AZD1222 (ChAdOx1), Oxford–AstraZeneca COVID-19 vaccine, COVISHIELD

AZD1222 (ChAdOx1)

ChAdOx1 nCoV- 19 Corona Virus Vaccine (Recombinant) COVISHIELD

• DNA (recombinant simian adenovirus Ox1 ΔE1E3 vector human cytomegalovirus promoter plus human tissue plasminogen activator signal peptide fusion protein with severe acute respiratory syndrome coronavirus 2 isolate Wuhan-​Hu-​1 spike glycoprotein codon optimized-​specifying)

The University of Oxford, AstraZeneca vaccine is a vaccine that aims to protect against COVID-19.

Manufacturer/developer: AstraZeneca, University of OxfordResearch name: AZD1222 (ChAdOx1)Vaccine type: Non-Replicating Viral VectorAdministration method: Intramuscular injection

Biological Components:

Covishield is a viral vector vaccine. It uses a weakened, non-replicating strain of Chimpanzee cold virus (adenovirus) to carry genetic material of the spike protein of SARS-CoV-2 into human cells

Vial of the Oxford–AstraZeneca vaccine manufactured by the Serum Institute of India (marketed as Covishield in India and in a few other countries).^[5]

COVISHIELD INGREDIENTS

L-Histidine Ethanol

L-Histidine Hydrochloride Monohydrate,Magnesium Chloride

Hexahydrate Polysorbate 80*, Sucrose, Sodium Chloride

Disodium Edetate Dihydrate (EDTA) ,   Water for injection

Polysorbate 80 which is an ingredient of Covishield is known to cause anaphylactic reactions in patients as can be read here whereas Covaxin has no such component.

NAME	DOSAGE	STRENGTH	ROUTE	LABELLER	MARKETING START	MARKETING END
Astrazeneca Covid-19 Vaccine	Injection, suspension	50000000000 {VP}/0.5mL	Intramuscular	AstraZeneca Pharmaceuticals LP	2020-12-22	Not applicable

Storage Conditions:  can be stored at 2 to 8 degrees Celsius making them convenient to store and transport.

Mechanism of Immunization: Covishield – This vaccine produces antibodies against only a specific region of the virus. It contains a portion of the DNA that codes for the spike protein (S-protein). Once inside the cells, the DNA part first needs to enter the nucleus to create its mirror image (complementary RNA). Then this RNA comes out in the cytoplasm as a messenger and starts making S-protein through a machine available for this purpose called ribosome. Since it is S-protein that provokes immunity it may not be as close to natural immunity as created by Covaxin. If there are any long-term side effects of the DNA material remaining inside the nucleus (e.g. integration in human DNA) is not yet known. So far, DNA vaccines were only being tried out for treating cancer patients and never used for preventing infections in normal subjects.

Clinical Development: Covishield has been developed by AstraZeneca with Oxford university in the UK and is being manufactured by the Serum Institute India (SII) in Pune. Covishield has completed phase 3 trials in S. Africa, Brazil and UK. 90% of the subjects in these studies were under the age of 55 making the efficacy and safety data applicable to this age group. The company has presented bridging study results in Indian population to the regulatory authorities based on which the approval was granted by DCGI. This data is not yet available in the public domain

Dosage Regimen: Covishield has been recommended to be taken in 2 doses. Observation of data from the UK shows improved protection with a gap of 12 weeks between 2 doses; though currently the expert committee set up by the Drug Controller General of India (DCGI) has recommended a gap of 4 weeks. Covaxin has been recommended to be taken in 2 doses 4 weeks apart.

Efficacy: Covishield has an average efficacy of 70% when 2 doses are administered 4 weeks apart. This data is from a meta-analysis (pooled analysis of multiple studies) of 4 Covishield trials in 11,636 patients out of which 3 trials were single blind and one double blind in 3 different countries. The efficacy of Covishield was published in The Lancet (link to the article). Observation of data has shown that the efficacy improves as the gap between the 2 doses is increased reaching a reported efficacy of 82.4% with a 12-week gap. Since, the phase-3 trials were conducted with a 4-week interval, it has become the standard.

Protection against Mutations: Preliminary research shows both vaccines are effective against the variant of the novel coronavirus first detected in the UK but there is no data on their efficacy against the mutants found in South Africa and Brazil. Data against these 2 variants is yet to be generated for both these vaccines.

. Consent: Covishield does not require any consent form as it has completed the phase-3 clinical trials

Who should not take Covishield?

