Oxford–AstraZeneca COVID-19 vaccine
The Oxford–AstraZeneca COVID19 vaccine, sold under the brand names Covishield and Vaxzevria among others, is a viral vector vaccine for the prevention of COVID-19. It was developed in the United Kingdom by Oxford University and British-Swedish company AstraZeneca, using as a vector the modified chimpanzee adenovirus ChAdOx1. The vaccine is given by intramuscular injection. Studies carried out in 2020 showed that the efficacy of the vaccine is 76.0% at preventing symptomatic COVID-19 beginning at 22 days following the first dose and 81.3% after the second dose. A study in Scotland found that, for symptomatic COVID-19 infection after the second dose, the vaccine is 81% effective against the Alpha variant and 61% against the Delta variant.
The vaccine is stable at refrigerator temperatures and has a good safety profile, with side effects including injection-site pain, headache, and nausea, all generally resolving within a few days. More rarely, anaphylaxis may occur; the UK Medicines and Healthcare products Regulatory Agency has 268 reports out of some 21.2million vaccinations as of 2021. In very rare cases, the vaccine has been associated with an increased risk of blood clots when in combination with low levels of blood platelets. According to the European Medicines Agency, as of 4 April 2021, a total of 222 cases of blood clots had been recorded among 34 million people who had been vaccinated in the European Economic Area.
On 30 December 2020, the vaccine was first approved for use in the UK vaccination programme, and the first vaccination outside of a trial was administered on 4 January 2021. The vaccine has since been approved by several medicine agencies worldwide, such as the European Medicines Agency, and the Australian Therapeutic Goods Administration, and was approved for an Emergency Use Listing by the World Health Organization. More than 3billion doses of the vaccine were supplied to countries worldwide. Some countries have limited its use to elderly people at higher risk for severe COVID-19 illness due to concerns over the very rare side effects of the vaccine in younger individuals.
The vaccine is no longer in production. AstraZeneca withdrew its marketing authorizations for the vaccine from the European market in March 2024, and worldwide by May 2024.
Medical uses
The Oxford–AstraZeneca COVID19 vaccine is used to provide protection against infection by the SARS-CoV-2 virus in order to prevent COVID-19 in adults aged 18 years and older. The medicine is administered by two doses given by intramuscular injection into the deltoid muscle. The initial course consists of two doses with an interval of 4 to 12 weeks between doses. The World Health Organization recommends an interval of 8 to 12 weeks between doses for optimal efficacy., there is no evidence that a third booster dose is needed to prevent severe disease in healthy adults.
Effectiveness
Preliminary data from a study in Brazil with 61 million individuals from January to June 2021, indicate that the effectiveness against infection, hospitalization and death is similar between most age groups, but protection against all these outcomes is significantly reduced in those aged 90 year of age or older, attributable to immunosenescence.A vaccine is generally considered effective if the estimate is ≥50% with a >30% lower limit of the 95% confidence interval. Effectiveness is generally expected to slowly decrease over time.
| Doses | Severity of illness | Delta | Alpha | Gamma | Beta |
| 1 | Asymptomatic | ||||
| 1 | Symptomatic | ||||
| 1 | Hospitalization | ||||
| 2 | Asymptomatic | ||||
| 2 | Symptomatic | ||||
| 2 | Hospitalization |
Preliminary data suggest that the initial two-dose regimen is not effective against symptomatic disease caused by the Omicron variant from the 15th week onwards. A regimen of two doses of the Oxford–AstraZeneca vaccine followed by a booster dose of the Pfizer–BioNTech or the Moderna vaccine is initially about 60% effective against symptomatic disease caused by Omicron, then after 10 weeks the effectiveness drops to about 35% with the Pfizer–BioNTech and to about 45% with the Moderna vaccine. The vaccine remains effective against severe disease, hospitalization and death.
Contraindications
The Oxford–AstraZeneca COVID-19 vaccine should not be administered to people who have had capillary leak syndrome.Adverse effects
The most common side effects in the clinical trials were usually mild or moderate and got better within a few days after vaccination.Vomiting, diarrhoea, fever, swelling, redness at the injection site and low levels of blood platelets occurred in less than 1 in 10 people. Enlarged lymph nodes, decreased appetite, dizziness, sleepiness, sweating, abdominal pain, itching and rash occurred in less than 1 in 100 people.
An increased risk of the rare and potentially fatal thrombosis with thrombocytopenia syndrome has been associated with mainly younger female recipients of the vaccine. Analysis of VigiBase reported embolic and thrombotic events after vaccination with Oxford–AstraZeneca, Moderna and Pfizer vaccines, found a temporally related incidence of 0.21 cases per 1 million vaccinated-days.
