November 23, 2020

expert reaction to phase 3 interim analysis of the Oxford/AstraZeneca COVID-19 vaccine

Oxford and AstraZeneca have announced that their vaccine candidate against COVID-19 has demonstrated 70.4% efficacy (when combining data from two dosing regimens) in the first interim analysis from the phase 3 vaccine trials.

This Roundup accompanied an SMC Briefing.

Comment updated 25/11/2020 Prof Paul Hunter, Professor in Medicine, UEA, said:

“It has been widely reported that the Oxford COVID-19 had an overall efficacy of just 70% compared to 90% for the Pfizer and Moderna mRNA vaccines. But those people who were given half the original dose for the first injection had an efficacy of 90% and this has become the headline figure in many reports. So the promising interim results of the Oxford vaccine are based on a subgroup analysis, the subgroup given the correct dose and the subgroup given an incorrect (half) dose according to protocol. The efficacy in those people receiving the correct dose according to protocol was only about 62% compared to over 90% found in the previously reported mRNA vaccine results.

“Subgroup analyses in randomised controlled trials are always fraught with difficulties. Subgroup analyses increase the risk of type 1 errors (i.e. where an intervention is considered to be effective when it is not). Despite the increased risk of type 1 errors, there are certainly arguments in favour of sub-group analysis in RCTs. However, any subgroup analysis should be specified in the protocol in advance and the RCT should be sufficiently powered for the sub-group analysis in order to have faith in the results. As Brookes and colleagues wrote in 2001 “While it is generally recognised that subgroup analyses can produce spurious results, the extent of the problem is almost certainly under-estimated” and “Subgroup-specific analyses are particularly unreliable and are affected by many factors”.

“The results of subgroup analyses are likely to be less precise, especially if, as appears to be the case here, that rather fewer people were recruited into the half dose rather than for the full dose regimens. We will have to wait final results to be reviewed by the appropriate regulatory authorities before we can be confident that the claim of 90% effectiveness with the half-dose regimen is robust.”

Reference: S T Brookes, E Whitley, T J Peters, P A Mulheran, M Egger, G Davey Smith. Subgroup analyses in randomised controlled trials: quantifying the risks of false-positives and false-negatives. Health Technology Assessment 2001; Volume 5, Issue 33, 1-49

Dr Julian Tang, Honorary Associate Professor/ Clinical Virologist, Respiratory Sciences, University of Leicester, said:

“This is more encouraging news on the COVID-19 vaccine development front.

“The differences in effectiveness for the Pfizer and Moderna mRNA (94-95%) and Oxford chimpanzee-adenovirus-vectored  (60-90% depending on dosing regimen) vaccines are currently based on the analysis of just 100-200 patients – when there are some 30,000-50,000 trial participants for each vaccine, so these figures could still change dramatically later on.

“However, whilst the Pfizer and Moderna vaccine Phase 3 effectiveness estimates have included a diverse range of participants from different ethnic groups, the Oxford vaccine participants have been mainly drawn from a white Caucasian population in their early trials. So more data on its effectiveness in BAME populations will be useful.

“Practically, the colder storage temperatures required for the long-term storage and transport of the Pfizer and Moderna mRNA vaccines may be an obstacle.

“This may become more pronounced when the other vaccines pre-ordered by the UK: Novavax and GSK/Sanofi (protein subunit), Janssen (adenovirus-vectored) and Valneva (whole virus inactivated) become available later on, which can all be stored at typical fridge temperatures (2-8 C), making them much easier to store, transport and administer.

“However, the mRNA vaccines may have an advantage over the adenovirus-vectored vaccines if annual boosters are needed. The development of host antibodies to the adenovirus-vector may limit these vaccines’ usefulness if such annual boosters are needed to maintain longer term protection.”

