The 

Oxford–AstraZeneca COVID-19 vaccine, codenamed AZD1222,[7] is a COVID-19

vaccine developed by Oxford University and AstraZeneca given by intramuscular injection, using as
a vector the modified chimpanzee adenovirus ChAdOx1.[18][19][20][21] One dosing regimen showed 90%
efficacy when a half-dose was followed by a full-dose after at least one month, based on mixed trials
with no participants over 55 years old.[6] Another dosing regimen showed 62% efficacy when given as
two full doses separated by at least one month.[6]
The vaccine was developed by Oxford University's Jenner Institute and Oxford Vaccine Group with
the collaboration of the Italian manufacturer Advent Srl located in Pomezia, which produced the first
batch of the COVID-19 vaccine for clinical testing.[22] The team is led by Sarah Gilbert, Adrian
Hill, Andrew Pollard, Teresa Lambe, Sandy Douglas and Catherine Green.[23][22]
The vaccine has a good safety profile with around 10% of recipients reporting mild adverse
effects including injection site pain, headache and nausea. More rarely, anaphylaxis may occur (the
UK Medicines and Healthcare products Regulatory Agency (MHRA) has 194 reports out of
approximately 9 million vaccinations as of February 2021).[24]
On 30 December 2020, the vaccine was first approved for use[11][25] in the UK's vaccination
programme,[26] and the first vaccination outside of a trial was administered on 4 January 2021.[27] The
vaccine has since been approved by several medicine agencies worldwide, such as the European
Medicines Agency,[12][14] and the Australian Therapeutic Goods Administration (TGA),[9] and has been
approved for an Emergency Use Listing (EUL) by the World Health Organization.[28]
In March 2021, a number of countries paused use of the vaccine out of fears it may be implicated in
cases of blood clotting observed in vaccine recipients.[29] The European Medicines Agency[30],
the MHRA[31] and AstraZeneca[32] have all stated that blood clotting rates were not higher than would
be expected naturally. As of 8 March 2021 across the EU and UK there have been 37 blood clotting
events out of over 17 million vaccinations.[32]

Contents

 1Vaccine platform
 2History
o 2.12020 development
o 2.2Clinical trials
o 2.3Results of Phase III trial
o 2.42021 development
o 2.5Scottish Study
 3Approvals
o 3.1Suspensions
 4Safety profile
 5Production and supply
 6References
 7External links

Vaccine platform[edit]
The AZD1222 vaccine is a replication-deficient simian adenovirus vector, containing the full‐
length codon‐optimised coding sequence of SARS-CoV-2 spike protein along with a tissue
plasminogen activator (tPA) leader sequence.[33][34]
The adenovirus is called replication-deficient because some of its essential genes were deleted and
replaced by a gene coding for the spike. Following vaccination, the adenovirus vector enters the
cells, releases its genes, those are transported to the cell nucleus, thereafter the cell's machinery
does the transcription in mRNA and the translation in proteins.
The one of interest is the spike protein, an external protein that enables the SARS-type coronavirus
to enter cells through the enzymatic domain of ACE2.[35] Producing it following vaccination will prompt
the immune system to attack the coronavirus through antibodies and T-cells if it later infects the
body.[6]

History[edit]
2020 development[edit]
In February 2020, the Jenner Institute agreed a collaboration with the Italian company Advent Srl for
the production of the first batch of a vaccine candidate for clinical trials.[36]
In March 2020,[37][38] after the Gates Foundation urged the University of Oxford to find a large
company partner to get its COVID-19 vaccine to market, the university backed off from its earlier
pledge to donate the rights to any drugmaker.[39] The U.K. government encouraged the University of
Oxford to work with AstraZeneca instead of Merck & Co., a US based company. People at Oxford
were reportedly concerned the vaccine would not be distributed worldwide. Government ministers
also had concerns that a vaccine manufactured in the U.S. would not be available in the U.K.,
according to anonymous sources in Wall Street Journal. Financial considerations at Oxford and spin-
out companies may have played a part.[40][41]
In June 2020, the US National Institute of Allergy and Infectious Diseases (NIAID) confirmed that the
third phase of testing for potential vaccines developed by Oxford University and AstraZeneca would
begin in July 2020.[42]

