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The Oxford–AstraZeneca COVID19 vaccine, sold under the brand names Covishield and Vaxzevria
among others, is a
viral vector vaccine
A viral vector vaccine is a vaccine that uses a viral vector to deliver genetic material ( DNA), which can be transcribed by the recipient's host cells as mRNA coding for a desired protein (or: antigen) to elicit an immune response. , six viral v ...
for prevention of COVID-19. Developed in the United Kingdom by
Oxford University
Oxford () is a city in England. It is the county town and only city of Oxfordshire. In 2020, its population was estimated at 151,584. It is north-west of London, south-east of Birmingham and north-east of Bristol. The city is home to the ...
and British-Swedish company
AstraZeneca
AstraZeneca plc () is a British-Swedish multinational pharmaceutical and biotechnology company with its headquarters at the Cambridge Biomedical Campus in Cambridge, England. It has a portfolio of products for major diseases in areas includin ...
,
using as a vector the modified chimpanzee
adenovirus ChAdOx1
ChAdOx1 is an adenoviral vector for vaccines that was developed by the Jenner Institute, University of Oxford. The vector is a chimpanzee adenovirus modified to avoid its replication.
Adenoviruses are effective vectors for inducing and boostin ...
.
The vaccine is given by
intramuscular injection
Intramuscular injection, often abbreviated IM, is the injection of a substance into a muscle. In medicine, it is one of several methods for parenteral administration of medications. Intramuscular injection may be preferred because muscles have ...
. 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
The Alpha variant (B.1.1.7) was a SARS-CoV-2 variant of concern. It was estimated to be 40–80% more transmissible than the wild-type SARS-CoV-2 (with most estimates occupying the middle to higher end of this range). It was first detecte ...
(lineage B.1.1.7), and 61% against the
Delta variant
The Delta variant (B.1.617.2) was a variant of SARS-CoV-2, the virus that causes COVID-19. It was first detected in India in late 2020. The Delta variant was named on 31 May 2021 and had spread to over 179 countries by 22 November 2021. The ...
(lineage B.1.617.2).
The vaccine is stable at refrigerator temperatures and has a good safety profile, with
side effect
In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...
s including injection-site pain, headache, and nausea, all generally resolving within a few days.
More rarely, anaphylaxis
Anaphylaxis is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of use of emergency medication on site. It typically causes more than one of the follow ...
may occur; the UK Medicines and Healthcare products Regulatory Agency (MHRA) has 268 reports out of some 21.2million vaccinations . 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
Post-vaccination embolic and thrombotic events, termed vaccine-induced immune thrombotic thrombocytopenia (VITT), vaccine-induced prothrombotic immune thrombocytopenia (VIPIT), thrombosis with thrombocytopenia syndrome (TTS), vaccine-induced imm ...
). According to the European Medicines Agency
The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Euro ...
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
The European Economic Area (EEA) was established via the ''Agreement on the European Economic Area'', an international agreement which enables the extension of the European Union's single market to member states of the European Free Trade Ass ...
(a percentage of 0.0007%).[ Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.]
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
The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Euro ...
(EMA), and the Australian Therapeutic Goods Administration
The Therapeutic Goods Administration (TGA) is the medicine and therapeutic regulatory agency of the Australian Government. As part of the Department of Health and Aged Care, the TGA regulates the quality, supply and advertising of medicines, pa ...
(provisional approval in February 2021), and was approved for an Emergency Use Listing by the World Health Organization
The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...
(WHO). , more than 2.5billion doses of the vaccine have been released to more than 170 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.
Medical uses
The Oxford–AstraZeneca COVID19 vaccine is used to provide protection against infection by the SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is a strain of coronavirus that causes COVID-19 (coronavirus disease 2019), the respiratory illness responsible for the ongoing COVID-19 pandemic. The virus previously had a ...
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
Intramuscular injection, often abbreviated IM, is the injection of a substance into a muscle. In medicine, it is one of several methods for parenteral administration of medications. Intramuscular injection may be preferred because muscles have ...
into the deltoid muscle
The deltoid muscle is the muscle forming the rounded contour of the human shoulder. It is also known as the 'common shoulder muscle', particularly in other animals such as the domestic cat. Anatomically, the deltoid muscle appears to be made up o ...
(upper arm). The initial course consists of two doses with an interval of 4 to 12 weeks between doses. The World Health Organization
The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...
(WHO) recommends an interval of 8 to 12 weeks between doses for optimal efficacy.
, there is no evidence that a third booster dose
A booster dose is an extra administration of a vaccine after an earlier (primer) dose. After initial immunization, a booster provides a re-exposure to the immunizing antigen. It is intended to increase immunity against that antigen back to protec ...
dose is needed to prevent severe disease in healthy adults.
Effectiveness
Preliminary data from a study in Brazil with 61 million individuals from 18 January to 30 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 or older, attributable to immunosenescence
Immunosenescence is the gradual deterioration of the immune system, brought on by natural age advancement. A 2020 review concluded that the adaptive immune system is affected more than the innate immune system. Immunosenescence involves both the ...
.
A vaccine is generally considered effective if the estimate is ≥50% with a >30% lower limit of the 95% confidence interval
In frequentist statistics, a confidence interval (CI) is a range of estimates for an unknown parameter. A confidence interval is computed at a designated ''confidence level''; the 95% confidence level is most common, but other levels, such as 9 ...
. Effectiveness is generally expected to slowly decrease over time.
Preliminary data suggest that the initial two-dose regimen is not effective against symptomatic disease caused by the Omicron variant
Omicron (B.1.1.529) is a variant of SARS-CoV-2 first reported to the World Health Organization (WHO) by the Network for Genomics Surveillance in South Africa on 24 November 2021. It was first detected in Botswana and has spread to become the ...
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
Moderna, Inc. ( ) is an American pharmaceutical and biotechnology company based in Cambridge, Massachusetts that focuses on RNA therapeutics, primarily mRNA vaccines. These vaccines use a copy of a molecule called messenger RNA (mRNA) to pro ...
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
Capillary leak syndrome, or vascular leak syndrome, is characterized by the escape of blood plasma through capillary walls, from the blood circulatory system to surrounding tissues, muscle compartments, organs or body cavities. It is a phenomenon ...
.
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 (TTS) has been associated with mainly younger female recipients of the vaccine. Analysis of VigiBase
VigiBase is a World Health Organization's (WHO) global Individual Case Safety Report (ICSR) database that contains ICSRs submitted by the participating member states enrolled under WHO's international drug monitoring programme. It is the single lar ...
reported embolic and thrombotic events after vaccination with Oxford–AstraZeneca, Moderna
Moderna, Inc. ( ) is an American pharmaceutical and biotechnology company based in Cambridge, Massachusetts that focuses on RNA therapeutics, primarily mRNA vaccines. These vaccines use a copy of a molecule called messenger RNA (mRNA) to pro ...
and Pfizer
Pfizer Inc. ( ) is an American multinational pharmaceutical and biotechnology corporation headquartered on 42nd Street in Manhattan, New York City. The company was established in 1849 in New York by two German entrepreneurs, Charles Pfizer ...
vaccines, found a temporally related incidence of 0.21 cases per 1 million vaccinated-days.
Anaphylaxis
Anaphylaxis is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of use of emergency medication on site. It typically causes more than one of the follow ...
and other allergic reactions are known side effects of the Oxford–AstraZeneca COVID-19 vaccine. The European Medicines Agency
The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Euro ...