Prof Eleanor Riley, Professor of Immunology and Infectious Disease at the University of Edinburgh, said:

“If there is anyone out there who still doubts that a Covid-19 vaccine can help us out of this pandemic, the announcement today from Oxford University/Astra Zeneca should surely dispel that doubt. This is excellent news – another vaccine that can prevent symptomatic infections and, even better is cheap to produce and easy to distribute. Whilst we await further details on efficacy in older age groups and prevention of hospitalisation, this trial also has the potential to answer questions about virus transmission. In contrast to some other trials, the Oxford/Astra Zeneca team has been collecting weekly nasal and throat swabs from all trial participants to look for asymptomatic infections. If the vaccine reduces transmission – i.e. vaccinated individuals have fewer asymptomatic infections, or their viral load is lower if they are infected, or if they shed virus for a shorter period of time – the vaccine could make an important contribution to herd immunity”.

“It is important also to recognise that the ability of the scientific community to respond so effectively to the challenge of Covid-19 is not some happy accident. Developing these vaccines builds on decades of research to understand viruses, to understand the immune system, to sequence genomes and to manipulate DNA and RNA, and is complemented by years of applied research in bioengineering and bioprocessing. The Jenner Institute at the University of Oxford has been working on modified viral vaccines for more than 20 years; this success surely justifies their persistence and determination and the continued investment of public funds.

“If the general public, and politicians, require a justification for long-term investment in scientific research across the entire landscape from fundamental discovery to translation and application, this is surely it.”

Dr Zoltán Kis, Research Associate at the Future Vaccine Manufacturing Hub, Imperial College London, said:

“This is very promising news regarding yet another vaccine for Covid-19. The AZD1222 is a replication-deficient chimpanzee adenoviral vectored vaccine. This means that the chimpanzee adenovirus, which cannot replicate in human cells, is used to deliver the genetic material of the vaccine (in the form of DNA) into the cells of the human body. Once delivered into the cells, the DNA of the vaccine is translated into RNA and from the RNA the protein antigen is produced using the natural gene expression mechanisms from the cells. Thus, both the adenoviral vectored vaccines and the RNA (mRNA and saRNA) vaccines contain instructions based on which the cells of the human body produce the antigen of the vaccine. This antigen then induces an immune response to train the body to fight the SARS-CoV-2 virus.

“Adenoviral vectored vaccine production is more established, and production processes are already implemented at a larger scale compared to the RNA (both mRNA and saRNA) platforms. However, adenoviral vector-based vaccine production is more time-consuming than RNA vaccine production. This is because adenoviral vector-based vaccines are produced using mammalian cells which grow slowly, whereas RNA vaccines are produced using a cell-free production process based on a rapid enzymatic DNA-templated reaction. Due to this faster production process, a greater number of doses of RNA vaccines (in particular saRNA) could be produced in much smaller facilities within the same time period compared to adenoviral vectored vaccines.

“The amount of active ingredient (aka drug substance) per dose of the adenoviral vectored vaccine (measured in viral particles per dose) is not directly comparable to that of mRNA or saRNA vaccines (measured in micrograms of RNA per dose).

“The AZD1222 vaccine candidate has the advantage that it can be distributed and stored at temperatures between 2-8 degrees Celsius. In addition, AZD1222 is available at a lower purchase price than the mRNA vaccines which are currently in late-phase clinical development. This makes the AZD1222 vaccine candidate a more viable option for low- and middle-income countries. By lowering the amount per dose of RNA (both mRNA and saRNA) vaccines and by further improving this new technology, it is expected that the thermostability of RNA vaccines will increase and production costs decrease.  Therefore, RNA vaccines could become optimal for rapid-response and large-volume manufacturing at a low cost.”

Dr. Richard Hatchett, CEO of CEPI, said:

“This is very encouraging interim efficacy data which indicates that we can expect this vaccine to have a significant impact on public health wherever it is used. 

“We believe that this vaccine candidate has the potential to significantly alter the course of the global pandemic. The data released today suggest the vaccine is safe and comparable in its efficacy to other licensed vaccines – including influenza – that are widely used to protect people around the world today.

“AstraZeneca and Oxford have developed an affordable, scalable vaccine that crucially can be stored and shipped in a regular refrigerator.  This makes it appropriate for use and easy to deliver almost anywhere in the world, including in low-resource settings.  That means that this vaccine will make an important contribution to controlling the pandemic globally. 

