Oxford–AstraZeneca COVID-19 vaccine
The Oxford–AstraZeneca COVID‑19 vaccine, sold under the brand names Covishield[31] and Vaxzevria[1][32] 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,[33][34][35] using as a vector the modified chimpanzee adenovirus ChAdOx1.[36] 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.[37] A study in Scotland found that, for symptomatic COVID-19 infection after the second dose, the vaccine is 81% effective against the Alpha variant (lineage B.1.1.7) and 61% against the Delta variant (lineage B.1.617.2).[38]
"Oxford/AstraZeneca", "Oxford vaccine", "AstraZeneca vaccine", and "Covishield" redirect here. For other vaccination topics, see AstraZeneca, Weatherall Institute of Molecular Medicine, and Oxford Vaccine Group.
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.[39][40] More rarely, anaphylaxis may occur; the UK Medicines and Healthcare products Regulatory Agency (MHRA) has 268 reports out of some 21.2 million vaccinations as of 14 April 2021.[40] In very rare cases (around 1 in 100,000 people), the vaccine has been associated with an increased risk of blood clots when in combination with low levels of blood platelets (embolic and thrombotic events after COVID-19 vaccination).[41][42][1] According to the European Medicines Agency, as of 4 April 2021, a total of 222 cases of extremely rare blood clots had been recorded among 34 million people who had been vaccinated in the European Economic Area (a percentage of 0.0007%).[43]
On 30 December 2020, the vaccine was first approved for use in the UK vaccination programme,[26][44][45] and the first vaccination outside of a trial was administered on 4 January 2021.[46] The vaccine has since been approved by several medicine agencies worldwide, such as the European Medicines Agency (EMA),[1][29] and the Australian Therapeutic Goods Administration (provisional approval in February 2021),[7][47] and was approved for an Emergency Use Listing by the World Health Organization (WHO).[48] As of January 2022, more than 2.5 billion doses of the vaccine had been released to more than 170 countries worldwide.[49] 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.[50]
Contraindications
The Oxford–AstraZeneca COVID-19 vaccine should not be administered to people who have had capillary leak syndrome.[64]
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.[1]
Vomiting, diarrhoea, fever, swelling, redness at the injection site and low levels of blood platelets occurred in less than 1 in 10 people.[1] Enlarged lymph nodes, decreased appetite, dizziness, sleepiness, sweating, abdominal pain, itching and rash occurred in less than 1 in 100 people.[1]
An increased risk of the rare and potentially fatal thrombosis with thrombocytopenia syndrome (TTS) has been associated with mainly younger female recipients of the vaccine.[65][66][67][68] 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.[69]
Anaphylaxis and other allergic reactions are known side effects of the Oxford–AstraZeneca COVID-19 vaccine.[1][70] The European Medicines Agency (EMA) has assessed 41 cases of anaphylaxis from around 5 million vaccinations in the United Kingdom.[70][71]
Capillary leak syndrome is a possible side effect of the vaccine.[64]
The European Medicines Agency (EMA) 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.[72]
Additional side effects include tinnitus (persistent ringing in the ears), paraesthesia (unusual feeling in the skin, such as tingling or a crawling sensation), and hypoaesthesia (decreased feeling or sensitivity, especially in the skin).[73]
Pharmacology
The Oxford–AstraZeneca COVID-19 vaccine is a viral vector vaccine containing a modified, replication-deficient chimpanzee adenovirus ChAdOx1,[36] containing the full‐length codon‐optimised coding sequence of SARS-CoV-2 spike protein along with a tissue plasminogen activator (tPA) leader sequence.[74][75] 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.[76][77][78] 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.[79] 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.[80][81]
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.[82] 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.[4]
Research
As of February 2021, the AZD1222 development team is working on adapting the vaccine to be more effective in relation to newer SARS-CoV-2 variants; redesigning the vaccine being the relatively quick process of switching the genetic sequence of the spike protein.[298] Manufacturing set-up and a small scale trial are also required before the adapted vaccine might be available in autumn.[298]