Serum Institute of India’s factsheet said one should not get the Covishield vaccine if the person had a severe allergic reaction after a previous dose of this vaccine. Like Bharat Biotech, the SII factsheet also says that if a person is pregnant or plans to become pregnant or is breastfeeding she should tell the healthcare provider before taking the jab. People who have taken another anti-Covid vaccine should not take Covishield.

The ingredients of the Covishield vaccine are “L-Histidine, L-Histidine hydrochloride monohydrate, Magnesium chloride hexahydrate, Polysorbate 80, Ethanol, Sucrose, Sodium chloride, Disodium edetate dihydrate (EDTA), Water for injection,” it pointed out.

Side-effects of Covishield

Some of the very common side effects of the vaccines are tenderness, pain, warmth, redness, itching, swelling or bruising where the injection is given, generally feeling unwell, chills or feeling feverish, headache or joint aches.

Covishield is made by Serum Institute of India (SII) and Covaxin is manufactured by Bharat Biotech.

Over 50 lakh people have registered themselves on the Co-WIN portal since the window opened on Monday morning, the Centre said. Nearly 5 lakh beneficiaries above 60 or those aged 45-60 with comorbidities have received the first jab of Covid-19 vaccine till Tuesday evening.

Meanwhile, the govt has permitted all private hospitals to give Covid-19 vaccine if they adhere to the laid down norms and also asked the states and union territories to utilise the optimum capacity of private medical facilities empanelled under three categories. The states and Union Territories were also urged not to store, reserve, conserve or create a buffer stock of the COVID-19 vaccines, the Union Health Ministry said in a statement.

Sources:  https://www.bbc.com/news/world-asia-india-55748124

The Oxford–AstraZeneca COVID-19 vaccine, codenamed AZD1222,^[7] is a COVID-19 vaccine developed by Oxford University and AstraZeneca given by intramuscular injection, using as a vector the modified chimpanzee adenovirus ChAdOx1.^{[18][19][20][21]} One dosing regimen showed 90% efficacy when a half-dose was followed by a full-dose after at least one month, based on mixed trials with no participants over 55 years old.^[6] Another dosing regimen showed 62% efficacy when given as two full doses separated by at least one month.^[6]

The research is being done by the Oxford University’s Jenner Institute and Oxford Vaccine Group with the collaboration of the Italian manufacturer Advent Srl located in Pomezia, which produced the first batch of the COVID-19 vaccine for clinical testing.^[22] The team is led by Sarah Gilbert, Adrian Hill, Andrew Pollard, Teresa Lambe, Sandy Douglas and Catherine Green.^[23][22]

On 30 December 2020, the vaccine was first approved for use^[11][24] in the UK’s vaccination programme,^[25] and the first vaccination outside of a trial was administered on 4 January 2021.^[26] The vaccine has since been approved by several medicine agencies worldwide, such as the European Medicines Agency,^[12][14] and the Australian Therapeutic Goods Administration (TGA),^[9] and has been approved for an Emergency Use Listing (EUL) by the World Health Organization.^[27]

Vaccine platform

The AZD1222 vaccine is a replication-deficient simian adenovirus vector, containing the full‐length codon‐optimised coding sequence of SARS-CoV-2 spike protein along with a tissue plasminogen activator (tPA) leader sequence.^[28][29].

The adenovirus is said replication-deficient because some of its essential genes were deleted and replaced by a gene coding for the spike. Following vaccination, the adenovirus vector enters the cells, releases its genes, those are transported to the cell nucleus, thereafter the cell’s machinery does the transcription in mRNA and the translation in proteins.

The one of interest is the spike protein, an external protein that enables the SARS-type coronavirus to enter cells through the enzymatic domain of ACE2.^[30] Producing it following vaccination will prompt the immune system to attack the coronavirus through antibodies and T-cells if it later infects the body.^[6]

History

2020 development

In February 2020, the Jenner Institute agreed a collaboration with the Italian company Advent Srl for the production of the first batch of a vaccine candidate for clinical trials.^[31]

In March 2020,^[32][33] after the Gates Foundation urged the University of Oxford to find a large company partner to get its COVID-19 vaccine to market, the university backed off from its earlier pledge to donate the rights to any drugmaker.^[34] Also, the UK government encouraged the University of Oxford to work with AstraZeneca instead of Merck & Co., a US based company over fears of vaccine hoarding under the Trump administration.^[35]

In June 2020, the US National Institute of Allergy and Infectious Diseases (NIAID) confirmed that the third phase of testing for potential vaccines developed by Oxford University and AstraZeneca would begin in July 2020.^[36]

Clinical trials

In July 2020, AstraZeneca partnered with IQVIA to speed up US clinical trials.^[37]