“Following the recent positive news about the mRNA vaccine candidates, it is terrific to see another approach to vaccine development also yielding such positive findings on an interim analysis. The world urgently needs multiple safe and effective vaccines to control the pandemic in a range of populations and settings, so the success of this viral vector vaccine would be a significant step towards that goal. 

“We are proud that CEPI has played an important role in developing and enabling global access to this vaccine candidate. Our support for this vaccine builds on CEPI’s long-standing partnership with the University of Oxford to advance the development of the underlying technology. When COVID-19 emerged, CEPI was funding Oxford to develop vaccines against MERS, another coronavirus, and other emerging infectious diseases using this vaccine approach.  

“The learning and data from these programmes gave the Oxford team a head start when COVID-19 emerged, and CEPI then provided catalytic investments to fund preclinical work and manufacture materials for the Phase 1 trial of this vaccine candidate, helping the work to proceed at pace.  

“In June we partnered with AstraZeneca to scale up manufacturing capacity, which has secured 300 million doses of the vaccine for global distribution through the COVAX Facility.

“We are extremely encouraged by the results announced today and wish to congratulate the teams at AstraZeneca and the University of Oxford on the development of a vaccine that, if approved, will contribute critically to global control of COVID-19.”

Dr Colin Butter, Associate Professor and Programme Leader in Bioveterinary Science, University of Lincoln, said:

“News from the trial of Oxford’s Covid 19 vaccine, ChAdOx1 nCoV-19, is extremely encouraging.  The trial included a number of different dosing regimens, with a second “boost” dose given a month after an earlier “prime” dose.   Whist the trial data are not yet published, the press release indicates  that these gave efficacies of 90% and 62%.  The headline figure of 70.4% is the overall efficacy of the entire trial.

Optimisation of prime boost strategies with these recombinant vaccines, where a harmless virus is used as  a “Tojan Horse” to introduce genetic material from the target virus, is complex and usually achieved experimentally: a luxury not available in the present situation.  However, should the data be sufficient to support regulatory approval of the 90% efficacious “low dose prime, high dose boost”  strategy then this vaccine offers a clear pathway out of the present pandemic and advantages over the two vaccines that have presently reported.  Firstly, it requires only a conventional cold chain, used for many products by every surgery and pharmacy in the county.   Secondly, although the manufactures have not reported the number of doses presently available, this is believed to be many tens of millions in the UK alone: a reduced priming dose further reduces the actual requirement.  Lastly, the trial provides evidence that the vaccine reduces not only clinical disease but also onwards transmission, giving the possibility of achieving heard immunity.”

 Prof Peter Piot, Director of the London School of Hygiene & Tropical Medicine, said:

“2020 will be remembered for the many lives lost from COVID-19, lockdowns and the US election. Science should now be added to this list.

“Breakthroughs in science are nothing new, but the importance of the three announcements this month from Pfizer/Biontech, Moderna and today from University of Oxford-AstraZeneca cannot be overestimated.

“The pandemic has taken lives and livelihoods all around the world, turning our way of life upside down in ways we never thought would happen and crippling economies in the process.

“The only way to stop COVID-19 in its tracks is having multiple effective and safe vaccines that can be deployed all around the world and in vast quantities.

“I am very pleased to see 62% to 90% efficacy, depending on the doses used, for the Oxford-AstraZeneca COVID-19 vaccine. The encouraging news is that greater protection at lower dose may mean that more people can be vaccinated with the same amount of vaccines, and that this vaccine can be stored easily at regular fridge temperature. This will also help with equitable access all over the world. I eagerly await to see the data and their implications for deployment of vaccines against COVID-19.

“However, there are still many hurdles to cross before this pandemic is under control and we can return to normal life. Most importantly, we must all continue to follow the rules for safe behaviour to suppress the spread of SARS-CoV-2 and save as many lives as possible until we see the full and widespread impact of vaccination. At the same time, urgently addressing vaccine hesitancy is vital.