(EMA) has assessed 41 cases of anaphylaxis
Anaphylaxis is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of use of emergency medication on site. It typically causes more than one of the follow ...
from around 5million vaccinations in the United Kingdom.
Capillary leak syndrome
Capillary leak syndrome, or vascular leak syndrome, is characterized by the escape of blood plasma through capillary walls, from the blood circulatory system to surrounding tissues, muscle compartments, organs or body cavities. It is a phenomenon ...
is a possible side effect of the vaccine.
The European Medicines Agency
The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Euro ...
(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.
Additional side effects include tinnitus
Tinnitus is the perception of sound when no corresponding external sound is present. Nearly everyone experiences a faint "normal tinnitus" in a completely quiet room; but it is of concern only if it is bothersome, interferes with normal hearin ...
(persistent ringing in the ears), paraesthesia
Paresthesia is an abnormal sensation of the skin (tingling, pricking, chilling, burning, numbness) with no apparent physical cause. Paresthesia may be transient or chronic, and may have any of dozens of possible underlying causes. Paresthesias ar ...
(unusual feeling in the skin, such as tingling or a crawling sensation), and hypoaesthesia (decreased feeling or sensitivity, especially in the skin).
Pharmacology
The Oxford–AstraZeneca COVID-19 vaccine is a viral vector
Viral vectors are tools commonly used by molecular biologists to deliver genetic material into cells. This process can be performed inside a living organism (''in vivo'') or in cell culture (''in vitro''). Viruses have evolved specialized molecul ...
vaccine containing a modified, replication-deficient chimpanzee adenovirus ChAdOx1
ChAdOx1 is an adenoviral vector for vaccines that was developed by the Jenner Institute, University of Oxford. The vector is a chimpanzee adenovirus modified to avoid its replication.
Adenoviruses are effective vectors for inducing and boostin ...
, containing the full‐length codon‐optimised coding sequence of SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is a strain of coronavirus that causes COVID-19 (coronavirus disease 2019), the respiratory illness responsible for the ongoing COVID-19 pandemic. The virus previously had a ...
spike protein
In virology, a spike protein or peplomer protein is a protein that forms a large structure known as a spike or peplomer projecting from the surface of an enveloped virus. as cited in The proteins are usually glycoproteins that form dimers or ...
along with a tissue plasminogen activator
Tissue plasminogen activator (abbreviated tPA or PLAT) is a protein involved in the breakdown of blood clots. It is a serine protease () found on endothelial cells, the cells that line the blood vessels. As an enzyme, it catalyzes the conversion ...
(tPA) 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
Human embryonic kidney 293 cells, also often referred to as HEK 293, HEK-293, 293 cells, or less precisely as HEK cells, are a specific immortalised cell line derived from a spontaneously miscarried or aborted fetus or human embryonic kidney cells ...
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
The cell nucleus (pl. nuclei; from Latin or , meaning ''kernel'' or ''seed'') is a membrane-bound organelle found in eukaryotic cells. Eukaryotic cells usually have a single nucleus, but a few cell types, such as mammalian red blood cells, h ...
; thereafter, the cell's machinery does the transcription
Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including:
Genetics
* Transcription (biology), the copying of DNA into RNA, the fir ...
from DNA into mRNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein.
mRNA is ...
and the translation
Translation is the communication of the Meaning (linguistic), meaning of a #Source and target languages, source-language text by means of an Dynamic and formal equivalence, equivalent #Source and target languages, target-language text. The ...
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
Sputnik V (russian: Спутник V, the brand name from RDIF) or Gam-COVID-Vac (russian: Гам-КОВИД-Вак, the name under which it is legally registered and produced) is an adenovirus viral vector vaccine for COVID-19 developed by ...
.
The protein of interest is the spike protein
In virology, a spike protein or peplomer protein is a protein that forms a large structure known as a spike or peplomer projecting from the surface of an enveloped virus. as cited in The proteins are usually glycoproteins that form dimers or ...
, a protein on the exterior of the virus that enables SARS-type coronaviruses to enter cells through the ACE2
Angiotensin-converting enzyme 2 (ACE2) is an enzyme that can be found either attached to the membrane of cells (mACE2) in the intestines, kidney, testis, gallbladder, and heart or in a soluble form (sACE2). Both membrane bound and soluble ACE2 a ...
receptor. Following vaccination, the production of coronavirus spike protein within the body will cause the immune system to attack the spike protein with antibodies
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
and T-cells
A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell r ...
if the virus later enters the body.
Manufacturing
To manufacture the vaccine the virus is propagated on HEK 293
Human embryonic kidney 293 cells, also often referred to as HEK 293, HEK-293, 293 cells, or less precisely as HEK cells, are a specific immortalised cell line derived from a spontaneously miscarried or aborted fetus or human embryonic kidney cells ...
cell lines
An immortalised cell line is a population of cells from a multicellular organism which would normally not proliferate indefinitely but, due to mutation, have evaded normal cellular senescence and instead can keep undergoing division. The cells ...
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 (EU) would pay () per dose, ''The New York Times
''The New York Times'' (''the Times'', ''NYT'', or the Gray Lady) is a daily newspaper based in New York City with a worldwide readership reported in 2020 to comprise a declining 840,000 paid print subscribers, and a growing 6 million paid ...
'' suggesting the lower price might relate to factors including investment in vaccine production infrastructure by the EU.
the vaccine active substance (ChAdOx1-SARS-COV-2) is being produced at several sites worldwide, with AstraZeneca claiming to have established 25 sites in 15 countries. The UK sites are Oxford
Oxford () is a city in England. It is the county town and only city of Oxfordshire. In 2020, its population was estimated at 151,584. It is north-west of London, south-east of Birmingham and north-east of Bristol. The city is home to the ...
and Keele
Keele is a village and civil parish in the Borough of Newcastle-under-Lyme in Staffordshire, England. It is approximately three miles (5 km) west of Newcastle-under-Lyme, and is close to the village of Silverdale. Keele lies on the A53 ro ...
with bottling and finishing in Wrexham
Wrexham ( ; cy, Wrecsam; ) is a city and the administrative centre of Wrexham County Borough in Wales. It is located between the Welsh mountains and the lower Dee Valley, near the border with Cheshire in England. Historically in the count ...
. Other sites include the Serum Institute of India
Serum Institute of India (SII) is an Indian biotechnology and biopharmaceuticals company, based in Pune. It is the world's largest manufacturer of vaccines. It was founded by Cyrus Poonawalla in 1966 and is a part of Cyrus Poonawalla Group.
...
at Pune
Pune (; ; also known as Poona, (List of renamed Indian cities and states#Maharashtra, the official name from 1818 until 1978) is one of the most important industrial and educational hubs of India, with an estimated population of 7.4 million ...
. The Halix site at Leiden
Leiden (; in English and archaic Dutch also Leyden) is a city and municipality in the province of South Holland, Netherlands. The municipality of Leiden has a population of 119,713, but the city forms one densely connected agglomeration wit ...
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
The Jenner Institute is a research institute on the Old Road Campus in Headington, east Oxford, England. It was formed in November 2005 through a partnership between the University of Oxford and the UK Institute for Animal Health. It is ass ...
and Vaccitech, a private company spun off from the university, with financing from Oxford Sciences Innovation
Oxford Sciences Enterprises is an early-stage venture capital firm with over $800M in AUM based in Oxford, UK. It operates in partnership with the University of Oxford, as the university's preferred investor, several prominent financiers back th ...
, Google Ventures
GV is a venture capital investment arm of Alphabet Inc., founded by Bill Maris, that provides Seed investment, seed, Venture capital financing, venture, and Growth investing, growth stage funding to technology companies. Founded as Google Venture ...
