Italian Medicines Agency Agenzia Italiana del Farmaco

FAQ - Viral Vector COVID-19 Vaccines

FAQ - Viral Vector COVID-19 Vaccines

28 April 2021

The European Medicines Agency and AIFA have authorized two COVID-19 viral vector vaccines: Vaxzevria Vaccine (ex COVID-19 Vaccine AstraZeneca) and COVID-19 Vaccine Janssen.

Mechanism of action

1. What is the mechanism of action of DNA vaccines that use adenoviruses as transporters?

Some vaccines approved for the COVID-19 vaccination campaign use adenoviruses to send the DNA fragment containing the instructions for producing the Spike protein present on the surface of the COVID-19 virus into human cells. The adenoviruses used as transporters have been rendered unable to replicate and therefore cannot spread throughout the body.
After vaccination, these adenovirus transporters enter some cells of the vaccinated person where the DNA fragment carried by the virus initiates the temporary production of the Spike protein.
The presence of this foreign protein will stimulate the immune system to react by producing antibodies which, by binding to the Spike protein, will prevent the COVID-19 virus from entering the cells. The presence of the foreign Spike protein will also activate T lymphocytes that drive antibody production and kill virus-infected cells.
After vaccination, some of the lymphocytes that reacted against the Spike protein survive for several months. The presence of these "memory lymphocytes" will allow the vaccinated person’s immune system to rapidly activate a formidable response against a possible invasion by the COVID-19 virus.
These vaccines do not use whole, active or inactivated viruses or fragments of the virus, but only a small segment of DNA that contains the instructions for making the Spike protein. The production of the foreign Spike protein will end within a short time.

COVID-19 Vaccine AstraZeneca (Vaxzevria)

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

Vaxzevria vaccine is a vaccine intended to prevent COVID-19 disease in people aged 18 and over. It is the third vaccine authorised by AIFA in Italy (30 January 2021). In Italy it is currently recommended preferably for the population aged 60 and over.

2. How is it administered?

Vaxzevria is administered as two injections, into the muscle of the upper arm. People who have been vaccinated with the first dose of Vaxzevria should receive the second dose of the same vaccine to complete the vaccination course during the 12th week and at least ten weeks after the first dose.

3. What does it contain?

The vaccine is composed of a chimpanzee adenovirus unable to replicate itself (ChAdOx1 - Chimpanzee Adenovirus Oxford 1) and modified to carry the genetic information intended to produce the Spike protein of the SARS-CoV-2 virus. It is a genetically modified organism. The viral vector technology used for this vaccine has already been successfully tested and is used to prevent other diseases.
The inactive ingredients (excipients) are: L-histidine, L-histidine hydrochloride monohydrate, Magnesium chloride hexahydrate, Polysorbate 80 (E 433), Ethanol, Sucrose, Sodium chloride, Disodium edetate (dihydrate), water for injections. The vaccine does not contain preservatives.

4. What is the expected interval between the administration of the first and second dose?

The temporary authorisation of Vaxzevria by the EMA and AIFA provides that the second dose of the vaccine should be administered between 28 and 84 days after the first administration. However, new data collected from ongoing studies seem to offer the opportunity to indicate a longer interval between the first and second dose. In particular, the new data published in February 2021 as a preprint in the 'Lancet' magazine indicate an efficacy equal to 82% when the second dose is administered during the twelfth week.
This is why AIFA considers it useful to indicate the administration of the second dose of the Vaxzevria vaccine ideally during the twelfth week and in any case at least ten weeks after the first dose.

5. How were clinical trials conducted?

The evaluation of the clinical efficacy of Vaxzevria is based on the interim analysis of data from two ongoing clinical trials that included people over 18 years of age: study COV002 phase II/III and study COV003 phase III, conducted in the UK and Brazil respectively. 87% of the participants were aged between 18 and 64, 13% were aged 65 or older. 55.1% of the subjects were women. The studies did not involve people with severe or uncontrolled diseases, with severe immunosuppression, pregnant women, and people who already had COVID-19 disease.
A total of 6,106 participants received two doses of Vaxzevria, while 6,090 participants in the control group received either a meningococcal vaccine or a saline solution.
Due to logistical constraints, the interval between dose 1 and dose 2 ranged from 3 to 23 weeks with 86.1% of participants receiving the two doses within a 4 to 12 week interval.