Clinical trials[edit]
In July 2020, AstraZeneca partnered with IQVIA to speed up US clinical trials.[43]
On 31 August 2020, AstraZeneca announced that it had begun enrolling adults for a US-funded,
30,000-subject late-stage study.[44]
On 8 September 2020, AstraZeneca announced a global halt to the vaccine trial while a
possible adverse reaction in a participant in the United Kingdom was investigated.[45][46][47] On 13
September, AstraZeneca and the University of Oxford resumed clinical trials in the United Kingdom
after regulators concluded it was safe to do so.[48] AstraZeneca was criticised for vaccine safety after
concerns from experts noting the company's refusal to provide details about serious neurological
illnesses in two participants who received the experimental vaccine in Britain.[49] While the trial
resumed in the UK, Brazil, South Africa, Japan[50] and India, it remained on pause in the US till 23
October 2020[51] while the Food and Drug Administration (FDA) investigated a patient illness that
triggered the clinical hold, according to the United States Department of Health and Human
Services (HHS) Secretary Alex Azar.[52]
On 15 October 2020, Dr João Pedro R. Feitosa, a 28-year-old doctor from Rio de Janeiro, Brazil,
who received a placebo instead of the test vaccine in a clinical trial of AZD1222, died from COVID-
19 complications.[53][54][55] The Brazilian health authority Anvisa announced that the trial would continue
in Brazil.[56]

Results of Phase III trial[edit]

On 23 November 2020, Oxford University and AstraZeneca announced interim results from the
vaccine's ongoing Phase III trials.[6][57] There was some criticism of the methods used in the report,
which combined results of 62% and 90% from different groups of test subjects given different
dosages to arrive at a 70% figure.[58][59][60] AstraZeneca said it would carry out a further multi-country
trial using the lower dose which had led to a 90% claim.[61]
The full publication of the interim results from four ongoing Phase III trials on 8 December 2020
clarified these reports.[62] In the group who received the first dose of active vaccine more than 21
days earlier, there were no hospitalisations or severe disease, unlike those receiving the placebo.
Serious adverse events were balanced across the active and control arms in the studies, i.e. the
active vaccine did not have safety concerns. A case of transverse myelitis was reported 14 days
after booster vaccination as being possibly related to vaccination, with an independent neurological
committee considering the most likely diagnosis to be of an idiopathic, short segment, spinal
cord demyelination. The other two cases of transverse myelitis, one in the vaccine group and the
other in the control group, were considered to be unrelated to vaccination.[62]
A subsequent analysis, published on 19 February, has shown an efficacy of 76% 22 days after the
first dose and increase to 81.3% when the second dose is given 12 weeks or more after the first.[63]

2021 development[edit]
In February 2021, Oxford–AstraZeneca indicated developments to adapt the vaccine to target new
variants of the coronavirus,[64] with expectation of a modified vaccine being available "in a few
months" as a "booster jab".[65] A key area of concern is whether the E484K mutation could impact the
immune response and, possibly, current vaccine effectiveness.[66] The E484K mutation is present in
the South African (B.1.351) and Brazilian (B.1.1.28) variants, with a small number of cases of the
mutation also detected in infections by the original SARS-CoV-2 virus and the UK/Kent (B.1.1.7)
variant.[66]

Scottish Study[edit]
A study was carried out by universities across Scotland of the effectiveness of first dose of Pfizer–
BioNTech and Oxford–AstraZeneca COVID-19 vaccines against hospital admissions in Scotland,
based on a national prospective cohort study of 5.4 million people. Between 8 December 2020 to 15
February 2021, 1,137,775 patients were vaccinated in the study, 490,000 of which were with the
Oxford–AstraZeneca vaccine. The first dose of the Oxford–AstraZeneca vaccine was associated
with a vaccine effect of 94% for COVID-19 related hospitalisation at 28–34 days post-vaccination.
Results for both vaccines combined showed a vaccine effect for prevention of COVID-19 related
hospitalisation which was comparable when restricting the analysis to those aged ≥80 years (81%).
The majority of the patients over the age of 65 were given the Oxford–AstraZeneca vaccine. As of
22 February 2021, the study had not been peer-reviewed.[67][68]