, and Sequoia Capital
Sequoia Capital is an American venture capital firm. The firm is headquartered in Menlo Park, California, and specializes in seed stage, early stage, and growth stage investments in private companies across technology sectors. , Sequoia's total a ...
, 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
The Oxford Vaccine Group (OVG) is a vaccine research group within the Department of Paediatrics at the University of Oxford. It was founded in 1994 by Professor E. Richard Moxon, was initially based at the John Radcliffe Hospital, and moved in ...
in collaboration with Italian manufacturer Advent Srl located in Pomezia
Pomezia () is a municipality (''comune'') in the Metropolitan City of Rome Capital, Lazio, central Italy. In 2009 it had a population of about 60,000.
History
The town was built entirely new near the location of ancient Lavinium on land resulting ...
. The team is led by Sarah Gilbert
Dame Sarah Catherine Gilbert (born April 1962) is an English vaccinologist who is a Professor of Vaccinology at the University of Oxford and co-founder of Vaccitech. She specialises in the development of vaccines against influenza and emergi ...
, 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
The Bill & Melinda Gates Foundation (BMGF), a merging of the William H. Gates Foundation and the Gates Learning Foundation, is an American private foundation founded by Bill Gates and Melinda French Gates. Based in Seattle, Washington, it was ...
urged Oxford to find a large company partner to get its COVID-19 vaccine to market, the university backed off of 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 (The Guardian
''The Guardian'' is a British daily newspaper. It was founded in 1821 as ''The Manchester Guardian'', and changed its name in 1959. Along with its sister papers ''The Observer'' and ''The Guardian Weekly'', ''The Guardian'' is part of the Gu ...
reported the initial partner was the German-based Merck Group
The Merck Group, branded and commonly known as Merck, is a German multinational science and technology company headquartered in Darmstadt, with about 60,000 employees and present in 66 countries. The group includes around 250 companies; the m ...
instead). 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
''The Wall Street Journal'' is an American business-focused, international daily newspaper based in New York City, with international editions also available in Chinese and Japanese. The ''Journal'', along with its Asian editions, is published ...
''. 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
The National Institute of Allergy and Infectious Diseases (NIAID, ) is one of the 27 institutes and centers that make up the National Institutes of Health (NIH), an agency of the United States Department of Health and Human Services (HHS). NIAID's ...
(NIAID) 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
GAVI, officially Gavi, the Vaccine Alliance (previously the GAVI Alliance, and before that the Global Alliance for Vaccines and Immunization) is a public–private global health partnership with the goal of increasing access to immunization ...
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.
Clinical trials
In July 2020, AstraZeneca partnered with IQVIA
IQVIA, formerly Quintiles and IMS Health, Inc., is an American multinational company serving the combined industries of health information technology and clinical research. IQVIA is a provider of biopharmaceutical development and commercial outs ...
to accelerate the timeframe for clinical trials being planned or conducted in the US. On 31 August, AstraZeneca announced that it had begun enrolment of adults for a US-funded, 30,000-subject late-stage study.
Clinical trials for the vaccine candidate were halted worldwide on 8 September, as AstraZeneca investigated a possible adverse reaction which occurred in a trial participant in the UK. Trials were resumed on 13 September after AstraZeneca and Oxford, along with UK regulators, concluded it was safe to do so. AstraZeneca was later criticised for refusing to provide details about potentially serious neurological side effects in two trial participants who had received the experimental vaccine in the UK. While the trials resumed in the UK, Brazil, South Africa, Japan and India, the US did not resume clinical trials of the vaccine until 23 October. This was due to a separate investigation by the Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
surrounding a patient illness that triggered a clinical hold, according to the US Department of Health and Human Services
The United States Department of Health and Human Services (HHS) is a cabinet-level executive branch department of the U.S. federal government created to protect the health of all Americans and providing essential human services. Its motto is ...
(HHS) Secretary Alex Azar
Alex Michael Azar II (; born June 17, 1967) is an American attorney, businessman, lobbyist, and former pharmaceutical executive who served as the United States secretary of health and human services from 2018 to 2021. Azar was nominated to his p ...
.
The results of the COV002 phase II/III trial showed that immunity lasts for at least one year after a single dose.
Results of Phase III trial
On 23 November 2020, the first interim data was released by Oxford University and AstraZeneca from the vaccine's ongoing Phase III trials
The phases of clinical research are the stages in which scientists conduct experiments with a health intervention to obtain sufficient evidence for a process considered effective as a medical treatment. For drug development, the clinical phases ...
. The interim data reported a 70% efficacy, based on combined results of 62% and 90% from different groups of participants who were given different dosages. The decision to combine results from two different dosages was met with criticism from some who questioned why the results were being combined. AstraZeneca responded to the criticism by agreeing to carry out a new multi-country trial using the lower dose, which had led to the 90% claim.
The full publication of the interim results from four ongoing Phase III trials on 8 December allowed regulators and scientists to begin evaluating the vaccine's efficacy. The December report showed that at 21 days after the second dose and beyond, there were no hospitalisations or severe disease in those who received the vaccine, compared to 10 cases in the control groups. The rate of serious adverse events was balanced between the active and control groups, which suggested that the active vaccine did not pose safety concerns beyond a rate experienced in the general population. One case of transverse myelitis
Transverse myelitis (TM) is a rare neurological condition wherein the spinal cord is Inflammation, inflamed. The adjective ''wikt:transverse#Adjective, transverse'' implies that the spinal inflammation (myelitis) extends horizontally throughout ...
was reported 14 days after the second-dose was administered as being possibly related to vaccination, with an independent neurological committee considering the most likely diagnosis to be of an idiopathic
An idiopathic disease is any disease with an unknown cause or mechanism of apparent wikt:spontaneous, spontaneous origin. From Ancient Greek, Greek ἴδιος ''idios'' "one's own" and πάθος ''pathos'' "suffering", ''idiopathy'' means approxi ...
, short-segment, spinal cord demyelination
A demyelinating disease is any disease of the nervous system in which the myelin sheath of neurons is damaged. This damage impairs the conduction of signals in the affected nerves. In turn, the reduction in conduction ability causes deficiency i ...
. 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.
A subsequent analysis, published on 19 February 2021, showed an efficacy of 76.0% at preventing symptomatic COVID-19 beginning at 22 days following the first dose, increasing to 81.3% when the second dose is given 12 weeks or more after the first. However, the results did not show any protection against asymptomatic COVID-19 following only one dose. Beginning 14 days following timely administration of a second dose, with different duration from the first dose depending on trials, the results showed 66.7% efficacy at preventing symptomatic infection, and the UK arm (which evaluated asymptomatic infections in participants) was inconclusive as to the prevention of asymptomatic infection. Efficacy was higher at greater intervals between doses, peaking at around 80% when the second dose was given at 12 weeks or longer after the first. Preliminary results from another study with 120 participants under 55 years of age showed that delaying the second dose by up to 45 weeks increases the resulting immune response and that a booster
Booster may refer to:
Amusement rides
* Booster (Fabbri ride), a pendulum ride
* Booster (HUSS ride), an evolution of the Breakdance ride
* Booster (KMG ride), a pendulum ride
Arts, entertainment, and media Fictional characters
* Booster, a cha ...
(third) dose given at least six months later produces a strong immune response. A booster dose may not be necessary, but it alleviates concerns that the body would develop immunity to the vaccine's viral vector, which would reduce the potency of annual inoculations.
