Oxford University breakthrough on global COVID-19 vaccine

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The University of Oxford, in collaboration with AstraZeneca plc, today announces interim trial data from its Phase III trials that show its candidate vaccine, ChAdOx1 nCoV-2019, is effective at preventing COVID-19 (SARS-CoV-2) and offers a high level of protection.

 

Our vaccine work is progressing quickly. To ensure you have the latest information or to find out more about the trial, please visit the Oxford COVID-19 vaccine web hub or visit the COVID-19 trial website. 

 

• Phase 3 interim analysis including 131 Covid-19 cases indicates that the vaccine is 70.4% effective when combining data from two dosing regimens

 

• In the two different dose regimens vaccine efficacy was 90% in one and 62% in the other

 

• Higher efficacy regimen used a halved first dose and standard second dose

 

• Early indication that vaccine could reduce virus transmission from an observed reduction in asymptomatic infections

 

• There were no hospitalised or severe cases in anyone who received the vaccine

 

• Large safety database from over 24,000 volunteers from clinical trials in the UK, Brazil and South Africa, with follow up since April

 

• Crucially, vaccine can be easily administered in existing healthcare systems, stored at ‘fridge temperature’ (2-8 °C) and distributed using existing logistics

 

• Large scale manufacturing ongoing in over 10 countries to support equitable global access

Professor Andrew Pollard, Director of the Oxford Vaccine Group and Chief Investigator of the Oxford Vaccine Trial, said:

 

‘These findings show that we have an effective vaccine that will save many lives. Excitingly, we’ve found that one of our dosing regimens may be around 90% effective and if this dosing regimen is used, more people could be vaccinated with planned vaccine supply. Today’s announcement is only possible thanks to the many volunteers in our trial, and the hard working and talented team of researchers based around the world.’

 

Professor Sarah Gilbert, Professor of Vaccinology at the University of Oxford, said:

 

‘The announcement today takes us another step closer to the time when we can use vaccines to bring an end to the devastation caused by SARS-CoV-2. We will continue to work to provide the detailed information to regulators. It has been a privilege to be part of this multi-national effort which will reap benefits for the whole world.’ 

 

Following the trial reaching the target for interim analysis, the independent Data and Safety Monitoring Board (DSMB) recommended that the team at Oxford conduct its first analysis on all the cases with data locked on 4 November 2020.

 

These preliminary data indicate that the vaccine is 70.4% effective, with tests on two different dose regimens showing that the vaccine was 90% effective if administered at a half dose and then at a full dose, or 62% effective if administered in two full doses.

 

Additional cases are expected to accrue by the time of the final analysis and future analyses will determine the duration of protection. No serious safety events related to the vaccine have been identified.

 

Oxford will now support AstraZeneca in submitting both the interim Phase III efficacy data and the extensive safety data to all regulators across the world, including in the UK, Europe and Brazil for independent scrutiny and product approval, including for emergency use. Many of these regulators have been reviewing the trial data on a rolling basis during the trial.

 

In parallel, Oxford is submitting the full analysis of the Phase III interim data for independent scientific peer review and publication. The coordination of the programme and execution of the trials in the UK would not have been possible without the support of the National Institute for Health Research and UKRI.

 

These data also suggest that this half dose and full dose regimen could help to prevent transmission of the virus, evidenced by lower rates of asymptomatic infection in the vaccinees, with further information to become available when trial data are next evaluated.

 

The interim Phase III data builds on Oxford’s phase I/II peer-reviewed trial results which have shown that the vaccine induces strong antibody and T cell immune responses across all age groups, including older adults, and has a good safety profile.

 

The clinical trials, enrolling over 24,000 participants from diverse racial and geographical groups in the UK, Brazil and South Africa, will now continue to final analysis. Further trials are being conducted in the United States, Kenya, Japan and India and the trial team expect to have under 60,000 participants by the end of the year. These trials will provide regulators with further information about the efficacy and safety of the Oxford candidate vaccine, including its ability to both protect against and stop the transmission of COVID-19.

 

The Oxford vaccine (ChAdOx1 nCoV-19) is made from a virus, which is a weakened version of a common cold virus (adenovirus), that has been genetically changed so that it is impossible for it to grow in humans. 

 

Adenovirus vaccines have been researched and used extensively for decades and have the significant benefit that they are stable, easily manufactured, transported and stored at domestic fridge temperature (2-8 degrees C). This means they can be easily distributed using existing medical facilities such as doctor’s surgeries and local pharmacies, allowing for the vaccine, if approved, to be deployed very rapidly. 

 

Oxford University’s collaboration with AstraZeneca has been crucial to the successful development of the vaccine and vital for its global manufacturing and distribution across the world. AstraZeneca already has international agreements in place to supply three billion doses of the vaccine, with access being built through more than 30 supply agreements and partner networks.

