COVID-19 Vaccines/Vaxzevria

COVID-19 Vaccine Vaxzevria (formerly AstraZeneca)

This article presents information about the COVID-19 vaccine Vaxzevrevia via extracts from documents written for vaccine recipients (patients), healthcare professionals, and the emergency use approval for the product.

This information is NOT to be interpreted as medical advice - rather it is intended to illustrate what type of information is publicly available, who publishes it, and how to access it via the links provided.

The information in each extract was current on the date shown in the reference for each document. These documents are regularly updated, so for the most current information please follow the links provided and get the latest version.

Background

The vaccine for COVID-19 developed by Oxford University and AstraZeneca was the first in the world to be approved for emergency use.

The Astrazeneca vaccine was first administered in the UK on 4 January 2021.

An announcement was made on 30 December 2020:-

30 December 2020

AstraZeneca’s COVID-19 vaccine has been approved for emergency supply in the UK, with the first doses being released today so that vaccinations may begin early in the New Year.

The UK Medicines and Healthcare products Regulatory Agency (MHRA) has provided authorisation for emergency supply of COVID-19 Vaccine AstraZeneca, formerly AZD1222, for the active immunisation of individuals 18 years or older. The authorisation recommends two doses administered with an interval of between four and 12 weeks. This regimen was shown in clinical trials to be safe and effective at preventing symptomatic COVID-19, with no severe cases and no hospitalisations more than 14 days after the second dose.

Source: AstraZeneca Press Release 30 December 2020

Source of Information for COVID-19 Vaccine Vaxzevria (formerly AstraZeneca)

The public documents are available on a UK Government webpage:-

Regulatory approval of Vaxzevria (previously COVID-19 Vaccine AstraZeneca)

Other sources are listed at the end of this article.

About the COVID-19 Vaccine Vaxzevria (formerly AstraZeneca)

Note: The information here is mainly from UK Government sources. Documents in other jurisdictions may be different.

Name of the product

Patient Information Leaflet (UK)	Vaxzevria suspension for injection COVID-19 Vaccine (ChAdOx1-S [recombinant])
Information for Healthcare Professionals (UK)	COVID-19 Vaccine AstraZeneca, solution for injection COVID-19 Vaccine (ChAdOx1-S [recombinant])
Public Assessment Report (UK)	The name of the active substance is COVID-19 Vaccine (ChAdOx1-S [recombinant]).

What it is and what it is used for

Patient Information Leaflet (UK)	Vaxzevria is a vaccine used for preventing COVID-19, caused by a virus called coronavirus (SARSCoV-2). Vaxzevria is given to adults aged 18 years and older.
Information for Healthcare Professionals (UK)	COVID-19 Vaccine AstraZeneca is indicated for active immunisation to prevent COVID-19 caused by SARS-CoV-2, in individuals ≥18 years old. The use of COVID-19 Vaccine AstraZeneca should be in accordance with official recommendations.
Public Assessment Report (UK)	Structure The active substance, ChAdOx1-S (recombinant), is a recombinant, replication-deficient (E1 and E3 deleted) chimpanzee adenovirus that encodes the SARS-CoV-2 spike protein with a tissue plasminogen activator (tPA) leader sequence. Adenoviruses are non-encapsulated, icosahedral particles (virions) between 80 and 100 nm in diameter, with prominent fibres protruding from the 12 vertices. The viral capsid is composed of three major proteins (fibre, hexon and penton) with four minor proteins (IIIa, VI, VIII and IX). The particles contain a single copy of the double-stranded DNA genome. The manufacturer has provided the DNA sequence of the 35,539 bp ChAdOx1-S (recombinant) genome. The expression cassette for the SARS-CoV-2 spike protein fused to the tPA leader uses a modified human cytomegalovirus (CMV) promoter and a bovine growth hormone polyadenylation sequence. The nucleotide sequence of the SARS-CoV-2 spike protein fused to the tPA leader encoded by ChAdOx1-S (recombinant) have been provided by the manufacturer. General properties Adenoviruses such as ChAdOx1-S (recombinant) are non-encapsulated, icosahedral particles (virions) between 80 and 100 nm in diameter, with prominent fibres protruding from the 12 vertices. The particles contain a single copy of the double-stranded DNA genome (contains a transgene to express the SARS-CoV02 virus spike [S] protein). Viral genome size The active substance, ChAdOx1-S (recombinant), has a genome size of 35,539 base pairs (bp). ChAdOx1-S (recombinant) is not the subject of a European Pharmacopoeia (Ph. Eur.) monograph.