On 22 March 2021, AstraZeneca released interim results from the phase III trial conducted in the US that showed efficacy of 79% at preventing symptomatic COVID-19 and 100% efficacy at preventing severe disease and hospitalisation. The next day, the National Institute of Allergy and Infectious Diseases
The National Institute of Allergy and Infectious Diseases (NIAID, ) is one of the 27 institutes and centers that make up the National Institutes of Health (NIH), an agency of the United States Department of Health and Human Services (HHS). NIAID's ...
(NIAID) published a statement countering that those results may have relied on "outdated information" that may have provided an incomplete view of the efficacy data. AstraZeneca later revised its efficacy claim to be 76% after further review of the data. On 29 September 2021, AstraZeneca shows of 74% efficacy rate in the US trial.
Single dose effectiveness
A study on the effectiveness of a first dose of the Pfizer–BioNTech or Oxford–AstraZeneca COVID-19 vaccines against COVID-19 related hospitalisation in Scotland was based on a national prospective cohort study of 5.4million people. Between 8 December 2020 and 15 February 2021, 1,137,775 participants were vaccinated in the study, 490,000 of whom were given 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. Combined results (all vaccinated participants, whether Pfizer–BioNTech or Oxford–AstraZeneca) showed a significant 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 participants over the age of 65 were given the Oxford–AstraZeneca vaccine.
Nasal spray
On 25 March 2021, the University of Oxford announced the start of a phase I clinical trial to investigate the efficacy of an intranasal spray method.
Approvals
The first country to issue a temporary or emergency approval for the Oxford–AstraZeneca vaccine was the UK. The Medicines and Healthcare products Regulatory Agency (MHRA) began a review of efficacy and safety data on 27 November 2020, followed by approval for use on 30 December 2020, becoming the second vaccine approved for use in the national vaccination programme. The BBC reported that the first person to receive the vaccine outside of clinical trials was vaccinated on 4 January 2021.
The European Medicines Agency
The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Euro ...
(EMA) began review of the vaccine on 12 January 2021, and stated in a press release that a recommendation could be issued by the agency by 29 January, followed by the European Commission deciding on a conditional marketing authorisation within days. On 29 January 2021, the EMA recommended granting a conditional marketing authorisation for AZD1222 for people 18 years of age and older, and the recommendation was accepted by the European Commission
The European Commission (EC) is the executive of the European Union (EU). It operates as a cabinet government, with 27 members of the Commission (informally known as "Commissioners") headed by a President. It includes an administrative body o ...
the same day. Prior to approval across the EU, the Hungarian regulator unilaterally approved the vaccine instead of waiting for EMA approval. In October 2022, the conditional marketing authorisation was converted to a standard one.
On 30 January 2021, the Vietnamese Ministry of Health approved the AstraZeneca vaccine for use, becoming the first vaccine to be approved in Vietnam
Vietnam or Viet Nam ( vi, Việt Nam, ), officially the Socialist Republic of Vietnam,., group="n" is a country in Southeast Asia, at the eastern edge of mainland Southeast Asia, with an area of and population of 96 million, making i ...
. The vaccine has since been approved by a number of non-EU countries, including Argentina, Bangladesh, Brazil, the Dominican Republic, El Salvador, India, Israel, Malaysia, Mexico, Nepal, Pakistan, the Philippines, Sri Lanka, and Taiwan regulatory authorities for emergency usage in their respective countries.
South Korea
South Korea, officially the Republic of Korea (ROK), is a country in East Asia, constituting the southern part of the Korea, Korean Peninsula and sharing a Korean Demilitarized Zone, land border with North Korea. Its western border is formed ...
granted approval of the AstraZeneca vaccine on 10 February 2021, thus becoming the first vaccine to be approved for use in that country. The regulator recommended the two-shot regimen be used in all adults, including the elderly, noting 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. On the same day, the World Health Organization
The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...
(WHO) issued interim guidance and recommended the AstraZeneca vaccine for all adults, its Strategic Advisory Group of Experts The Strategic Advisory Group of Experts (SAGE) is the principal advisory group to World Health Organization (WHO) for vaccines and immunization. Established in 1999 through the merging of two previous committees, notably the Scientific Advisory Grou ...
also having considered use where variants were present and concluded there was no need not to recommend it.
In February 2021, the government and regulatory authorities in Australia (16 February 2021) and Canada (26 February 2021) granted approval for temporary use of the vaccine.
On 19 November 2021, the vaccine was approved for use in Canada.
Suspensions
South Africa
On 7 February 2021, the vaccine rollout in South Africa was suspended. Researchers from the University of the Witwatersrand
The University of the Witwatersrand, Johannesburg (), is a multi-campus South African Public university, public research university situated in the northern areas of central Johannesburg. It is more commonly known as Wits University or Wits ( o ...
released interim, non-peer-reviewed data that suggested the AstraZeneca vaccine provided minimal protection against mild or moderate disease infection among young people. The BBC #REDIRECT BBC #REDIRECT BBC
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reported on 8 February 2021 that
Katherine O'Brien, director of immunisation at the WHO, felt it was "really plausible" the AstraZeneca vaccine could have a "meaningful impact" on the
Beta variant
The Beta variant, (B.1.351), was a variant of SARS-CoV-2, the virus that causes COVID-19. One of several SARS-CoV-2 variants initially believed to be of particular importance, it was first detected in the Nelson Mandela Bay metropolitan are ...
(lineage B.1.351), particularly in preventing serious illness and death.
The same report also indicated the Deputy
Chief Medical Officer for England
In the United Kingdom, a Chief Medical Officer (CMO) is the most senior government advisor on matter relating to health. There are four CMOs in the United Kingdom who are appointed to advise their respective governments:
* His Majesty's Governm ...
Jonathan Van-Tam
Sir Jonathan Stafford Nguyen-Van-Tam (born 2 February 1964) is a British healthcare professional specialising in influenza, including its epidemiology, transmission, vaccinology, antiviral drugs and pandemic preparedness.
After hospital wor ...
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 Beta variant.
The South African government subsequently cancelled the use of the AstraZeneca vaccine.
European Union
On 3 March 2021, Austria suspended the use of one batch of vaccine after two people had
blood clot
A thrombus (plural thrombi), colloquially called a blood clot, is the final product of the blood coagulation step in hemostasis. There are two components to a thrombus: aggregated platelets and red blood cells that form a plug, and a mesh of ...
s after vaccination, one of whom died.
In total, four cases of blood clots have been identified in the same batch of 1million doses.
Although no causal link with vaccination has been shown,
several other countries, including Denmark,
Norway,
Iceland,
Bulgaria,
Ireland, Italy,
Spain, Germany, France, the Netherlands and Slovenia also halted the vaccine rollout over the following days while waiting for the EMA to finish a safety review triggered by the cases.
In April 2021, the EMA concluded its safety review and concluded that unusual blood clots with low blood platelets should be listed as very rare side effects while reaffirming the overall benefits of the vaccine.
Following this announcement EU countries have resumed use of the vaccine with some limiting its use to elderly people at higher risk for severe COVID-19 illness.
On 11 March 2021, the
Norwegian government
The politics of Norway take place in the framework of a parliamentary, representative democratic constitutional monarchy. Executive power is exercised by the Council of State, the cabinet, led by the prime minister of Norway. Legislative power is ...
temporarily suspended the vaccine's use, awaiting more information regarding potential adverse effects. Then, on 15 April, the
Norwegian Institute of Public Health
The Norwegian Institute of Public Health (NIPH) (Norwegian: ''Folkehelseinstituttet''; FHI) is a Norwegian government agency and research institute, and is Norway's national public health institute. It is subordinate to the Ministry of Health and ...
recommended to the government to permanently suspended vaccination with AstraZeneca due to the "rare but severe incidents with low platelet counts, blood clots, and haemorrhages," since in the case of Norway, "the risk of dying after vaccination with the AstraZeneca vaccine would be higher than the risk of dying from the disease, particularly for younger people."