Approvals[edit]
Authorization and eligibility by country

show
  Full authorization

show
  Emergency authorization

  Eligible COVAX recipient
On 27 November 2020, the UK government asked the Medicines and Healthcare products
Regulatory Agency to assess the AZD1222 vaccine for temporary supply,[122] and it was approved for
use on 30 December 2020, as their second vaccine to enter the national rollout.[123]
On 4 January 2021, Brian Pinker, 82, became the first person to receive the Oxford–AstraZeneca
COVID-19 vaccine outside of clinical trials.[27]
The European Medicines Agency (EMA) received an application for a conditional marketing
authorisation (CMA) for the vaccine on 12 January 2021. A press release stated that a
recommendation on this could be issued by the agency by 29 January, with the European
Commission then making a decision on the CMA within days.[3] The Hungarian regulator unilaterally
approved the vaccine instead of waiting for EMA approval.[124]
On 29 January 2021, the EMA recommended granting a conditional marketing authorisation for
AZD1222 for people 18 years of age and older,[12][13] and the recommendation was accepted by
the European Commission the same day.[14][125]
On 30 January 2021, the Vietnamese Ministry of Health approved the AstraZeneca vaccine for
domestic inoculation, the first to be approved in Vietnam.[126]
The vaccine has also been approved by Argentina,[127] Bangladesh,[128] Brazil,[129] the Dominican
Republic,[90] El Salvador,[130] India,[131][132] Malaysia,[133] Mexico,[134] Nepal,[135] Pakistan,[136] the Philippines,
[137]
 Sri Lanka,[138] and Taiwan[139] regulatory authorities for emergency usage in their respective
countries.
On 7 February 2021, the vaccine roll out in South Africa was suspended. Researchers from
the University of the Witwatersrand said in a prior-to-peer analysis that the AstraZeneca vaccine
provided minimal protection against mild or moderate disease infection among young people.[140]
[141]
 The BBC reported on 8 February 2021 that Katherine O'Brien, director of immunisation at
the World Health Organization, indicated she felt it was "really plausible" the AstraZeneca vaccine
could have a "meaningful impact" on the South African variant particularly in preventing serious
illness and death.[142] The same report also indicated the Deputy Chief Medical Officer for
England Jonathan Van-Tam said the (Witwatersrand) study did not change his opinion that the
AstraZeneca vaccine was "rather likely" to have an effect on severe disease from the South African
variant.[142]
On 10 February 2021, South Korea granted its first approval of a COVID-19 vaccine to AstraZeneca,
allowing the two-shot regimen to be administered to all adults, including the elderly. The approval
came with a warning, however, that consideration is needed when administering the vaccine to
individuals over 65 years of age due to limited data from that demographic in clinical trials.[143][144]
On 10 February 2021, the World Health Organization (WHO) issued interim guidance and
recommended the AstraZeneca vaccine for all adults, its Strategic Advisory Group of Experts also
having considered use where variants were present and concluded there was no need not to
recommend it.[145]
On 16 February 2021, the Australian Therapeutic Goods Administration (TGA) granted provisional
approval for COVID-19 Vaccine AstraZeneca.[9][1]
On 26 February 2021, the vaccine was authorized with terms and conditions by Health Canada.[146]