Authorized Use

Patient Information Leaflet (UK)
Information for Healthcare Professionals (UK)	This medicinal product has been given authorisation for temporary supply by the UK Department of Health and Social Care and the Medicines & Healthcare products Regulatory Agency. It does not have a marketing authorisation, but this temporary authorisation grants permission for the medicine to be used for active immunisation of individuals aged 18 years and older for the prevention of coronavirus disease 2019 (COVID-19).
Public Assessment Report (UK)	This product has been authorised with a Conditional Marketing Authorisation (CMA). CMAs are intended for medicinal products that fulfil an unmet medical need, such as for serious and life-threatening diseases where no satisfactory treatment methods are available or where the product offers a major therapeutic advantage. CMAs may be granted where comprehensive clinical data are not yet complete, but it is judged that such data will become available soon. Adequate evidence of safety and efficacy to enable the MHRA to conclude that the benefits are greater than the risks is required. Any new information on COVID-19 Vaccine AstraZeneca will be reviewed every year and this report will be updated as necessary.
As above, Section IV.7 Discussion on the clinical aspects	Since the initial authorisation for the temporary supply of COVID 19 Vaccine AstraZeneca in the UK on 29 December 2020, the safety of this vaccine has been closely monitored.Significant safety updates to the product information, which have occurred based on post-authorisation data, include the addition of ‘anaphylaxis’, ‘angioedema’ and ‘thrombocytopenia’ as ADRs. Information has also been included about extremely rare events of ‘thrombosis with thrombocytopenia syndrome’ (TTS) that have been reported following widespread use of the vaccine, some of which have been fatal. The MHRA considered that the clinical data submitted for this application are satisfactory. The grant of a marketing authorisation is recommended.
As above, Lay Summary, page 4.	Other information about Vaxzevria A Conditional Marketing Authorisation was granted in Great Britain on 24 June 2021.

How does it work

Patient Information Leaflet (UK)	Vaxzevria stimulates the body’s natural defences (immune system). It causes the body to produce its own protection (antibodies) against the virus. This will help to protect you against COVID-19 in the future. None of the ingredients in this vaccine can cause COVID-19.
Information for Healthcare Professionals (UK)	Mechanism of action COVID-19 Vaccine AstraZeneca is a monovalent vaccine composed of a single recombinant, replication-deficient chimpanzee adenovirus (ChAdOx1) vector encoding the S glycoprotein of SARS-CoV-2. Following administration, the S glycoprotein of SARS-CoV-2 is expressed locally stimulating neutralising antibody and cellular immune responses.
Public Assessment Report (UK)	COVID-19 Vaccine AstraZeneca is a monovalent vaccine composed of a single recombinant, replication-deficient chimpanzee adenovirus (ChAdOx1) vector encoding the S glycoprotein of SARS-CoV-2. Following administration, the S glycoprotein of SARS-CoV-2 is expressed locally stimulating neutralising antibody and cellular immune responses

Fertility, pregnancy and lactation

Patient Information Leaflet (UK)	Pregnancy and breastfeeding If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor, pharmacist or nurse for advice before you receive this vaccine. There are limited data on the use of Vaxzevria in pregnant or breastfeeding women. Your doctor, pharmacist or nurse will discuss with you whether you can be given the vaccine.
Information for Healthcare Professionals (UK)	Fertility, pregnancy and lactation Pregnancy There is a limited experience with the use of COVID-19 Vaccine AstraZeneca in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryo/fetal development, parturition or post-natal development (see section 5.3). Administration of COVID-19 Vaccine AstraZeneca during pregnancy should only be considered when the potential benefits outweigh any potential risks (including those described in sections 4.4 and 4.8) for the mother and fetus. Breastfeeding It is unknown whether COVID-19 Vaccine AstraZeneca is excreted in human milk. Fertility Animal studies do not indicate direct or indirect harmful effects with respect to fertility.
Public Assessment Report (UK)	Pregnancy and breastfeeding Women who were pregnant or breastfeeding were excluded from the clinical trials. Pregnancy was reported for 21 subjects; 12 in the AZD1222 group and 9 in the control group. Of these pregnancies, 5 ended in spontaneous abortion – 2 in the AZD1222 group and 3 in the control group. Due to the limited duration of follow-up, the outcome of the remaining pregnancies is awaited. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryofetal development, parturition or post-natal development. Administration of COVID-19 Vaccine AstraZeneca in pregnancy should only be considered when the potential benefits outweigh any potential risks for the mother and fetus. It is unknown whether AZD1222 is excreted in breast milk. The product information reflects these recommendations. Use in pregnancy and lactation is included in the RMP as missing information.

Safety in special populations

Patient Information Leaflet (UK)	Vaxzevria is given to adults aged 18 years and older
Information for Healthcare Professionals (UK)	Elderly population No dosage adjustment is required. See also sections 4.4 and 5.1. Paediatric population The safety and efficacy of COVID-19 Vaccine AstraZeneca in children and adolescents (aged <18 years old) have not yet been established. No data are available.
Public Assessment Report (UK)	Paediatric population In line with the proposed indication, no data have been provided in subjects less than 18 years of age. Immunosuppression No data are currently available in immunocompromised subjects or in subjects taking immunosuppressants. Safety data is awaited in a subgroup of HIV positive subjects that were included in studies COV002 and COV005. This will be followed up in the RMP.