6. How effective is it?

In subjects vaccinated with the approved dosage regimen (2 doses 4-12 weeks apart), 64 cases of COVID-19 were observed out of 5,258 vaccinated individuals and 154 cases out of 5,210 in the control group. Overall, the vaccine efficacy of Vaxzevria was found to be 59.5% in preventing symptomatic disease. In participants with one or more comorbidities, vaccine efficacy was very similar (58.3%).
In participants who received the second dose 12 weeks after the first, the efficacy 14 days after the second dose was 82.4% (see question "What is the expected interval between the administration of the first and second dose?").
In all participants who received at least one dose of the vaccine, no cases of hospitalisation were observed from 22 days after the first dose (0%, out of 8,032), compared to 14 cases (0.2%, out of 8,026), one of which was fatal, reported for the control group.

7. Is protection effective immediately after injection?

Protection begins approximately 3 weeks after the administration of the first dose of Vaxzevria and persists for up to 12 weeks. However, protection may be incomplete for up to 15 days after the second dose. Moreover, as with all vaccines, vaccination with Vaxzevria may not protect all vaccinated individuals.

8. What adverse reactions were observed during the trials?

Most of the reported adverse reactions were mild to moderate in severity and events usually resolved within a few days after vaccination.
Compared to what was observed in younger participants, adverse reactions, which are commonly expected with the administration of a vaccine, were generally less frequent and milder in participants over the age of 65.
In clinical studies, serious adverse reactions after administration of Vaxzevria were very rare.

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

The most frequently observed adverse reactions during the current vaccination campaign are fever, headache, muscle or joint pain. These are non-serious, mild or moderate reactions which, although annoying, resolve within a few hours or a few days, often without even resorting to symptomatic treatments (painkiller or similar).
The total rate of reports received for this vaccine is reported in the monthly adverse reaction reports published in the dedicated section of the AIFA website. During the month of March 2021, the European pharmacovigilance system received reports of thrombotic and embolic events following the administration of the Vaxzevria vaccine.
The EMA has determined that the benefits of the vaccine in preventing COVID-19 disease (which itself causes clotting problems) far outweigh the risks, the vaccine does not increase the overall risk of thromboembolic events, and there are no issues with individual batches. Rare venous thrombotic events at unusual sites have been recognised as possible side effects of Vaxzevria vaccine. No predisposing risk factors have been confirmed; since most cases have occurred in people under the age of 60, the Italian Ministry of Health has recommended preferential use in people over the age of 60 and established that those who have already received a first dose of the Vaxzevria vaccine can complete the vaccination cycle with the same vaccine.

10. How is Vaxzevria prepared and stored?

The vaccine can be stored for 6 months at temperatures between 2 °C and 8 °C, if the package remains intact. After opening the vial, it can be stored in the refrigerator (2 °C – 8 °C) for no longer than 48 hours and at room temperature (below 30 °C) for up to 6 hours. After this period of time, the product must be discarded.
The multidose vial can contain 8 or 10 doses, although one or more additional full doses of 0.5 mL can be obtained using appropriate syringes. In no case is dilution required: the suspension is ready for use. Any residue from different vials, even belonging to the same batch number, should never be mixed.
Vaxzevria contains genetically modified organisms, as allowed by the derogation from certain provisions of Directive 2001/18/EC, approved by the European Parliament in July 2020. Any unused vaccine or waste material derived from this medicine should be disposed of in compliance with the guidance for genetically modified organisms or biohazardous waste. Spills should be disinfected using agents with activity against adenovirus.

COVID-19 Vaccine Janssen

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

The COVID-19 Vaccine Janssen is a viral vector vaccine intended to prevent SARS-CoV-2 disease (COVID-19) in people aged 18 years and older. It is designed to prepare the immune system to recognize and counteract SARS-CoV-2.

2. How is it administered?

The COVID-19 Vaccine Janssen is administered as a single 0.5 ml dose by intramuscular injection only, into the upper arm.

3. What does it contain?

The active substance is the modified adenovirus (Ad26.COV2-S) encoding the SARS-CoV-2 spike protein. It is a genetically modified organism. The inactive ingredients (excipients) are: 2-hydroxypropyl-β-cyclodextrin (HBCD), citric acid monohydrate, ethanol, hydrochloric acid, polysorbate-80, sodium chloride, sodium hydroxide, trisodium citrate dihydrate, water for injections. This vaccine does not contain adjuvants, preservatives, materials of animal origin or foetal tissue.