Suspensions[edit]
On 3 March 2021, Austria suspended the use of a batch of the vaccine after two persons
suffered blood clot related complications after vaccination that resulted in one death.[147] In total four
blood clot cases have been identified for the same batch of 1 million doses.[147] Although no causal
link with vaccination had yet been established,[148] several other countries, including Denmark,
[149]
 Norway,[149] Iceland,[149] Romania,[150] Bulgaria,[150] Ireland,[151] Italy,[148] Spain,[152] Germany,[153] Netherlan
ds[154] and Slovenia[155] also halted the vaccine rollout while awaiting for the European Medicines
Agency to finish a safety review. Indonesia is also halting their vaccine rollout awaiting more safety
reviews from World Health Organization.[156]
On 11 March 2021 the European Medicines Agency stated that there was no indication that
vaccination had caused blood clots, which are not listed as side effects with the vaccine.[147]
[30]
 According to the EMA, the number of thromboembolic events in vaccinated people is no higher
than that seen in the general population.[30] As of 11 March 2021, 30 cases of thromboembolic events
had been reported among the almost 5 million people vaccinated in the European Economic Area.
[30]
 The Medicines and Healthcare products Regulatory Agency of the UK has also stated that after
more than 11 million doses administered it had not been confirmed that the reports of blood clots
were caused by the vaccine and that vaccinations would not be stopped.[31] On 12 March 2021
the World Health Organization stated that a causal relationship had not been shown and that
vaccinations should continue.[157]
On 14 March 2021, AstraZeneca has confirmed that after over 17 million people have been
vaccinated in the European Union and UK there has been no evidence of an increased risk of blood
clots in any particular country.[32] The company reported that as of 8 March 2021 across the EU and
UK, there have been 15 events of deep vein thrombosis and 22 events of pulmonary
embolism reported among those given the vaccine, which is much lower than would be expected to
occur naturally in a general population of that size.[32]
On 15 March 2021 the German Paul-Ehrlich Institute reported that out of 1.6 million vaccinations
seven cases of cerebral vein thrombosis in conjunction with a deficiency of blood platelets had
occurred.[158] According to the PEI, the number of cases of cerebral vein thrombosis after vaccination
was statistically significantly higher than the number of cases that would occur in the general
population during a similar time period.[158] These reports prompted the PEI to recommended a
temporary suspension of vaccinations until the EMA has completed their review of the cases.[159]

Safety profile[edit]
As of 28 February 2021 the MHRA said that over 9 million Oxford–AstraZeneca vaccinations had
been given. Around 10% of recipients experience adverse effects, mostly mild in nature, including
"injection site tenderness, injection-site pain, headache, fatigue, myalgia, malaise, pyrexia (fever),
chills, arthralgia, and nausea". 194 cases of anaphylaxis had been reported. Across all COVID-19
vaccines types, incidences of Bell's palsy in vaccine recipients were no higher than would be
expected naturally. 275 people, mostly the elderly or infirm, had died shortly after vaccination, but
this figure was consistent with an expected coincidental death rate, with no suggestion of a causal
link.[24]
In March 2021, countless European countries suspended the usage of the vaccines due to blood
clots, some even died from it. Italy decided to further investigate after a few deaths to determine if
there’s a link. The usual statement is that there is no direct link between the vaccines and the cause
of deaths or adverse side effects. The same statement was shared in India for Covishield, another
name for the same vaccine, as and when any incident occurred. The advantages outweigh the
disadvantages; you’re are protected against Covid-19.

Production and supply[edit]