What Vaxzevria contains

Patient Information Leaflet (UK)	One dose (0.5 ml) contains: COVID-19 Vaccine (ChAdOx1-S* recombinant), not less than 2.5 × 108 infectious units * Recombinant, replication-deficient chimpanzee adenovirus vector encoding the SARS-CoV-2 Spike glycoprotein. Produced in genetically modified human embryonic kidney (HEK) 293 cells. This product contains genetically modified organisms (GMOs). The other excipients are L-histidine, L-histidine hydrochloride monohydrate, magnesium chloride hexahydrate, polysorbate 80 (E 433), sucrose, disodium edetate dihydrate, water for injections (see section 2 “Vaxzevria contains sodium and alcohol”).
Information for Healthcare Professionals (UK)	Excipients Sodium This medicinal product contains less than 1 mmol sodium (23 mg) per dose, and is considered to be essentially sodium-free. Ethanol This medicinal product contains 2 mg of alcohol (ethanol) per 0.5 ml dose. The small amount of alcohol in this medicinal product will not have any noticeable effects.
Public Assessment Report (UK)	One dose (0.5 mL) contains COVID-19 Vaccine (ChAdOx1-S recombinant) not less than 2.5 × 108 infectious units (Inf.U) recombinant, replication-deficient chimpanzee adenovirus vector encoding the SARS-CoV-2 Spike (S) glycoprotein. The adenovirus is a non-enveloped virus. The vaccine is produced in genetically modified human embryonic kidney (HEK) 293 cells. COVID-19 Vaccine AstraZeneca contains genetically modified organisms (GMOs). In addition to ChAdOx1-S (recombinant) this product also contains the excipients Lhistidine, L-histidine hydrochloride monohydrate, magnesium chloride hexahydrate, polysorbate 80, ethanol, sucrose, sodium chloride, disodium edetate dihydrate and water for injections. The finished product is packaged in multidose vials of either: 5 ml of suspension in a 10-dose vial (clear type I glass) with a halobutyl rubber stopper and an aluminium overseal with a plastic flip-off cap (in packs of 10 vials); or 4 ml of suspension in an 8-dose vial (clear type I glass) with a halobutyl rubber stopper and an aluminium overseal with a plastic flip-off cap. Satisfactory specifications and Certificates of Analysis have been provided for all packaging components. All primary packaging complies with European Pharmacopoeia requirements.

Warnings and Adverse Reactions

The Information for UK Healthcare Professionals lists several medical conditions which are known to have occurred after vaccination with AstraZeneca/Vaxzevrevia.

The Public Assessment Report also provides information about other medical conditions which may be potential risks.

Data about adverse events following immunization (AEFI) for the AstraZeneca/Vaxzevrevia COVID-19 vaccine are collected in the UK through the Yellow Card Scheme. An overview and instructions for obtaining the data is on the page [[Pandemic/Statistics/Yellow Card Scheme] For AEFIs related to Vaxzevria look for the item titled COVID-19 vaccine AstraZeneca analysis print.

Trial Summary

On 8 December 2020, AstraZeneca issued a Press Release to announce the publication of Phase III trial results:-

Results of an interim analysis of the Phase III programme conducted by Oxford University with AZD1222, peer-reviewed and published in The Lancet today, demonstrated that the vaccine is safe and effective at preventing symptomatic COVID-19 and that it protects against severe disease and hospitalisation. The interim analysis for efficacy was based on 11,636 participants accruing 131 symptomatic infections from the Phase III UK and Brazil trials conducted by Oxford University.

Source: AstraZeneca Press Release 8 December 2020

The Phase III results were published with the title Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK .

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Information Sources

Medicines and Healthcare products Regulatory Agency, UK Government

Information for healthcare professionals and the public about Vaxzevria (previously COVID-19 Vaccine AstraZeneca) is provided on this UK Government webpage:-
Regulatory approval of Vaxzevria (previously COVID-19 Vaccine AstraZeneca)

The documents linked from this page (as at July 2021) are:-

• Summary of Product Characteristics for Vaxzevria
• Patient Information Leaflet for Vaxzevria
• Conditions of Authorisation for Vaxzevria
• Summary of the Public Assessment Report (PAR) for Vaxzevria
• Public Assessment Report for Vaxzevria
• Information for Healthcare Professionals on COVID-19 Vaccine AstraZeneca (Regulation 174)
• Information for UK recipients on COVID-19 Vaccine AstraZeneca (Regulation 174)
• Conditions of Authorisation for COVID-19 Vaccine AstraZeneca (Regulation 174)

Some of these documents are webpages (html) but all can be viewed or downloaded in portable document format (.pdf).

Links to individual documents are not provided here as the links may change. Instead, navigate to the UK Government page for the Regulatory approval of Vaxzevria (previously COVID-19 Vaccine AstraZeneca) at https://www.gov.uk/government/publications/regulatory-approval-of-covid-19-vaccine-astrazeneca

CoronaVirus Disease 2019 (caused by SARS-CoV-2)

Severe Acute Respiratory Syndrome CoronaVirus 2

DeoxyriboNucleic Acid

The measurement of a medicine's desired effect under ideal conditions, such as in a clinical trial. Source: EMA Glossary of regulatory terms.

Human Immunodeficiency Virus

Genetically Modified Organisms

adverse event following immunisation