“However, November 2020 looks set to be the month that humanity developed the tools to turn the tide against this devastating virus.”

Prof Sheila Bird, Formerly Programme Leader, MRC Biostatistics Unit, University of Cambridge, said:

“Two late phase trials of ChAdOx1 nCoV-19 are referred to in the press-release by AstraZeneca: one in UK (12,400 participants analysed, to nearest 100), the other in Brazil (10,300). The trials were designed somewhat differently: for example, the vaccine trial in Brazil seems to have compared two full doses of ChAdOx1 nCoV-19 versus vaccine-control, whereas the “half-dose, full dose” regimen is a feature of the UK trial. Design-differences explain, in part, why the number who received the “half-dose, full dose” regimen is only 24% of those who were randomized to ChAdOx1 nCoV-19 (2,741/11,636). As details matter, such as within-country controI group, I shall refrain from further comment until the paper is available to read.”

Prof Ravindra Gupta, Professor of Clinical Microbiology, University of Cambridge, said:

“The data from the Oxford vaccine are welcome and follow on from the recent publication of findings on the immune responses generated in both young and older individuals. The significant difference between the two doses in the present study highlights the importance of conducting such trials. There were 130 infections detected overall, providing significant confidence in the findings. Of note this study tested participants for asymptomatic infection, in contrast to other recently reported vaccine studies. It is unclear what proportion of infections were associated with symptoms from the press release. An important advantage of this vaccine is the compatibility with existing refrigeration practices.”

Dr Charlie Weller, Head of Vaccines at Wellcome, said:

“The preliminary results from the University of Oxford/AstraZeneca vaccine team are hugely encouraging. These results suggest it is highly effective in protecting serious illness and it may reduce transmission. It is based on an established vaccine technology, which does not require the challenging cold-chains and should therefore ease deployment and global access. As with all interim results we have seen, it is critically important that the trial is completed and regulators can now independently and rigorously assess the data.

“Vaccines, treatments and tests are all vital to protect lives and end this pandemic as soon as possible. To have interim results from three vaccine teams within a year is incredible, and testament to a truly extraordinary global scientific effort. We need a range of vaccines, that can protect people of different ages and backgrounds wherever they live, and to be able to manufacture enough doses for the world. To meet the aim of vaccinating high-risk populations around the world over the next year we need at least 2 billion vaccine doses.

“Beating Covid-19 will depend on global collaboration. It was encouraging at the weekend that G20 countries pledged to ensure fair access for Covid-19 vaccines, treatments and tests. Promises must be followed by action to ensure equitable distribution and with a significant step-up of investment. The incredible scientific progress being made will be for nothing if global governments do not make more money available and urgently. Investing in the ACT-Accelerator is the most viable global solution to enable countries to transition out of the current crisis.”

Dr Gillies O’Bryan-Tear, Chair, Policy and Communications, Faculty of Pharmaceutical Medicine, said:

“Today we see the eagerly awaited interim results of the Oxford/AstraZeneca Covid-19 vaccine trial: the investigators report over 70% efficacy in preventing symptomatic Covid illness amongst the 24,000 trial participants. These are very positive results when we recall that the hurdle for a good enough vaccine was set at 50-60%, in line with the flu virus. This is a two dose, adenoviral vector vaccine, different from the two mRNA vaccines already announced, and similar to the Russian Sputnik vaccine, except that in the latter, a different vector is used for the prime (first dose) and boost (second dose) vaccine. 

“Herein lies a clue to one interesting finding from this study, which is that the group reports 90% efficacy in a subgroup who received half the standard dose as the prime dose, with a normal boost dose. The efficacy in the group who received the standard dose for both prime and boost was 62%. One potential explanation for this is that the body is mounting an anti-vector immune response to the second dose, which is lower if the first dose is reduced;  such an immune reaction could reduce the efficacy of the vaccine. We have seen over 90% efficacy with the mRNA vaccines which would not be subject to this effect, and the Russian vaccine also reported 90% efficacy – supporting the theory about an anti-vector antibody. 