On 31 August 2020, AstraZeneca announced that it had begun enrolling adults for a US-funded, 30,000-subject late-stage study.^[38]

On 8 September 2020, AstraZeneca announced a global halt to the vaccine trial while a possible adverse reaction in a participant in the United Kingdom was investigated.^[39][40][41] On 13 September, AstraZeneca and the University of Oxford resumed clinical trials in the United Kingdom after regulators concluded it was safe to do so.^[42] AstraZeneca was criticised for vaccine safety after concerns from experts noting the company’s refusal to provide details about serious neurological illnesses in two participants who received the experimental vaccine in Britain.^[43] While the trial resumed in the UK, Brazil, South Africa, Japan^[44] and India, it remained on pause in the US till 23 October 2020^[45] while the Food and Drug Administration (FDA) investigated a patient illness that triggered the clinical hold, according to the United States Department of Health and Human Services (HHS) Secretary Alex Azar.^[46]

On 15 October 2020, Dr João Pedro R. Feitosa, a 28-year-old doctor from Rio de Janeiro, Brazil, who received a placebo instead of the test vaccine in a clinical trial of AZD1222, died from COVID-19 complications.^[47][48][49] The Brazilian health authority Anvisa announced that the trial would continue in Brazil.^[50]

Results of Phase III trial

On 23 November 2020, Oxford University and AstraZeneca announced interim results from the vaccine’s ongoing Phase III trials.^[6][51] There was some criticism of the methods used in the report, which combined results of 62% and 90% from different groups of test subjects given different dosages to arrive at a 70% figure.^[52][53][54] AstraZeneca said it would carry out a further multi-country trial using the lower dose which had led to a 90% claim.^[55]

The full publication of the interim results from four ongoing Phase III trials on 8 December 2020 clarified these reports.^[56] In the group who received the first dose of active vaccine more than 21 days earlier, there were no hospitalisations or severe disease, unlike those receiving the placebo. Serious adverse events were balanced across the active and control arms in the studies, i.e. the active vaccine did not have safety concerns. A case of transverse myelitis was reported 14 days after booster vaccination as being possibly related to vaccination, with an independent neurological committee considering the most likely diagnosis to be of an idiopathic, short segment, spinal cord demyelination. The other two cases of transverse myelitis, one in the vaccine group and the other in the control group, were considered to be unrelated to vaccination.^[56]

A subsequent analysis, published on 19 February, has shown an efficacy of 76% 22 days after the first dose and increase to 81.3% when the second dose is given 12 weeks or more after the first.^[57]

2021 development

In February 2021, Oxford–AstraZeneca indicated developments to adapt the vaccine to target new variants of the coronavirus,^[58] with expectation of a modified vaccine being available “in a few months” as a “booster jab”.^[59] A key area of concern is whether the E484K mutation could impact the immune response and, possibly, current vaccine effectiveness.^[60] The E484K mutation is present in the South African (B.1.351) and Brazilian (B.1.1.28) variants, with a small number of cases of the mutation also detected in infections by the original SARS-CoV-2 virus and the UK/Kent (B.1.1.7) variant.^[60]

Scottish Study

A study was carried out by universities across Scotland of the effectiveness of first dose of Pfizer–BioNTech and Oxford–AstraZeneca COVID-19 vaccines against hospital admissions in Scotland, based on a national prospective cohort study of 5.4 million people. Between 8 December 2020 to 15 February 2021, 1,137,775 patients were vaccinated in the study, 490,000 of which were with the Oxford–AstraZeneca vaccine. The first dose of the Oxford–AstraZeneca vaccine was associated with a vaccine effect of 94% for COVID-19 related hospitalisation at 28–34 days post-vaccination. Results for both vaccines combined showed a vaccine effect for prevention of COVID-19 related hospitalisation which was comparable when restricting the analysis to those aged ≥80 years (81%). The majority of the patients over the age of 65 were given the Oxford–AstraZeneca vaccine. As of 22 February 2021, the study had not been peer-reviewed.^[61][62]

Approvals

On 27 November 2020, the UK government asked the Medicines and Healthcare products Regulatory Agency to assess the AZD1222 vaccine for temporary supply,^[63] and it was approved for use on 30 December 2020, as their second vaccine to enter the national rollout.^[64]

On 4 January 2021, Brian Pinker, 82, became the first person to receive the Oxford–AstraZeneca COVID-19 vaccine outside of clinical trials.^[26]

The European Medicines Agency (EMA) received an application for a conditional marketing authorisation (CMA) for the vaccine on 12 January 2021. A press release stated that a recommendation on this could be issued by the agency by 29 January, with the European Commission then making a decision on the CMA within days.^[3] The Hungarian regulator unilaterally approved the vaccine instead of waiting for EMA approval.^[65]