 

A key element of Oxford’s partnership with AstraZeneca is the joint commitment to provide the vaccine on a not-for-profit basis for the duration of the pandemic across the world, and in perpetuity to low- and middle-income countries. 

Professor Louise Richardson, Vice-Chancellor at the University of Oxford, said:

 

‘This is a great day for the University of Oxford and for universities everywhere. Pushing at the frontiers of knowledge with partners across the globe and putting our extraordinary brainpower in service to society, is what we do best.’

 

Pascal Soriot, Chief Executive Officer, AstraZeneca, said:

 

‘Today marks an important milestone in our fight against the pandemic. This vaccine’s efficacy and safety confirm that it will be highly effective against COVID-19 and will have an immediate impact on this public health emergency. Furthermore, the vaccine’s simple supply chain and our no-profit pledge and commitment to broad, equitable and timely access means it will be affordable and globally available supplying hundreds of millions of doses on approval.’

 

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[mp68terr]

"In parallel, Oxford is submitting the full analysis of the Phase III interim data for independent scientific peer review and publication."

 

"Adenovirus vaccines have been researched and used extensively for decades and have the significant benefit that they are stable, easily manufactured, transported and stored at domestic fridge temperature (2-8 degrees C). This means they can be easily distributed using existing medical facilities such as doctor’s surgeries and local pharmacies, allowing for the vaccine, if approved, to be deployed very rapidly."

 

Two very good points for the 3rd winner.

[Karlston]

AstraZeneca’s COVID-19 vaccine shows success: Here’s how it stacks up to others

AstraZeneca used two dosages: One 62% effective, the other 90%, for 70% average.

Enlarge / Vials in front of the AstraZeneca British biopharmaceutical company logo are seen in this creative photo taken on 18 November 2020.

Getty| NurPhoto

1 with 1 posters participating

AstraZeneca announced in a press release on Monday that its COVID-19 vaccine showed positive results in an interim analysis of clinical trial data.

 

The announcement marks the third vaccine to show strong efficacy in late-stage trials against the pandemic coronavirus, SARS-CoV-2. Though AstraZeneca’s vaccine efficacy numbers are not as impressively high as those for the vaccines before it—mRNA vaccines from Pfizer/BioNTech and Moderna—AstraZeneca's does offer some advantages over those vaccines.

 

In all, the news adds to ballooning optimism that effective vaccines could bring an end to the global crisis in the coming year.

The vaccine and its data

AstraZeneca partnered with researchers at the University of Oxford to develop the viral vector-based vaccine called AZD1222 (also called ChAdOx1 nCoV-19). The vaccine involves having genetic material coding for the notorious SARS-CoV-2 spike protein carried into the body by a relatively benign virus. In this case, the virus is a weakened type of adenovirus—a pathogen that can cause common colds and other mild infections in humans and some animals. The adenovirus used is one that mainly infects chimpanzees. When the adenovirus package delivers the code for the SARS-CoV-2 spike protein, the immune system can then train itself to recognize and destroy anything with the same spike protein—and that would be all SARS-CoV-2 viral particles, which are studded with spike proteins.

 

The AZD1222 results announced today come from a pooled analysis of clinical trials conducted in the United Kingdom and Brazil, involving over 23,000 participants. AstraZeneca’s independent monitoring board found AZD1222 was on average about 70-percent effective at preventing COVID-19, the disease caused by SARS-CoV-2. The interim analysis was triggered when 131 cases showed up in participants across the trials, who were given either two doses of AZD1222 or a comparator vaccine, the meningococcal vaccine MenACWY. The efficacy rate is calculated based on how those 131 cases split into the MenACWY group versus the AZD1222 group.

 

But the results were a little more complicated than that simple split. Participants who received AZD1222 got one of two dosing regimens, so the results were split further. In one regimen, participants were given a half-dose of AZD1222 followed by a booster shot with a full dose. In the trials, 2,741 participants got this regimen, and it appeared about 90-percent effective at preventing COVID-19.

 

In the other regimen, participants receiving AZD1222 got two full doses of the vaccine. In other words, they got the same high dosage level in their first shot as in their booster shot. In the trials, 8,895 participants got this regimen, and it appeared about 62-percent effective at preventing COVID-19.

 

The pooled efficacy data yields the average efficacy at around 70 percent. This is impressive, given a goal of around 50 percent. However, it’s not quite as high as the stunning mRNA vaccine efficacy results reported in previous weeks. Those included 95 percent efficacy for Pfizer/BioNTech’s vaccine and 94.5 percent efficacy for Moderna’s.

Unexpected result

AstraZeneca’s better result with the regimen starting with a half dose has already led to head scratching among experts. Most importantly, it’s unclear if the 90-percent efficacy result will hold up as AstraZeneca collects more data and conducts further analyses. We don’t yet know how the 131 cases split in the subgroup analyses. That final efficacy number is very likely to change as more data is collected. But, if that finding does hold up, some experts have already begun speculating as to why.