“Peer-reviewed, detailed safety data from the smaller Phase 2 trial were published last week in the Lancet, and we await the safety results from this larger study. 

“The group also report that there was evidence of an effect on preventing viral transmission – these data, if positive, would be very important if confirmed. Having said that, most observers believe that if the vaccines prevent illness, they will also prevent transmission to a greater or lesser extent. 

“The great advantage of this Oxford vaccine over the mRNA vaccines is that it can be manufactured easily and transported at ordinary fridge (not freezer) temperatures, so can be transported and stored using the existing vaccine cold chain infrastructure. The group has promised to provide the vaccine not-for-profit to developing nations. 

“The level of efficacy seen with this vaccine is well over the threshold set for these vaccines, and at the threshold required for herd immunity provided there is sufficient take-up. It is unquestionably more good news for the Covid pandemic, and given its much lower price than the mRNA viruses, this could be the vaccine that reaches more parts of the global community than the mRNA vaccines.”

Dr Zania Stamataki, Viral Immunologist, University of Birmingham, said:

“More good news from the Oxford vaccine with up to 90% efficacy (combined efficacy from various doses was 70%). People will be tempted to compare efficacy between the different vaccines but we must remember that these are early data designed to achieve approval. Efficacy is not the same as effectiveness and the early numbers will change as the vaccines are rolled out. 

“It is important to pinpoint the parts of the immune response responsible for protection, so we can refine vaccines for higher potency. 

“Having a choice of vaccines less than a year after the new coronavirus jumped to humans is a remarkable achievement and we must learn from this to use the new infrastructure against other diseases.”

Dr Ayfer Ali, Associate Professor of International Business at Warwick Business School and an expert on the pharmaceutical industry, said:

“While the overall results for this new vaccine are not as good as those disclosed earlier this month, they clearly show protection. That is excellent news, as at this point we need as many vaccines as possible to vaccinate the global population.

“It is also possible that the stage adjustments may give us results comparable to the mRNA vaccines. It is important to remember that all these results are preliminary and subject to change when the full trial results are available.

“This vaccine does have benefits over the other two in terms of distribution. The more flexible storage conditions for this vaccine will lower vaccine waste due to occasional cold chain distribution system failures which are inevitable with the other mRNA vaccines.

“This will also use our existing vaccine distribution infrastructure without adjustments. It will be particularly suited for developing regions both because of the lower costs and the easier storage and distribution.”

Professor Dame Ottoline Leyser, Chief Executive, UK Research and Innovation, which helped to fund the vaccine, said: 

“It’s a Herculean achievement in under a year and a tribute to the dedication of many people – from scientists and clinicians in universities and industry to the trial volunteers – who have come together to deliver this promising vaccine with tremendous speed.

“These preliminary Phase III results show the Oxford-led COVID-19 vaccine could be more effective against coronavirus than typical vaccines against seasonal flu, but more study is needed to understand dosing and the protective response from the vaccine.

“We are proud to have supported this promising and inexpensive vaccine, which could be easily distributed at fridge temperature and administered by healthcare systems worldwide.”

Prof Stephen Evans, Professor of Pharmacoepidemiology, London School of Hygiene & Tropical Medicine, said:

“This is good news, even if not as exciting as the news from the mRNA vaccines.

“It is likely that on one dosing regime (from my calculation based on information in the press release rather than what AZ said directly) is that with the smaller group (half/full) there were 3 cases of confirmed Covid 19 in the 2741 giving the vaccine and 29 cases in about the same number given the control (a Meningitis vaccine or placebo). This gives an efficacy close to 90% as reported. In the two full dose regime there were probably 27 cases of Covid in the vaccine group out of 8895 given it, while there were probably 72 cases in the control group. This gives an efficacy close to 62% as reported and combining the data across both groups gives an average of 70.2%. There are statistical uncertainties in each of these numbers and the overall results has a lower bound of over 50% which was a criterion mentioned as being of importance to regulators. There is little doubt that these data meet the criteria, based on numbers alone, for regulatory approval. Regulators will scrutinise all the detailed data before giving approval.