At the same time, the Norwegian government announced their decision to wait for a final decision and to establish an expert group to provide a broader assessment on the safety of the AstraZeneca and Janssen vaccines. On 10 May, the expert committee also recommended suspending the use of both vaccines. Finally, on 12 May —two months after the initial suspension— the
Prime Minister of Norway
The prime minister of Norway ( no, statsminister, which directly translates to "minister of state") is the head of government and chief executive of Norway. The prime minister and Cabinet (consisting of all the most senior government department ...
announced that the government decided to completely remove the AstraZeneca vaccine from the Norwegian Coronavirus Immunisation Programme, and people who have had the first will be offered another coronavirus vaccine for their second dose.
On 30 March 2021, the German Ministry of Health announced that the use of the vaccine in people aged 60 and below should be the result of a recipient-specific discussion,
and that younger patients could still be given the AstraZeneca vaccine, but only "at the discretion of doctors, and after individual risk analysis and thorough explanation".
On 14 April, the
Danish Health Authority suspended use of the vaccine.
The Danish Health Authority said that it had other vaccines available, and that the next target groups being a lower-risk population had to be "
eighedagainst the fact that we now have a known risk of severe adverse effects from vaccination with AstraZeneca, even if the risk in absolute terms is slight."
A 2021 study found that the decisions to suspend the vaccine led to increased vaccine hesitancy across the West, even in countries that did not suspend the vaccine.
In October 2022, the conditional marketing authorisation was converted to a standard one.
Canada
On 29 March 2021, Canada's
National Advisory Committee on Immunization
The National Advisory Committee on Immunization (NACI; french: Comité consultatif national de l'immunisation; french: CCNI, label=none) is an advisory body that provides the Government of Canada with medical and scientific advice relating to h ...
(NACI) recommended that distribution of the vaccine be suspended for patients below the age of 55; NACI chairwoman
Caroline Quach-Thanh
Caroline Quach-Thanh (born March 15, 1972) is a Canadian pediatric microbiologist, epidemiologist and infectious diseases specialist. She is a professor in the Université de Montréal Faculty of Medicine and Medical Lead in the Infection Preven ...
stated that the risk of blood clots was higher in younger patients, and that NACI needed to "evolve" its recommendations as new data becomes available. Most Canadian provinces subsequently announced that they would follow this guidance. there had been three confirmed cases of blood clotting tied to the vaccine in Canada, out of over 700,000 doses administered in the country.
Beginning 18 April, amid a major third wave of the virus, several Canadian provinces announced that they would backtrack on the NACI recommendation and extend eligibility for the AstraZeneca vaccine to residents as young as 40 years old, including Alberta, British Columbia, Ontario, and Saskatchewan. Quebec also extended eligibility to residents 45 and older. The NACI guidance is a recommendation which does not affect the formal approval of the vaccine by
Health Canada for all adults over 18; it stated on 14 April that it had updated its warnings on the vaccine as part of an ongoing review, but that "the potential risk of these events is very rare, and the benefits of the vaccine in protecting against COVID-19 outweigh its potential risks."
On 23 April, citing the current state of supplies for mRNA-based vaccines and new data, NACI issued a recommendation that the vaccine can be offered to patients as young as 30 years old if benefits outweigh the risks, and the patient "does not wish to wait for an mRNA vaccine".
Beginning 11 May, multiple provinces announced that they would suspend use of the AstraZeneca vaccine once again, citing either supply issues or the blood clotting risk. Some provinces stated that they planned to only use the AstraZeneca vaccine for outstanding second doses. On 1 June, NACI issued guidance, citing the safety concerns as well as European studies showing an improved antibody response, recommending that an mRNA vaccine be administered as a second dose to patients that had received the AstraZeneca vaccine as their first dose.
Indonesia
In mid-March, Indonesia halted the rollout of the vaccine while awaiting more safety guidance from the World Health Organization,
and then resumed using the vaccine on 19 March.
Australia
On 17 June 2021, Australia revised its recommendations for the rollout of the vaccine, recommending that the Pfizer Comirnaty vaccine be used for people aged under 60 years if the person has not already received a first dose of AstraZeneca COVID-19 vaccine. The AstraZeneca COVID-19 vaccine can still be used in people aged under 60 years where the benefits are likely to outweigh the risks for that person, and the person has made an informed decision based on an understanding of the risks and benefits in consultation with a medical professional.
Malaysia
After initially approving the use of the AstraZeneca vaccine, Malaysian health authorities removed the vaccine from the country's mainstream vaccination programme due to public concerns about its safety. The AstraZeneca vaccines will be distributed in designated vaccination centres, and the public can register for the vaccine on a voluntary basis. All 268,800 doses of the initial batch of the vaccine were fully booked in three and a half hours after the registration opened for residents of the state of Selangor and the Federal Territory of Kuala Lumpur. A second batch of 1,261,000 doses was offered to residents of the states of Selangor, Penang, Johore, Sarawak, and the Federal Territory of Kuala Lumpur. A total of 29,183 doses were reserved for previously waitlisted registrants, and 275,208 doses were taken up by senior citizens during a grace 3-day period. The remaining 956,609 doses were then offered to those aged 18 and above, and was completely booked within an hour.
Safety review
On 11 March 2021, the
European Medicines Agency
The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Euro ...
(EMA) stated that there is no indication that vaccination has been the cause of the observed clotting issues, which were not listed as side effects of the vaccine.
At the time, according to the EMA, the number of
thromboembolic
Thrombosis (from Ancient Greek "clotting") is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (thr ...
events in vaccinated people was no higher than that seen in the general population.
, 30 cases of thromboembolic events had been reported among the almost 5million people vaccinated in the European Economic Area.
The UK's MHRA also stated that after more than 11million doses administered, it had not been confirmed that the reported blood clots were caused by the vaccine and that vaccinations would not be stopped.
On 12 March 2021 the WHO stated that a causal relationship had not been shown and that vaccinations should continue. AstraZeneca confirmed on 14 March 2021 that after examining over 17million people who have been vaccinated with the vaccine, no evidence of an increased risk of blood clots in any particular country was found.
The company reported that , across the EU and UK, there had been 15 events of
deep vein thrombosis
Deep vein thrombosis (DVT) is a type of venous thrombosis involving the formation of a blood clot in a deep vein, most commonly in the legs or pelvis. A minority of DVTs occur in the arms. Symptoms can include pain, swelling, redness, and enla ...
and 22 events of
pulmonary embolism
Pulmonary embolism (PE) is a blockage of an pulmonary artery, artery in the lungs by a substance that has moved from elsewhere in the body through the bloodstream (embolism). Symptoms of a PE may include dyspnea, shortness of breath, chest pain p ...
reported among those given the vaccine, which is much lower than would be expected to occur naturally in a general population of that size.
On 15 March 2021, the German
Paul-Ehrlich Institute (PEI) reported that out of 1.6million vaccinations, seven cases of cerebral vein thrombosis in conjunction with a deficiency of blood platelets had occurred.
According to the PEI, the number of cases of cerebral vein thrombosis after vaccination was statistically significantly higher than the number that would occur in the general population during a similar time period.