On 29 January 2021, the EMA recommended granting a conditional marketing authorisation for AZD1222 for people 18 years of age and older,^[12][13] and the recommendation was accepted by the European Commission the same day.^[14][66]

On 30 January 2021, the Vietnamese Ministry of Health approved the AstraZeneca vaccine for domestic inoculation, the first to be approved in Vietnam.^[67]

The vaccine has also been approved by Argentina,^[68] Bangladesh,^[69] Brazil,^[70] the Dominican Republic,^[71] El Salvador,^[72] India,^[73][74] Malaysia,^[75] Mexico,^[76] Nepal,^[77] Pakistan,^[78] the Philippines,^[79] Sri Lanka,^[80] and Taiwan^[81] regulatory authorities for emergency usage in their respective countries.

On 7 February 2021, the vaccine roll out in South Africa was suspended. Researchers from the University of the Witwatersrand said in a prior-to-peer analysis that the AstraZeneca vaccine provided minimal protection against mild or moderate disease infection among young people.^[82][83] The BBC reported on 8 February 2021 that Katherine O’Brien, director of immunisation at the World Health Organization, indicated she felt it was “really plausible” the AstraZeneca vaccine could have a “meaningful impact” on the South African variant particularly in preventing serious illness and death.^[84] The same report also indicated the Deputy Chief Medical Officer for England Jonathan Van-Tam said the (Witwatersrand) study did not change his opinion that the AstraZeneca vaccine was “rather likely” to have an effect on severe disease from the South African variant.^[84]

On 10 February 2021, South Korea granted its first approval of a COVID-19 vaccine to AstraZeneca, allowing the two-shot regimen to be administered to all adults, including the elderly. The approval came with a warning, however, that consideration is needed when administering the vaccine to individuals over 65 years of age due to limited data from that demographic in clinical trials.^[85][86]

On 10 February 2021, the World Health Organization (WHO) issued interim guidance and recommended the AstraZeneca vaccine for all adults, its Strategic Advisory Group of Experts also having considered use where variants were present and concluded there was no need not to recommend it.^[87]

On 16 February 2021, the Australian Therapeutic Goods Administration (TGA) granted provisional approval for COVID-19 Vaccine AstraZeneca.^[9][1]

On 26 February 2021, the vaccine was authorized with terms and conditions by Health Canada.^[88]

Production and supply

The vaccine is stable at refrigerator temperatures and costs around US$3 to US$4 per dose.^[89] On 17 December, a tweet by the Belgian Budget State Secretary revealed the European Union (EU) would pay €1.78 (US$2.16) per dose.^[90]

According to AstraZeneca’s vice-president for operations and IT, Pam Cheng, the company would have around 200 million doses ready worldwide by the end of 2020, and capacity to produce 100 million to 200 million doses per month once production is ramped up.^[52]

In June 2020, further to making 100 million doses available to the UK’s NHS for their vaccination programme,^[91] AstraZeneca and Emergent BioSolutions signed a US$87 million deal to manufacture doses of the vaccine specifically for the US market. The deal was part of the Trump administration’s Operation Warp Speed initiative to develop and rapidly scale production of targeted vaccines before the end of 2020.^[92] Catalent will be responsible for the finishing and packaging process.^[93] The majority of manufacturing work will be done in the UK.^{[citation needed]}

On 4 June 2020, the World Health Organization‘s (WHO) COVAX facility made initial purchases of 300 million doses from the company for low- to middle-income countries.^[94] Also, AstraZeneca and Serum Institute of India reached a licensing agreement to supply 1 billion doses of the Oxford University vaccine to middle- and low-income countries, including India.^[95][96]

On 29 September 2020, a grant from the Bill and Melinda Gates Foundation allowed COVAX to secure an additional 100 million COVID-19 vaccine doses either from AstraZeneca or from Novavax at US$3 per dose.^[97]

On 13 June 2020, AstraZeneca signed a contract with the Inclusive Vaccines Alliance, a group formed by France, Germany, Italy, and the Netherlands, to supply up to 400 million doses to all European Union member states.^{[98][99][100]} However, the European Commission intervened to stop the deal being formalised. It took over negotiations on behalf of the whole EU, signing a deal at the end of August.^[101]

In August 2020, AstraZeneca agreed to provide 300 million doses to the USA for US$1.2 billion, implying a cost of US$4 per dose. An AstraZeneca spokesman said the funding also covers development and clinical testing.^[102] It also reached technology transfer agreement with Mexican and Argentinean governments and agreed to produce at least 400 million doses to be distributed throughout Latin America. The active ingredients would be produced in Argentina and sent to Mexico to be completed for distribution.^[103]

