with the vaccine were reported. For further information please refer to Pharmacovigilance on COVID-19 vaccines.
1. How do mRNA vaccines work?
2. How long does vaccine protection last?
3. Can mRNA vaccines cause COVID-19 disease or other genetic modifications?
4. Can vaccinated persons spread the infection to others?
5. Has the clinical trial duration been shortened to obtain such vaccines sooner?
6. Do the vaccines protect only the vaccinated persons or their family too?
7. Does vaccination allow you to go back to life as it was before?
8. Why not adopt the British strategy of immediately administering the first dose to as many people as possible and delaying the second dose?
What are the differences between the two vaccines?
The two vaccines are very similar and have been evaluated as equivalent by AIFA’s Scientific-Technical Committee, in that they adopt the same messenger RNA technology, have a very high efficacy (almost equal), they are both very safe, with modest side effects and largely resolved in a few days. Both vaccines deliver a massive immune response after two doses three to four weeks apart. They have been studied on tens of thousands of participants with the most rigorous scientific methods. Comirnaty shows efficacy data from 16 years of age onwards, Moderna from 18 years onwards.
The differences are also in the way they are presented: frozen Comirnaty to be diluted and Moderna ready and kept at refrigerator temperatures.
A synoptic comparison table between the two vaccines is available here.
1. Can pregnant or breast-feeding women be vaccinated?
2. Can children be vaccinated with the COVID-19 mRNA vaccines?
1. Who will administer the vaccine?
2. How is the absence of contraindications guaranteed?
3. Can people who receive the first dose of a COVID-19 mRNA vaccine complete the vaccination course with a second dose of the other vaccine?
4. How does the injection procedure work?
5. What is the syringe Luer lock system?
6. What is the dead space of a syringe?
1. What adverse reactions have been observed during the ongoing vaccination campaign with mRNA vaccines?
The most frequently observed adverse reactions during the current vaccination campaign are fever, headache, muscle or joint pain, injection site reactions and fatigue. These are non-serious reactions, of mild or moderate severity which, although annoying, resolve in a few hours or a few days, often without even resorting to symptomatic treatments (painkiller or similar).
As with all medicines, allergic reactions up to anaphylactic shock are also possible, although very rare. For this reason, vaccinations are carried out in a safe environment by trained personnel, and there is an observation period of at least 15 minutes after vaccination. Another aspect that is taken into account is that, following the injection, anxious reactions may also occur, with vaso-vagal phenomena ranging from the sensation of being about to faint up to actual fainting, so the staff pay attention to avoid fall injuries.
Monitoring of adverse reactions is described in the monthly surveillance reports available here.