Italian Medicines Agency

CVaxzevria Vaccine is a vaccine indicated for preventing the 2019 coronavirus disease (COVID-19) in people aged 18 and over. It is designed to prepare the immune system to identify and counter the coronavirus (SARS-CoV-2) responsible for the COVID-19 disease.

The vaccine is composed of a chimpanzee adenovirus unable to replicate (ChAdOx1 - Chimpanzee Adenovirus Oxford 1) and modified to convey the genetic information coding for the SARS-CoV-2 virus Spike protein.

The viral vector technology used for this vaccine has already been successfully tested and is used to prevent other diseases.

Vaxzevria Vaccine is given as two injections, into the deltoid muscle of the upper arm. People who have been vaccinated with the first dose of COVID-19 Vaxzevria vaccine should receive the second dose of the same vaccine to complete the vaccination course, ideally during the 12th week and in any case at least ten weeks after the first dose.

The provisional authorisation for the use of Vaxzevria Vaccine by EMA and AIFA provides that the second dose of the vaccine be administered within an interval ranging between 28 and 84 days from the first administration. However, new data collected from ongoing studies seem to indicate the opportunity to consider a longer interval between the first and the second dose. In particular, the new data, published in February 2021 in preprint in the 'Lancet' magazine, show an 82% efficacy when the second dose is administered during the twelfth week.

This is why AIFA deems 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.

After administration, the modified adenovirus, unable to modify, binds to the surface of human cells and penetrates into the cell nucleus. Therein it provides the genetic code to produce the coronavirus Spike protein. T lymphocytes that recognise fragments of the Spike protein on the membrane of dendritic cells and macrophages become activated, help B lymphocytes produce antibodies that neutralise the virus, and give rise to a cytotoxic cellular immune response that kills cells infected with the virus.

The immune system also produces cells with defensive memory against the coronavirus Spike protein, so facilitating recognition and rapid immune response in case of future exposure to the coronavirus responsible for COVID-19.

Vaccination therefore only introduces into the vaccinee’s cells the genetic information required to build copies of the Spike protein. The adenovirus is unable to replicate and therefore cannot spread in the vaccinee’s body. After administration, the genetic information is degraded and removed.

As with all vaccines, Vaxzevria Vaccine vaccine consists of an active ingredient and inactive ingredients which facilitate its maintenance and delivery into the vaccinee’s body.

The active ingedient is modified adenovirus (ChAdOx1-Chimpanzee Adenovirus Oxford 1) which contains the genetic code of the SARS-CoV-2 Spike protein. It is a genetically modified organism. The inactive ingredients (excipients) are:

• L-histidine
• L-histidine hydrochloride monohydrate
• Magnesium chloride hexahydrate
• Polysorbate 80 (E 433)
• Ethanol
• Saccharose
• Sodium chloride
• Disodium edetate (dihydrate)
• Water for injections

The vaccine does not contain preservatives.

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, the product must be disposed of.

The multidose vial can contain 8 or 10 doses. In no case is dilution required: the suspension is ready for use and allows the administration of at least 8 or 10 doses. Each dose is 0.5ml. In many cases it may be possible to obtain one or more additional full 0.5ml doses. Any residues from different vials must never be mixed, even if belonging to the same batch number.

Vaxzevria Vaccine contains genetically modified organisms, as allowed in derogation from some provisions of Directive 2001/18/EC, approved by the European Parliament in July 2020. The unused vaccine and waste derived from this medicine shall in any case be disposed of in compliance with the guidelines for GMOs or biohazardous waste. Any spills shall be disinfected using products active against the adenovirus.

The evaluation of the clinical efficacy of Vaxzevria Vaccine is based on the interim analysis of data from two ongoing clinical trials that included people over 18 years of age: the COV002 phase II/III study and the COV003 phase III study, conducted in the UK and Brazil respectively. 87% of the participants were aged between 18 and 64 years, 13% were aged 65 years 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.

6,106 participants received two doses of Vaxzevria Vaccine, 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 range.

In subjects vaccinated with the approved dose 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 vaccination efficacy of Vaxzevria Vaccine 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 one, 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 the second dose?").

In all participants who received at least one dose of the vaccine, no cases of hospitalisation were observed starting 22 days after dose 1 (0%, out of 8,032), compared to 14 cases (0.2%, out of 8,026), including one fatal, reported for the control group.

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

The duration of protection obtained with the vaccine is not known at the moment. Studies that are currently still ongoing may help reduce this uncertainty.

The vaccine was approved because it shows a favourable benefit/risk ratio in people over 18 years of age. In addition, the arrival of a third vaccine characterised by easier handling of use represents an important contribution to the ongoing vaccination campaign. The goal is to optimise the use of existing and new vaccines, making the most of their different characteristics.

Both messenger RNA vaccines and viral vaccines induce good protection against COVID-19. The data available to date seem to indicate that viral vaccines have a slightly lower efficacy than that of mRNA vaccines. However, it is difficult to arrive at a correct comparison based on indirect comparisons between different studies, which are in part still ongoing, and taking into account the differences between the populations studied.

All approved vaccines can be used in the entire authorized population (adults of all ages and for the Pfizer/BioNtech Comirnaty vaccine also young people aged 16-17). Vaxzevria Vaccine can also be administered to people aged over 65, with the exception of extremely vulnerable subjects, who should be preferentially administered a messenger RNA vaccine (Notice of the Ministry of Health 8 March 2021).

Vaccination cannot cause SARS-CoV-2 infection or COVID-19 disease because the Vaxzevria Vaccine does not contain active viruses, but only a genetic component that carries the information to produce specific antibodies in the vaccinee’s body.

Clinical studies conducted so far have made it possible to evaluate the efficacy of Vaxzevria Vaccine on clinically manifest forms of COVID-19. More time is required to obtain meaningful data to verify whether vaccinated people can become asymptomatically infected and infect other people. Although it is plausible that vaccination protects against infection, vaccinated people and people who are in contact with them should continue to take protective measures against COVID-19.

There are yet no data on the interchangeability between different vaccines, so those who undergo vaccination of the first dose with Vaxzevria Vaccine shall continue to use the same vaccine for the second dose as well.

Most of the adverse reactions reported were mild or 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 older than 65 years.

In clinical studies, serious adverse reactions following administration of Vaxzevria Vaccine were very rare.

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.

Experience on the use of Vaxzevria Vaccine in pregnant women is limited. Laboratory reproductive toxicity studies in animal models are not yet completed, however, based on the results of the preliminary study, no effects on fetal development are considered likely. The vaccine is not contraindicated and does not exclude pregnant women from vaccination, because pregnancy, especially when combined with other risk factors such as diabetes, cardiovascular disease and obesity, could make them more at risk of severe COVID-19.

It is not known whether Vaxzevria Vaccine is excreted in breast milk, as specific breast-feeding studies have not yet been performed.

The Istituto Superiore di Sanità (National Health Institute), through the ItOSS project, is participating in the national and international debate on these aspects and has recently published a document with the aim of supporting health professionals and pregnant and breast-feeding women in the decision-making process regarding vaccination. In general, the use of the vaccine during pregnancy and breast-feeding should be decided in close consultation with a healthcare professional after considering both benefits and risks.

Studies in animal models do not indicate that there are any harmful effects on reproductive capacity associated with vaccination. Therefore, vaccination is also indicated in women of childbearing age.

There are no data available on safety and efficacy of Vaxzevria Vaccine (ex Covid-19 Vaccine AstraZeneca) for children and adolescents under the age of 18 years.