These reports prompted the PEI to recommend a temporary suspension of vaccinations until the EMA had completed their review of the cases.
The
World Health Organization
The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...
(WHO) issued a statement on 17 March, regarding the AstraZeneca COVID-19 vaccine safety signals, and still considers the benefits of the vaccine to outweigh its potential risks, further recommending that vaccinations continue. On 18 March, the EMA announced that out of the around 20million people who had received the vaccine, general blood clotting rates were normal, but that it had identified seven cases of
disseminated intravascular coagulation, and eighteen cases of
cerebral venous sinus thrombosis.
A causal link with the vaccine was not proven, but the EMA said it would conduct further analysis and recommended informing people eligible for the vaccine of the fact that the possibility it may cause rare clotting problems had not been disproven.
The EMA confirmed that the vaccine's benefits outweighed the risks.
On 25 March, the EMA released updated product information.
According to the EMA, 100,000 cases of blood clots occur naturally each month in the EU, and the risk of blood clots was not statistically higher in the vaccinated population. The EMA noted that COVID-19 itself causes an increased risk of the development of blood clots, and as such the vaccine would lower the risk of the formation of blood clots even if the 15 cases' causal link were to be confirmed.
Italy resumed vaccinations after the EMA's statement,
with most of the remaining European countries following suit and resuming their AstraZeneca inoculations shortly thereafter.
To reassure the public of the vaccine's safety, the British and French Prime Ministers,
Boris Johnson
Alexander Boris de Pfeffel Johnson (; born 19 June 1964) is a British politician, writer and journalist who served as Prime Minister of the United Kingdom and Leader of the Conservative Party from 2019 to 2022. He previously served as F ...
and
Jean Castex
Jean Castex (; born 25 June 1965) is a French politician who was the country's Prime Minister from 3 July 2020 to 16 May 2022. He was a member of The Republicans (LR) until 2020, when he joined La République En Marche! (LREM). Castex served f ...
, had themselves vaccinated with it in front of the media shortly after the restart of the AstraZeneca vaccination campaigns in the EU.
On 13 April 2021, the EMA issued its direct healthcare professional communication (DHPC) about the vaccine.
The DHPC indicated that a causal relationship between the vaccine and blood clots (
thrombosis
Thrombosis (from Ancient Greek "clotting") is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (thro ...
) in combination with low blood platelets (
thrombocytopenia
Thrombocytopenia is a condition characterized by abnormally low levels of platelets, also known as thrombocytes, in the blood. It is the most common coagulation disorder among intensive care patients and is seen in a fifth of medical patients an ...
) was plausible and identified it as a very rare side effect of the vaccine.
According to the EMA these very rare adverse events occur in around 1 out of 100,000 vaccinated people.
Further development
Efficacy against variants
A study published in April 2021 by researchers from the COVID-19 Genomics United Kingdom Consortium, the AMPHEUS Project, and the Oxford COVID-19 Vaccine Trial Group indicated the Oxford–AstraZeneca vaccine showed somewhat reduced efficacy against infection with the
Alpha variant
The Alpha variant (B.1.1.7) was a SARS-CoV-2 variant of concern. It was estimated to be 40–80% more transmissible than the wild-type SARS-CoV-2 (with most estimates occupying the middle to higher end of this range). It was first detecte ...
(lineage B.1.1.7), with 70.4% efficacy in absolute terms against Alpha versus 81.5% against other variants. Despite this, the researchers concluded that the vaccine remained effective at preventing symptomatic infection from this variant and that vaccinated individuals infected symptomatically typically had shorter duration of symptoms and less
viral load
Viral load, also known as viral burden, is a numerical expression of the quantity of virus in a given volume of fluid, including biological and environmental specimens. It is not to be confused with viral titre or viral titer, which depends on the ...
, thereby reducing the risk of transmission.
Following the identification of
notable variants of concern, concern arose that the
E484K
There are many variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19). Some are believed, or have been stated, to be of particular importance due to their potenti ...
mutation, present in the
Beta
Beta (, ; uppercase , lowercase , or cursive ; grc, βῆτα, bē̂ta or ell, βήτα, víta) is the second letter of the Greek alphabet. In the system of Greek numerals, it has a value of 2. In Modern Greek, it represents the voiced labiod ...
and
Gamma
Gamma (uppercase , lowercase ; ''gámma'') is the third letter of the Greek alphabet. In the system of Greek numerals it has a value of 3. In Ancient Greek, the letter gamma represented a voiced velar stop . In Modern Greek, this letter re ...
variants (lineages B.1.351 and P.1), could evade the protection given by the vaccine.
In February 2021, the collaboration was working to adapt the vaccine to target these variants, with the expectation that a modified vaccine would be available "in a few months" as a "booster" given to people who had already completed the two-dose series of the original vaccine.
In June 2021, AstraZeneca published a press release confirming undergoing Phase II/III trials of an AZD2816 COVID-19 variant vaccine candidate. The new vaccine would be based on the current ''Vaxzevria'' adenoviral vector platform but modified with spike proteins based on the Beta (B.1.351 lineage) variant.
Phase II/III trials saw 2849 volunteers participating from UK, South Africa, Brazil and Poland with parallel dosing of both the current Oxford-AstraZeneca vaccine and the variant vaccine candidate.
By September 2021, AZD2816 vaccine candidate is still undergoing Phase II/III trials with intent to switch to this vaccine if approved by government regulators. Particularly the government of Thailand, with delivery of additional 60 million doses of AstraZeneca COVID-19 Vaccine agreed for 2022.
Heterologous prime-boost vaccination
In December 2020, a clinical trial was registered to examine a
heterologous
The term heterologous has several meanings in biology.
Gene expression
In cell biology and protein biochemistry, heterologous expression means that a protein is experimentally put into a cell that does not normally make (i.e., express) that ...
prime-boost vaccination course consisting of one dose of the Oxford–AstraZeneca vaccine followed by
Sputnik Light
Sputnik Light (russian: Спутник Лайт, Sputnik Layt or Lajt) is a single dose COVID-19 vaccine developed by the Gamaleya Research Institute of Epidemiology and Microbiology. It consists of the first dose of the Sputnik V vaccine, w ...
based on the Ad26 vector 29 days later.
After suspensions due to rare cases of blood clots in March 2021, Canada and several European countries recommended receiving a different vaccine for the second dose. Despite the lack of clinical data on the efficacy and safety of such heterologous combinations, some experts believe that doing so may boost immunity, and several studies have begun to examine this effect.
In June 2021, preliminary results from a study of 463 participants showed that a heterologous prime-boost vaccination course consisting of one dose of the Oxford–AstraZeneca vaccine followed by one dose of the
Pfizer–BioNTech vaccine produced the strongest
T cell activity and an antibody level almost as high as two doses of the Pfizer-BioNTech vaccine. The reversal of the order resulted in T cell activity at half the potency and one-seventh the antibody levels, the latter still five times higher than two doses of Oxford–AstraZeneca. The lowest T cell activity was observed in homologous courses, when both doses were of the same vaccine.
In July 2021, a study of 216 participants found that a heterologous prime-boost vaccination course consisting of one dose of the Oxford–AstraZeneca vaccine followed by one dose of the
Moderna
Moderna, Inc. ( ) is an American pharmaceutical and biotechnology company based in Cambridge, Massachusetts that focuses on RNA therapeutics, primarily mRNA vaccines. These vaccines use a copy of a molecule called messenger RNA (mRNA) to pro ...
vaccine produced a similar level of
neutralizing antibodies
A neutralizing antibody (NAb) is an antibody that defends a cell from a pathogen or infectious particle by neutralizing any effect it has biologically. Neutralization renders the particle no longer infectious or pathogenic.