4. How were the clinical trials conducted?

The evaluation of the clinical efficacy of COVID-19 Vaccine Janssen is based on the interim analysis of an ongoing randomised, double-blind, placebo-controlled phase 3 study (COV3001) conducted in the United States, South Africa and Latin American countries to assess the efficacy, safety, and immunogenicity of a single-dose of COVID-19 Vaccine Janssen for the prevention of COVID-19 in adults aged 18 years and older.
A total of 21.895 adults received COVID-19 Vaccine Janssen while 21.888 adults received placebo, that is a product identical in all respects to the vaccine, but not active. Participants were followed for a median of 58 days (range: 1-124 days) after vaccination
Out of the total number of participants, the efficacy was however evaluated on a population of 39.321 (of which 19.630 received the vaccine and 19.691 received the placebo). 79.7% of individuals who received the vaccine were 18 to 64 years old, 20.3% aged 65 or older. 44.3% of individuals were female; 39.9% of individuals had at least one pre-existing comorbidity associated with increased risk of progression to severe COVID-19.

5. How effective is it?

Fourteen days after vaccination, 116 cases of COVID-19 out of 19,630 vaccinated individuals were observed compared to 348 out of 19,691 in the control group. Therefore, COVID-19 Vaccine Janssen efficacy against occurrence of moderate to severe symptomatic COVID-19 disease was 66.9%. The result includes people aged 60 years and over.
The efficacy observed was 66.1 % 28 days after vaccination (66 cases observed among individuals receiving the COVID-19 Vaccine Janssen compared to 193 cases in the placebo group).  Furthermore, 14 days after vaccination, 14 severe cases in the vaccine group and 60 cases in the control group were observed (76.7 % efficacy in preventing severe/critical disease), whereas 28 days after vaccination 5 cases in the vaccine group and 34 in the placebo group were observed (85.4 % efficacy).
Of the severe cases with onset at least 14 days after vaccination- 14 in vaccine group and 60 in the placebo group- 2 and 6 respectively were hospitalised. Three individuals died (all in the placebo group). Overall, the efficacy of the vaccine was similar in the different subgroups based on age, comorbidity, gender and ethnicity.

6. Is protection effective immediately after injection?


Protection with COVID-19 Vaccine Janssen starts around 14 days after vaccination.

7. What adverse reactions were observed during the trials?

Most adverse reactions reported were mild to moderate in severity and usually the events resolved within a few days.
Compared to younger participants, adverse reactions, which are commonly expected after vaccination, were reported less frequently and were generally milder in adults aged 65 years and older. Rare side effects (that occurred in less than 1 in 1,000 people) have been hypersensitivity (allergy) and skin allergic reaction (urticaria).
Serious adverse reactions following administration of the COVID-19 Vaccine Janssen during clinical trials have been very rare.

8. What adverse reactions were observed during the Janssen vaccine vaccination campaign?

On 13 April 2021, in applying a precautionary principle, after more than 6.8 million doses, the FDA recommended pausing use of the Janssen vaccine, following reported cases of a rare and severe type of blood clot in individuals who had received the vaccine. In these cases, a type of blood clot called cerebral venous sinus thrombosis (CVST) was observed in combination with low levels of blood platelets (thrombocytopenia). All six cases occurred among women between the ages of 18 and 48, and symptoms occurred 6 to 13 days after vaccination.
Pending the decision of the EMA, Johnson & Johnson decided autonomously to suspend the delivery of doses to the European Union.
On 20 April, the Pharmacovigilance Risk Assessment Committee (PRAC) of EMA concluded the benefits of the Janssen vaccine outweigh the risks and confirmed authorisation for the entire population over 18 years.  
In Italy, the Ministry of Health, after obtaining the opinion of AIFA's Technical Scientific Committee, recommended its use for individuals over 60 years of age.

9. How is the Janssen vaccine prepared and stored?

The vaccine can be stored for 2 years at -25 °C to -15 °C if the package remains intact. Once removed from the freezer, the unopened vaccine vial may be stored refrigerated at 2°C to 8°C, protected from light, for a single period of up to 3 months, not exceeding the printed expiry date. Once thawed, the vaccine should not be re-frozen.
After opening the vaccine can be stored between 2°C-8°C for a maximum of 6 hours or remain at room temperature (maximally 25°C) up to 3 hours after first puncture of the vial.
The multidose vial contains 5 doses of 0.5 ml, no dilution is required. Any residues from different vials, even those belonging to the same batch number, shall not be mixed.
Covid-19 Vaccine Janssen contains genetically modified organisms, in accordance with the derogation from certain provisions of Directive 2001/18/EC, approved by the European Parliament in July 2020. Any unused vaccine or waste materials derived from this medicine should be disposed of in compliance with the guidelines for GMOs or biohazardous waste. Potential spills should be disinfected with agents with viricidal activity against adenovirus.

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