The vaccine is stable at refrigerator temperatures and costs around US$3 to US$4 per dose.[160] On
17 December, a tweet by the Belgian Budget State Secretary revealed the European Union (EU)
would pay €1.78 (US$2.16) per dose.[161]
According to AstraZeneca's vice-president for operations and IT, Pam Cheng, the company would
have around 200 million doses ready worldwide by the end of 2020, and capacity to produce
100 million to 200 million doses per month once production is ramped up.[58]
In June 2020, further to making 100 million doses available to the UK's NHS for their vaccination
programme,[162] AstraZeneca and Emergent BioSolutions signed a US$87 million deal to manufacture
doses of the vaccine specifically for the US market. The deal was part of the Trump
administration's Operation Warp Speed initiative to develop and rapidly scale production of targeted
vaccines before the end of 2020.[163] Catalent will be responsible for the finishing and packaging
process.[164] The majority of manufacturing work will be done in the UK.[citation needed]
On 4 June 2020, the World Health Organization's (WHO) COVAX (COVID-19 Vaccines Global
Access) facility made initial purchases of 300 million doses from the company for low- to middle-
income countries.[165] Also, AstraZeneca and Serum Institute of India reached a licensing agreement
to supply 1 billion doses of the Oxford University vaccine to middle- and low-income countries,
including India.[166][167]
On 29 September 2020, a grant from the Bill and Melinda Gates Foundation allowed COVAX to
secure an additional 100 million COVID-19 vaccine doses either from AstraZeneca or from Novavax
at US$3 per dose.[168]
On 13 June 2020, AstraZeneca signed a contract with the Inclusive Vaccines Alliance, a group
formed by France, Germany, Italy, and the Netherlands, to supply up to 400 million doses to all
European Union member states.[169][170][171] However, the European Commission intervened to stop the
deal being formalised. It took over negotiations on behalf of the whole EU, signing a deal at the end
of August.[172]
In August 2020, AstraZeneca agreed to provide 300 million doses to the USA for US$1.2 billion,
implying a cost of US$4 per dose. An AstraZeneca spokesman said the funding also covers
development and clinical testing.[173] It also reached technology transfer agreement with Mexican and
Argentinean governments and agreed to produce at least 400 million doses to be distributed
throughout Latin America. The active ingredients would be produced in Argentina and sent to Mexico
to be completed for distribution.[174]
In September 2020, AstraZeneca agreed to provide 20 million doses to Canada.[175][176]
In October 2020, Switzerland signed an agreement with AstraZeneca to pre-order up to 5.3 million
doses.[177][178]
On 5 November 2020, a tripartite agreement was signed between the government of Bangladesh,
Serum Institute of India and Beximco Pharma of Bangladesh. Under the agreement Bangladesh
ordered 30 million doses of Oxford–AstraZeneca vaccine from Serum through Beximco for $4 per
shot.[179]
In November 2020, Thailand ordered 26 million doses of vaccine from AstraZeneca.[180] It would cover
13 million people,[181] approximately 20% of the population, with the first lot expected to be delivered
at the end of May.[182][183][184] The public health minister indicated the price paid was $5 per dose;
[185]
 AstraZeneca (Thailand) explained in January 2021 after a controversy that the price each country
paid depended on production cost and differences in supply chain, including manufacturing capacity,
labour and raw material costs.[186] In January 2021, the Thai cabinet approved further talks on
ordering another 35 million doses[187] and the Thai FDA approved the vaccine for emergency use for
1 year.[188][189] Siam Bioscience, a company owned by Vajiralongkorn, will received technological
transfer,[190] and has the capacity to manufacture up to 200 million doses a year for export to ASEAN.
[191]

Also in November, the Philippines agreed to buy 2.6 million doses,[192] reportedly worth around

₱700 million (approximately $5.6/dose).[193]
In December 2020, South Korea signed a contract with AstraZeneca to secure 20 million doses of its
vaccine, reportedly worth equivalently to those signed by Thailand and the Philippines,[194] with the
first shipment expected as early as January 2021. As of January 2021, the vaccine remains under
review by the South Korea Disease Control and Prevention Agency.[195][196] AstraZeneca signed a deal
with South Korea's SK Bioscience to manufacture its vaccine products. The collaboration calls for
the SK affiliate to manufacture AZD1222 for local and global markets.[197]
On 7 January 2021, the South African government announced that they had secured an initial
1 million doses from the Serum Institute of India, to be followed by another 500,000 doses in
February.[198]
Myanmar signed a contract with Serum Institute of India to secure 30 million doses of its vaccine in
December 2020. Myanmar will get doses for 15 million people from February 2021.[199]
On 22 January 2021, AstraZeneca announced that in the event the European Union approved the
COVID-19 Vaccine AstraZeneca, initial supplies would be lower than expected due to production
issues at Novasep in Belgium. Only 31 million of the previously predicted 80 million doses would be
delivered to the European Union by March 2021.[200] In an interview with Italian newspaper La
Repubblica, AstraZeneca's CEO Pascal Soriot said the delivery schedule for the doses in the
European Union was two months behind schedule. He mentioned low yield from cell cultures in one
large-scale European site.[201] Analysis published in The Guardian also identified an apparently low
yield from bioreactors in the Belgium plant and noted the difficulties in setting up this form of
process, with variable yields often occurring.[202] As a result, the European Union imposed export
controls on vaccine doses; controversy erupted as to whether doses were being diverted to the UK,
and whether or not deliveries to Northern Ireland would be disrupted.[203]
On 24 February 2021, a shipment of the vaccine to Accra, Ghana via COVAX made it the first
country in Africa to receive vaccines via the initiative.[204]