In September 2020, AstraZeneca agreed to provide 20 million doses to Canada.^[104][105]

In October 2020, Switzerland signed an agreement with AstraZeneca to pre-order up to 5.3 million doses.^[106][107]

On 5 November 2020, a tripartite agreement was signed between the government of Bangladesh, Serum Institute of India and Beximco Pharma of Bangladesh. Under the agreement Bangladesh ordered 30 million doses of Oxford–AstraZeneca vaccine from Serum through Beximco for $4 per shot.^[108]

In November 2020, Thailand ordered 26 million doses of vaccine from AstraZeneca.^[109] It would cover 13 million people,^[110] approximately 20% of the population, with the first lot expected to be delivered at the end of May.^{[111][112][113]} The public health minister indicated the price paid was $5 per dose;^[114] AstraZeneca (Thailand) explained in January 2021 after a controversy that the price each country paid depended on production cost and differences in supply chain, including manufacturing capacity, labour and raw material costs.^[115] In January 2021, the Thai cabinet approved further talks on ordering another 35 million doses^[116] and the Thai FDA approved the vaccine for emergency use for 1 year.^[117][118] Siam Bioscience, a company owned by Vajiralongkorn, will received technological transfer,^[119] and has the capacity to manufacture up to 200 million doses a year for export to ASEAN.^[120]

Also in November, the Philippines agreed to buy 2.6 million doses,^[121] reportedly worth around ₱700 million (approximately $5.6/dose).^[122]

In December 2020, South Korea signed a contract with AstraZeneca to secure 20 million doses of its vaccine, reportedly worth equivalently to those signed by Thailand and the Philippines,^[123] with the first shipment expected as early as January 2021. As of January 2021, the vaccine remains under review by the South Korea Disease Control and Prevention Agency.^[124][125] 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.^[126]

On 7 January 2021, the South African government announced that they had secured an initial 1 million doses from the Serum Institute of India, to be followed by another 500,000 doses in February.^[127]

Myanmar signed a contract with Serum Institute of India to secure 30 million doses of its vaccine in December 2020. Myanmar will get doses for 15 million people from February 2021.^[128]

On 22 January 2021, AstraZeneca announced that in the event the European Union approved the COVID-19 Vaccine AstraZeneca, initial supplies would be lower than expected due to production issues at Novasep in Belgium. Only 31 million of the previously predicted 80 million doses would be delivered to the European Union by March 2021.^[129] In an interview with Italian newspaper La Repubblica, AstraZeneca’s CEO Pascal Soriot said the delivery schedule for the doses in the European Union was two months behind schedule. He mentioned low yield from cell cultures in one large-scale European site.^[130] Analysis published in The Guardian also identified an apparently low yield from bioreactors in the Belgium plant and noted the difficulties in setting up this form of process, with variable yields often occurring.^[131] As a result, the European Union imposed export controls on vaccine doses; controversy erupted as to whether doses were being diverted to the UK, and whether or not deliveries to Northern Ireland would be disrupted.^[132]

On 24 February 2021, Ghana became the first country in Africa to receive the Covid-19 vaccine through the COVAX initiative, where the facility sent six hundred thousand doses of AstraZeneca/Oxford jabs to Accra.^[133]

Summary

Background

A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials.

Methods

This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 10¹⁰ viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674.

Findings

Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; p_interaction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation.

Interpretation

ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials.

Funding

UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D’Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland’s NIHR Clinical Research Network, and AstraZeneca.

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External links

Scholia has a profile for AZD1222 (Q95042269).

• “Medical Information site for COVID-19 Vaccine AstraZeneca”. AstraZeneca.
• “Vaccines: contract between European Commission and AstraZeneca now published”. European Commission.
• “How the Oxford-AstraZeneca Covid-19 Vaccine Works”. The New York Times.
• Background document on the AZD1222 vaccine against COVID-19 developed by Oxford University and AstraZeneca. World Health Organization (WHO) (Report).
• Australian Public Assessment Report for ChAdOx1-S (PDF) (Report).

////////AZD1222, ChAdOx1, Oxford–AstraZeneca,  COVID 19 vaccine,  COVISHIELD, CORONA, COVID 19, CORONA VIRUS

#AZD1222, #ChAdOx1, #Oxford–AstraZeneca,  #COVID 19 vaccine,  #COVISHIELD, #CORONA, #COVID 19, #CORONA VIRUS