 

Several think it may be down to the adenovirus packaging. Though the vaccine is aimed at spurring immune responses against the SARS-CoV-2 spike protein carried by the adenovirus, some immune responses will inevitably attack the adenovirus itself. If the two-dose regimen starts out high, it may tip the immunity scales toward a stronger anti-adenovirus response rather than an anti-spike response when the booster shot is delivered. This is speculative, though, and understanding what's actually happening will require far more data.

 

On a positive note, needing less vaccine in the first dose—if that really does end up being the case—means more people can be vaccinated with the same amount of vaccine manufacturing capacity.

 

And on yet another positive—though very preliminary—note, the Oxford researchers reported that AZD1222 appeared to reduce asymptomatic infections with SARS-CoV-2. The primary analysis looked at symptomatic cases of COVID-19, but some participants in the trial were regularly screened for asymptomatic infection. This finding is particularly eyebrow-raising since the mRNA vaccine trials exclusively looked at only symptomatic COVID-19 cases. However, the finding is extremely preliminary as the researchers did not present any data on it.

Safety

As with the mRNA vaccines, AstraZeneca said no serious adverse events related to the vaccine “have been confirmed.” In earlier trial results, mild side effects from AZD1222 were common, including pain, feeling feverish, chills, muscle ache, headache, and malaise. Some participants were preemptively given paracetamol (acetaminophen/Tylenol) to lessen these effects.

 

If you’ll recall, AstraZeneca paused its trials at least twice, once in July and another in September, for standard safety reviews. Trials paused in July when a UK participant showed neurological symptoms and was later diagnosed with multiple sclerosis. In September, another participant developed symptoms in line with transverse myelitis—a condition involving inflammation of the spinal cord that can, in rare instances, be linked to vaccination. Both cases were eventually dubbed unrelated to the vaccine itself and the trials resumed.

 

Otherwise, no hospitalizations or severe cases of COVID-19 were reported in the study.

Delivery

A significant advantage to AstraZeneca’s adenovirus vaccine is that it is relatively easy to scale up production and doesn’t require specialized storage conditions. Adenovirus vectors are more established in the vaccine arena, compared with mRNA-based vaccines, which are brand-new. Manufacturing capacity to produce vast quantities of adenovirus already exists.

 

AstraZeneca noted in its press release that it is “making rapid progress in manufacturing with a capacity of up to 3 billion doses of the vaccine in 2021 on a rolling basis, pending regulatory approval. The vaccine can be stored, transported and handled at normal refrigerated conditions (2-8 degrees Celsius/36-46 degrees Fahrenheit) for at least six months and administered within existing healthcare settings.”

 

The mRNA vaccines require cooler storage conditions. Most notably, Pfizer and BioNTech’s vaccine requires storage at a troublesome -70°C. In a recent press release, Pfizer emphasized that the companies “developed specially designed, temperature-controlled thermal shippers utilizing dry ice to maintain temperature conditions of -70°C ± 10°C. They can be used as temporary storage units for 15 days by refilling with dry ice.” The vaccine can further be stored at normal refrigerated 2-8°C conditions for five days.

 

Pfizer and BioNTech are aiming to have up to 50 million vaccine doses in 2020 globally and up to 1.3 billion doses by the end of 2021.

 

Moderna announced in a recent press release that its vaccine remains stable for six months at -20° C (-4°F), up to 30 days at normal refrigerator temperature (2-8 degrees C or 36-46 degrees F), and up to 12 hours at room temperature. Moderna currently plans to have about 20 million doses of mRNA-1273 ready to ship in the US in 2020 and produce an additional 500 million to 1 billion doses globally in 2021.

 

All three vaccines are now headed to regulators worldwide for authorization. Pfizer submitted its request for an Emergency Use Authorization from the US Food and Drug Administration on Friday.

Unknowns

All three vaccines have yet to have their full datasets published, so much uncertainty remains about the data and analyses. The efficacy numbers will likely change as trials continue, safety monitoring grows longer, and peer reviewers look over the analyses. Rare side effects are also more likely to pop up as time goes on.

 

While preliminary studies on the vaccines suggested they all prompt a variety of immune responses in participants, how long any protection from any of these vaccines may last is completely unknown. It's still unclear what levels of immune responses equate to full protection from an infection or severe disease. And in a one-year-old pandemic with a completely new-to-us pathogen, it’s impossible to say with certainty how long those protective immune responses will stay protective.

 

Last, there’s so far no data on how well the vaccines protect against asymptomatic infections. Preventing disease—and in particular, life-threatening disease—is the top priority in these trials. However, preventing asymptomatic or mild infections will be key to putting an end to SARS-CoV-2 transmission overall.

 

 

AstraZeneca’s COVID-19 vaccine shows success: Here’s how it stacks up to others