“The really good news is twofold. Firstly the vaccine can be stored in ordinary refrigerators, which helps in high-income countries but is of enormous importance for low-income countries. Secondly, the manufacturers and Oxford are committed to making it as easy as possible, through the WHO COVAX agreements, for the vaccine to reach low and middle income countries with their pledge to provide the vaccine at cost to such countries not just for the duration of the pandemic but indefinitely.”

Professor Deborah Dunn-Walters, Chair of the British Society for Immunology COVID-19 and Immunology taskforce, and Professor of Immunology at University of Surrey, said:

“Today’s announcement on interim phase 3 trial results of the University of Oxford/AstraZeneca COVID-19 candidate vaccine, ChAdOx1 nCoV-2019, are a positive step forward, although we need more data to be able to accurately assess the findings and implications.  This vaccine has already been through many carefully monitored stages of clinical trials to assess its safety and effectiveness, with this phase 3 trial being the largest and most in depth of those.  During this part of the trial, the Oxford team will have examined lots of different parameters around the safety and effectiveness of the vaccine, including the dosing schedule. Intriguingly, the team report a higher efficacy of up to 90% when using a halved first dose and standard second dose and report that the vaccine could be effective in preventing disease transmission as well as disease itself.  These are both very promising indications but again, we need to see the complete dataset to analyse the full implications for different sectors of the population.  We await the full trial results with anticipation. 

“An additional benefit of this University of Oxford/AstraZeneca COVID-19 vaccine is the fact that it can be stored safely at temperatures found in a normal domestic fridge (2-8°C), making global rollout a much easier logistical challenge.

“The researchers working on this vaccine, both in the UK and globally, should be applauded for the monumental effort they have put in to move the science forward at such a fast rate. In the quest to find vaccines and therapeutics against SARS-CoV-2, we must continue to support our research community to maximise our knowledge of this disease. The UK leads the world for the quality of our immunology research and this is another great example of how the community has come together to drive forward scientific discovery into this pandemic.”

Dr Penny Ward, Visiting Professor in Pharmaceutical Medicine at King’s College London and Chair of the Education and Standards Committee of the Faculty of Pharmaceutical Medicine, said:

“It is good news that a third vaccine has been shown to be highly effective in preventing COVID-19 disease and that this might be achieved using a dose regimen which enables available doses to be administered to a higher number of people. The vaccine can also be stored and transported using a refrigerated supply chain, which is less onerous than requiring frozen shipments. The University of Oxford statement includes the tantalising phrase ‘ Early indication that vaccine could reduce virus transmission from an observed reduction in asymptomatic infections’. If this observation is borne out it is an important additional finding which suggests that in future local outbreaks could be managed via rapid ‘ring vaccination’. Insufficient information is available to enable an understanding of the reported differences between the dose regimens investigated. In addition, although the total safety database size is reported to comprise 24,000 subjects (a tad smaller than the populations exposed to the mRNA vaccines reported earlier in the month) no information is provided on the safety profile observed. The recent Lancet publication of the Phase II data suggested that immediate adverse effects are limited to injection site reactions and mild flu like illness which are easily managed with paracetamol/ibuprofen. The detailed publication, said to be in preparation in parallel with regulatory submissions, is eagerly awaited.”

Prof Peter Openshaw, Professor of Experimental Medicine at Imperial College London, said:

“These preliminary results are impressive and add to optimism that we can use vaccination to prevent COVID-19. The Oxford/AZ vaccine dosage was chosen as one that gives acceptable side effects and a half-dose starter dose is great news, if confirmed once all the data has been reviewed.  

“The report that an initial half-dose is better than a full dose seem counterintuitive for those of us thinking of vaccines as normal drugs: with drugs, we expect that higher doses have bigger effects (and more side-effects), but the immune system does not work like that.

“The report that an initial half-dose then a full dose is even better than two full doses is great news, potentially increasing the number of people that can be vaccinated and reducing costs.”

