The vaccine arose from a collaboration between Oxford University's
Jenner Institute and
Vaccitech, a private company spun off from the university, with financing from
Oxford Sciences Innovation,
Google Ventures, and
Sequoia Capital, among others. The first batch of the COVID-19 vaccine produced for clinical testing was developed by Oxford University's Jenner Institute and the
Oxford Vaccine Group in collaboration with Italian manufacturer Advent Srl located in
Pomezia. The team is led by
Sarah Gilbert,
Adrian Hill,
Andrew Pollard,
Teresa Lambe, Sandy Douglas and
Catherine Green. Originally, Oxford intended to donate the rights to manufacture and market the vaccine to any drugmaker who wanted to do so, but after the
Gates Foundation urged Oxford to find a large company partner to get its COVID-19 vaccine to market, the university withdrew this offer in May 2020. The UK government then encouraged Oxford to work with AstraZeneca, a company based in Europe, instead of
Merck & Co., a US-based company (
The Guardian reported the initial partner was the German-based
Merck Group 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. 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 (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 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 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 surrounding a patient illness that triggered a clinical hold, according to the
US Department of Health and Human Services (HHS) Secretary
Alex Azar. 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 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 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, 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. However, the results did not show any protection against asymptomatic COVID-19 following only one dose. 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 (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 reported a final 74% efficacy rate against symptomatic disease in the trial conducted in the United States, Chile and Peru.
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. 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 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. 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 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 (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. In February 2021, the government and regulatory authorities in Australia (16 February 2021) On 19 November 2021, the vaccine was approved for use in Canada. The
BBC 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 (lineage B.1.351), particularly in preventing serious illness and death. 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 Beta variant. In total, four cases of blood clots have been identified in the same batch of 1million doses. several other countries, including Denmark, Bulgaria, Ireland, Italy, 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. In March 2021, the
Norwegian government temporarily suspended the vaccine's use, awaiting more information regarding potential adverse effects. Then, in April, the
Norwegian Institute of Public Health 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. In May, the expert committee also recommended suspending the use of both vaccines. Finally, in May —two months after the initial suspension— the
Prime Minister of Norway 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. 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". 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 "[weighed] against 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." In October 2022, the conditional marketing authorisation was converted to a standard one. AstraZeneca withdrew its marketing authorization for the vaccine from the European Union in March 2024. 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 2021, 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 was a recommendation which did not affect the formal approval of the vaccine by
Health Canada for all adults over 18; it stated on 14 April 2021 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 2021, citing the current state of supplies for mRNA-based vaccines and new data, NACI issued a recommendation that the vaccine could be offered to patients as young as 30 years old if benefits outweighed the risks, and the patient did "not wish to wait for an mRNA vaccine". Beginning 11 May 2021, 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 2021, 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 March 2021, 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 In 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 in late April 2021. The AstraZeneca vaccines was distributed in designated vaccination centres, with the public being allowed to 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. On 10 May 2024,
Health Minister Dzulkefly Ahmad announced that the Malaysian Government would continue to offer care to individuals suffering from adverse effects of COVID-19 vaccines including the AstraZeneca vaccine. He also confirmed that the Malaysian Government had data on adverse effects caused by COVID-19 vaccines and methods for treating the side effects. On 13 May, Deputy Health Minister
Lukanisman Awang Sauni confirmed that the Malaysian Government would release a report on the AstraZeneca vaccine's adverse effects later in the week.
Safety review In March 2021, the
European Medicines Agency (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 events in vaccinated people was no higher than that seen in the general population. 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 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. 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. The
World Health Organization (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. 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 and
Jean Castex, had themselves vaccinated with it in front of the media shortly after the restart of the AstraZeneca vaccination campaigns in the EU. In 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) in combination with low blood platelets (
thrombocytopenia) was plausible and identified it as a very rare side effect of the vaccine. 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, thereby reducing the risk of transmission. Following the identification of
notable variants of concern, concern arose that the
E484K mutation, present in the
Beta and
Gamma 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.
Heterologous prime-boost vaccination In December 2020, a clinical trial was registered to examine a
heterologous prime-boost vaccination course consisting of one dose of the Oxford–AstraZeneca vaccine followed by
Sputnik Light 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 vaccine produced a similar level of
neutralizing antibodies and
T cell responses with increased
spike-specific
cytotoxic T cells compared to a homologous course consisting of two doses of the Moderna vaccine. ==Society and culture==