Neutralizing antibod ...
and
T cell
A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell r ...
responses with increased
spike
Spike, spikes, or spiking may refer to:
Arts, entertainment, and media
Books
* ''The Spike'' (novel), a novel by Arnaud de Borchgrave
* ''The Spike'' (book), a nonfiction book by Damien Broderick
* ''The Spike'', a starship in Peter F. Hamilto ...
-specific
cytotoxic T cell
A cytotoxic T cell (also known as TC, cytotoxic T lymphocyte, CTL, T-killer cell, cytolytic T cell, CD8+ T-cell or killer T cell) is a T lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected by intracellular pa ...
s compared to a homologous course consisting of two doses of the Moderna vaccine.
Society and culture
The Oxford University and AstraZeneca collaboration was seen as having the potential as being a low-cost vaccine with no onerous storage requirements.
A series of events including a deliberate undermining of the AstraZeneca vaccine for geopolitical purposes by both the EU and EU member states including miscommunication, reports of supply difficulties (responsibility of which were due to the EU mis-handling vaccine procurement) misleading reports of inefficacy and adverse effects as well as the high-profile
European Commission–AstraZeneca COVID-19 vaccine dispute, have been a
public relations
Public relations (PR) is the practice of managing and disseminating information from an individual or an organization (such as a business, government agency, or a nonprofit organization) to the public in order to influence their perception. P ...
disaster for both Brussels and member states,
and in the opinion of one academic has led to increased
vaccine hesitancy
Vaccine hesitancy is a delay in acceptance, or refusal, of vaccines despite the availability of vaccine services and supporting evidence. The term covers refusals to vaccinate, delaying vaccines, accepting vaccines but remaining uncertain abou ...
.
The vaccine is a key component of the WHO backed
COVAX
COVID-19 Vaccines Global Access, abbreviated as COVAX, is a worldwide initiative aimed at equitable access to COVID-19 vaccines directed by the GAVI vaccine alliance, the Coalition for Epidemic Preparedness Innovations (CEPI), and the World Hea ...
(COVID-19 Vaccines Global Access) program,
with the WHO, the EMA, and the MHRA continuing to state that the benefits of the vaccine outweigh any possible side effects.
About 69million doses of the Oxford–AstraZeneca COVID-19 vaccine were administered in the EU/EEA from authorization to 26 June 2022.
[ Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.]
Economics
Agreements for access to vaccines began being signed in May 2020, with the UK having priority for the first 100million doses if trials proved successful, with the final agreement being signed at the end of August.
On 21 May 2020, AstraZeneca agreed to provide 300million doses to the US for , implying a cost of per dose.
An AstraZeneca spokesman said the funding also covers development and clinical testing. It also reached a technology transfer agreement with the Mexican and Argentinean governments and agreed to produce at least 400million doses to be distributed throughout Latin America. The active ingredients would be produced in Argentina and sent to Mexico to be completed for distribution. In June 2020,
Emergent BioSolutions
Emergent BioSolutions Inc. is an American multinational specialty biopharmaceutical company headquartered in Gaithersburg, Maryland. It develops vaccines and antibody therapeutics for infectious diseases and opioid overdoses, and it provides m ...
signed a deal to manufacture doses of the AstraZeneca vaccine specifically for the US market. The deal was part of the Trump administration's
Operation Warp Speed
Operation Warp Speed (OWS) was a public–private partnership initiated by the United States government to facilitate and accelerate the development, manufacturing, and distribution of COVID-19 vaccines, therapeutics, and diagnostics. The firs ...
initiative to develop and rapidly scale production of targeted vaccines before the end of 2020.
Catalent
Catalent, Inc. (Catalent Pharma Solutions) is a multinational corporation headquartered in Somerset, New Jersey. It is a global provider of delivery technologies, development, drug manufacturing, biologics, gene therapies and consumer health p ...
would be responsible for the finishing and packaging process.
On 4 June 2020, the WHO's
COVAX
COVID-19 Vaccines Global Access, abbreviated as COVAX, is a worldwide initiative aimed at equitable access to COVID-19 vaccines directed by the GAVI vaccine alliance, the Coalition for Epidemic Preparedness Innovations (CEPI), and the World Hea ...
(COVID-19 Vaccines Global Access) facility made initial purchases of 300million doses from the company for low- to middle-income countries.
Also, AstraZeneca and
Serum Institute of India
Serum Institute of India (SII) is an Indian biotechnology and biopharmaceuticals company, based in Pune. It is the world's largest manufacturer of vaccines. It was founded by Cyrus Poonawalla in 1966 and is a part of Cyrus Poonawalla Group.
...
reached a licensing agreement to independently supply 1billion doses of the Oxford University vaccine to middle- and low-income countries, including India. Later in September, funded by a grant from the
Bill and Melinda Gates Foundation
The Bill & Melinda Gates Foundation (BMGF), a merging of the William H. Gates Foundation and the Gates Learning Foundation, is an American private foundation founded by Bill Gates and Melinda French Gates. Based in Seattle, Washington, it was ...
, the COVAX program secured an additional 100 million doses at US$3 per dose.
On 27 August 2020, AstraZeneca concluded an agreement with the EU, to supply up to 400million doses to all EU and select European Economic Area (EEA) member states.
The European Commission took over negotiations started by the Inclusive Vaccines Alliance, a group made up of France, Germany, Italy, and the Netherlands, in June 2020.
On 5 November 2020, a tripartite agreement was signed between the government of
Bangladesh
Bangladesh (}, ), officially the People's Republic of Bangladesh, is a country in South Asia. It is the eighth-most populous country in the world, with a population exceeding 165 million people in an area of . Bangladesh is among the mos ...
, the Serum Institute of India, and
Beximco Pharma
Beximco Pharmaceuticals Ltd also known as Beximco Pharma, is a pharmaceutical company in Bangladesh. It is part of the Beximco Group of Companies.
Corporate history
Beximco Pharma was founded in 1976 and started operations in 1980, manufacturing ...
of Bangladesh. Under the agreement Bangladesh ordered 30million doses of Oxford–AstraZeneca vaccine from Serum through Beximco for $4 per shot.
On the other hand, Indian government has given 3.2 million doses to Bangladesh as a gift which were also produced by Serum. But Serum supplied only 7 million doses from the tripartite agreement in the first two months of the year.
Bangladesh was supposed to receive 5 million doses per month but not received shipments in March and April.
As a result, rollout of vaccine has been disrupted by supply shortfalls.
The situation became complicated when the second dose of 1.3 million citizens is uncertain as India halts exports.
Not getting the second dose at the right time is likely to reduce the effectiveness of the vaccination program. In addition, several citizens of Bangladesh have expressed doubts about its effectiveness and safety.
Bangladesh is looking for alternative vaccine sources because India isn't supplying the vaccine according to the timeline of the deal.
Thailand's agreement in November 2020 for 26million doses of vaccine
would cover 13million people, approximately 20% of the population, with the first lot expected to be delivered at the end of May. The
public health minister indicated the price paid was $5 per dose;
AstraZeneca (Thailand) explained in January 2021 after a controversy that the price each country paid depended on
production cost
Cost of goods sold (COGS) is the carrying value of goods sold during a particular period.
Costs are associated with particular goods using one of the several formulas, including specific identification, first-in first-out (FIFO), or average cost ...
and differences in
supply chain
In commerce, a supply chain is a network of facilities that procure raw materials, transform them into intermediate goods and then final products to customers through a distribution system. It refers to the network of organizations, people, acti ...