Anaphylaxis and other allergic reactions are known side effects of the Oxford–AstraZeneca COVID-19 vaccine. The European Medicines Agency has assessed 41 cases of anaphylaxis from around 5million vaccinations in the United Kingdom.
Capillary leak syndrome is a possible side effect of the vaccine.
The European Medicines Agency listed Guillain-Barré syndrome as a very rare side effect of the Oxford–AstraZeneca COVID-19 vaccine and added a warning in the product information.
Additional side effects include tinnitus, paraesthesia, and hypoaesthesia.
Pharmacology
The Oxford–AstraZeneca COVID-19 vaccine is a viral vector vaccine containing a modified, replication-deficient chimpanzee adenovirus ChAdOx1, containing the full‐length codon‐optimised coding sequence of SARS-CoV-2 spike protein along with a tissue plasminogen activator leader sequence. The adenovirus is called replication-deficient because some of its essential genes required for replication were deleted and replaced by a gene coding for the spike protein. However, the HEK 293 cells used for vaccine manufacturing, express several adenoviral genes, including the ones required for the vector to replicate. Following vaccination, the adenovirus vector enters the cells and releases its genes, in the form of DNA, which are transported to the cell nucleus; thereafter, the cell's machinery does the transcription from DNA into mRNA and the translation into spike protein. The approach to use adenovirus as a vector to deliver spike protein is similar to the approach used by the Johnson & Johnson COVID-19 vaccine and the Russian Sputnik V COVID-19 vaccine.The protein of interest is the spike protein, a protein on the exterior of the virus that enables SARS-type coronaviruses to enter cells through the ACE2 receptor. Following vaccination, the production of coronavirus spike protein within the body will cause the immune system to attack the spike protein with antibodies and T-cells if the virus later enters the body.
Manufacturing
To manufacture the vaccine the virus is propagated on HEK 293 cell lines and then purified multiple times to completely remove the cell culture.The vaccine costs around to per dose to manufacture. On 17 December 2020, a tweet by the Belgian Budget State Secretary revealed that the European Union would pay per dose, The New York Times suggesting the lower price might relate to factors including investment in vaccine production infrastructure by the EU.
the vaccine active substance was being produced at several sites worldwide, with AstraZeneca claiming to have established 25 sites in 15 countries. The UK sites at that time were Oxford and Keele, with bottling and finishing in Wrexham. Other sites at that time included the Serum Institute of India at Pune. The Halix site at Leiden was approved by the EMA on 26 March 2021, joining three other sites approved by the EU.
History
The vaccine arose from a collaboration between Oxford University's Jenner Institute and Vaccitech, a private company spun off from the university, with financing from Oxford Sciences Innovation, Google Ventures, and Sequoia Capital, among others. The first batch of the COVID-19 vaccine produced for clinical testing was developed by Oxford University's Jenner Institute and the Oxford Vaccine Group in collaboration with Italian manufacturer Advent Srl located in Pomezia. The team is led by Sarah Gilbert, Adrian Hill, Andrew Pollard, Teresa Lambe, Sandy Douglas and Catherine Green.Early development
In February 2020, the Jenner Institute agreed a collaboration with the Italian company Advent Srl for the production of a batch of 1,000 doses of a vaccine candidate for clinical trials. Originally, Oxford intended to donate the rights to manufacture and market the vaccine to any drugmaker who wanted to do so, but after the Gates Foundation urged Oxford to find a large company partner to get its COVID-19 vaccine to market, the university withdrew this offer in May 2020. The UK government then encouraged Oxford to work with AstraZeneca, a company based in Europe, instead of Merck & Co., a US-based company. Government ministers also had concerns that a vaccine manufactured in the US would not be available in the UK, according to anonymous sources in The Wall Street Journal. Financial considerations at Oxford and spin-out companies may have also played a part in the decision to partner with AstraZeneca.An initially not-for-profit licensing agreement was signed between the university and AstraZeneca PLC, in May 2020, with 1billion doses of potential supply secured, with the UK reserving access to the initial 100million doses. Furthermore, the US reserved 300million doses, as well as the authority to perform Phase III trials in the US. The collaboration was also granted of UK government funding, and of US government funding, to support the development of the vaccine. In June 2020, the US National Institute of Allergy and Infectious Diseases confirmed that the third phase of trials for the vaccine would begin in July 2020. On 4 June, AstraZeneca announced that the COVAX program for equitable vaccine access managed by the WHO and financed by CEPI and GAVI had spent $750m to secure 300million doses of the vaccine to be distributed to low-income or under-developed countries.
Preliminary data from a study that reconstructed funding for the vaccine indicates that funding was at least 97% public, almost all from UK government departments, British and American scientific institutes, the European Commission and charities.