, including manufacturing capacity, labour and raw material costs. In January 2021, the Thai cabinet approved further talks on ordering another 35million doses, and the Thai FDA approved the vaccine for emergency use for 1year. Siam Bioscience, a company owned by
Vajiralongkorn
Vajiralongkorn ( th, วชิราลงกรณ; , ; born 28 July 1952) is the King of Thailand. He is the only son of King Bhumibol Adulyadej and Queen Sirikit. In 1972, at the age of 20, he was made crown prince by his father. After his ...
, will receive technological transfer and has the capacity to manufacture up to 200million doses a year for export to
ASEAN
ASEAN ( , ), officially the Association of Southeast Asian Nations, is a political and economic union of 10 member states in Southeast Asia, which promotes intergovernmental cooperation and facilitates economic, political, security, militar ...
.
Also in November, the
Philippines
The Philippines (; fil, Pilipinas, links=no), officially the Republic of the Philippines ( fil, Republika ng Pilipinas, links=no),
* bik, Republika kan Filipinas
* ceb, Republika sa Pilipinas
* cbk, República de Filipinas
* hil, Republ ...
agreed to buy 2.6million doses,
reportedly worth around million (approximately per dose). In December 2020, South Korea signed a contract with AstraZeneca to secure 20million doses of its vaccine, reportedly equivalent in worth to those signed by Thailand and the Philippines,
with the first shipment expected as early as January 2021. , the vaccine remains under review by the
South Korea Disease Control and Prevention Agency. 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.
On 7 January 2021, the South African government announced that they had secured an initial 1million doses from the Serum Institute of India, to be followed by another 500,000 doses in February,
however the South African government subsequently cancelled the use of the vaccine, selling its supply to other African countries, and switched its vaccination program to use the
Janssen COVID-19 vaccine
The Janssen COVID19 vaccine, sold under the brand name Jcovden, is a COVID19 vaccine that was developed by Janssen Vaccines in Leiden, Netherlands, and its Belgian parent company Janssen Pharmaceuticals, a subsidiary of American company Joh ...
.
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
Novasep, based in Lyon (France), is a group of companies involved in pharmaceutical and biopharmaceutical technologies.
History
The company emerged as a start-up founded by Roger-Marc Nicoud , producing pharmaceuticals, biopharmaceuticals, and p ...
in Belgium. Only 31million of the previously predicted 80million doses would be delivered to the EU by March 2021.
In an interview with Italian newspaper ''
La Repubblica
''la Repubblica'' (; the Republic) is an Italian daily general-interest newspaper. It was founded in 1976 in Rome by Gruppo Editoriale L'Espresso (now known as GEDI Gruppo Editoriale) and led by Eugenio Scalfari, Carlo Caracciolo and Arnoldo ...
'', AstraZeneca's CEO
Pascal Soriot
Sir Pascal Claude Roland Soriot (born 23 May 1959) is a French-born Australian businessman and chief executive officer (CEO) of the British-Swedish multinational pharmaceutical and biotechnology company AstraZeneca.
Early life
Pascal Soriot was ...
said the delivery schedule for the doses in the EU was two months behind schedule. He mentioned low yield from
cell culture
Cell culture or tissue culture is the process by which cells are grown under controlled conditions, generally outside of their natural environment. The term "tissue culture" was coined by American pathologist Montrose Thomas Burrows. This te ...
s at one large-scale European site. Analysis published in ''
The Guardian
''The Guardian'' is a British daily newspaper. It was founded in 1821 as ''The Manchester Guardian'', and changed its name in 1959. Along with its sister papers ''The Observer'' and ''The Guardian Weekly'', ''The Guardian'' is part of the Gu ...
'' also identified an apparently low yield from
bioreactors
A bioreactor refers to any manufactured device or system that supports a biologically active environment. In one case, a bioreactor is a vessel in which a chemical reaction, chemical process is carried out which involves organisms or biochemistry, ...
in the Belgium plant and noted the difficulties in setting up this form of process, with variable yields often occurring.
As a result, the EU imposed export controls on vaccine doses;
controversy erupted as to whether doses were being diverted to the UK and whether deliveries to Northern Ireland would be disrupted.
On 24 February 2021, a shipment of the vaccine to
Accra
Accra (; tw, Nkran; dag, Ankara; gaa, Ga or ''Gaga'') is the capital and largest city of Ghana, located on the southern coast at the Gulf of Guinea, which is part of the Atlantic Ocean. As of 2021 census, the Accra Metropolitan District, , ...
,
Ghana
Ghana (; tw, Gaana, ee, Gana), officially the Republic of Ghana, is a country in West Africa. It abuts the Gulf of Guinea and the Atlantic Ocean to the south, sharing borders with Ivory Coast in the west, Burkina Faso in the north, and To ...
, via COVAX made it the first country in
Africa
Africa is the world's second-largest and second-most populous continent, after Asia in both cases. At about 30.3 million km2 (11.7 million square miles) including adjacent islands, it covers 6% of Earth's total surface area ...
to receive vaccines via the initiative.
In early 2021, the
Bureau for Investigative Journalism
The Bureau of Investigative Journalism (typically abbreviated to TBIJ or "the Bureau") is a nonprofit news organisation based in London. It was founded in 2010 to pursue "public interest" investigations. [South Africa
South Africa, officially the Republic of South Africa (RSA), is the southernmost country in Africa. It is bounded to the south by of coastline that stretch along the South Atlantic and Indian Oceans; to the north by the neighbouring countri ...]
had paid double the rate for the European Commission, while
Uganda
}), is a landlocked country in East Africa
East Africa, Eastern Africa, or East of Africa, is the eastern subregion of the African continent. In the United Nations Statistics Division scheme of geographic regions, 10-11-(16*) territor ...
paid triple.
["Unlike AstraZeneca, the Serum Institute has not promised to keep to cost price, and is charging India $3 per dose, South Africa and Brazil $5, and Uganda $7, where the EU only paid AstraZeneca $2."]
Brand names
The vaccine is marketed under the brand name Covishield by the
Serum Institute of India
Serum Institute of India (SII) is an Indian biotechnology and biopharmaceuticals company, based in Pune. It is the world's largest manufacturer of vaccines. It was founded by Cyrus Poonawalla in 1966 and is a part of Cyrus Poonawalla Group.
...
.
The name of the vaccine was changed to Vaxzevria in the European Union on 25 March 2021.
Vaxzevria, AstraZeneca COVID‐19 Vaccine, and COVID-19 Vaccine AstraZeneca are manufactured by AstraZeneca.
Research
, the AZD1222 development team is working on adapting the vaccine to be more effective in relation to newer
SARS-CoV-2 variants
There are many variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19). Some are believed, or have been stated, to be of particular importance due to their potenti ...
; redesigning the vaccine being the relatively quick process of switching the genetic sequence of the spike protein.
Manufacturing set-up and a small scale trial are also required before the adapted vaccine might be available in autumn.
References
Further reading
*
External links
*
*
*
*
*
*
"An oral history of Oxford/AstraZeneca: 'Making a vaccine in a year is like landing a human on the moon'" ''The Guardian''
{{DEFAULTSORT:Oxford-Astrazeneca Covid-19 Vaccine
Adenoviridae
AstraZeneca brands
Clinical trials
British COVID-19 vaccines
Products introduced in 2020
Vaccine controversies
Viral vector vaccines
Withdrawn drugs