Prof Ian Jones, Professor of Virology, University of Reading, said:

“The positive outcome for the Ox/AZ vaccine was to be expected from the phase 3 results shown recently for other vaccines but the data is not quite as clear cut as might have been hoped for. The reduced efficiency of the 2 full dose regimen could relate to immunity to the vector, which might indicate that for Adenovirus vectored vaccines the 2 serotype approach of the Sputnik V vaccine has advantages, but we must wait for the full published data for both trials to see if this is indeed the case. There is no vector in either the BioNtech/Pfizer or Moderna vaccines so the issue of immunity to the vector does not arise. The safety profile and storage aspects are both positive, as is the commitment to its no-profit release.”

Dr Stephen Griffin, Associate Professor in the School of Medicine, University of Leeds, said:

“This is yet more excellent news and should be considered tremendously exciting. The Oxford vaccine, as for the others we’ve heard about recently, is capable of generating 90% protection against COVID-19. Given the favourable stability seen for this vaccine, it has great potential to be delivered across the globe, achieving huge public health benefits.

“The overall figures are slightly reduced as they represent two dosing schedules combined, but this is simply a matter of sticking to the more efficient regimen. It may seem confusing that a higher initial dose gives a less favourable response, but this may just be due to a residual response in some patients to the disabled “vehicle” chimpanzee adenovirus used to deliver the vaccine “payload”, easily fixed by using the adjusted dose. It is important to note that this is in no way linked to any concern relating to vaccine safety.

“Whilst we are all eagerly awaiting the full data, including efficacy across age groups, vulnerable patients and whether infection is prevented compared to severe symptoms, we can all be encouraged by yet another leap forward in the strategy to deal with this pandemic. Nevertheless, whilst this prepares us for the next potential wave of infection, we must remain vigilant and resilient during the ongoing crisis.”

Prof Azra Ghani, Chair in Infectious Disease Epidemiology, Imperial College London, said:

“Once again we are waking up on a Monday morning to further good news about a COVID-19 vaccine. The results from this trial of the Oxford/AZ vaccine are highly encouraging demonstrating significant efficacy. A particular strength of this vaccine is that it can be stored in a fridge; this means that it can be distributed around the world using existing delivery mechanisms. This could therefore have a truly significant impact across the globe and enable an end to the COVID-19 pandemic.

“Of course much will be made of the difference in overall efficacy between this vaccine (70%) and the Pfizer and Moderna vaccines (95%). However, it is encouraging to see that in a sub-analysis, a fractional dosing schedule in which the first dose was administered at a lower level than the second resulted in higher efficacy and gave results comparable to the other vaccines (90%).  It will be important to both understand the mechanisms generating this result as well as to confirm this in the final efficacy analysis. If this result holds, this will mean that the same manufacturing capacity will be able to produce more doses and thus further reduce the constraints on vaccine supply.

“It is also important to note that differences in efficacy may be due to the length of follow-up of participants across the three trials. Both the Pfizer and Moderna vaccines trials began recruitment at the end of July whereas the Oxford/AZ trial began recruitment in May. Once final data are available across all three trials, it would be helpful to undertake a combined analysis to fully understand any differences in efficacy across difference population groups.”

Prof Peter Horby, Professor of Emerging Infectious Diseases and Global Health in the Nuffield Department of Medicine, University of Oxford, said:

“This is very welcome news, we can clearly see the end of tunnel now. There were no COVID hospitalisations or deaths in people who got the Oxford vaccine. Although no serious reactions were reported in people who got the Oxford vaccine, we do need to await the full safety data and to monitor safety of all vaccines carefully if and when they are rolled out. The reported efficacy of 70% is an interim measure and as more data accrue we will get a better idea of the protection it affords. Importantly, from what we have heard the vaccine seems to prevent infection not just disease. This is important as the vaccine could reduce the spread of the virus as well as protect the vulnerable from severe disease. The Oxford vaccine can be stored in the fridge, as opposed to the freezer like the other two vaccines, which means it is a more practical solution for use worldwide.”

Dr Michael Head, Senior Research Fellow in Global Health, University of Southampton, said:

“We have further exciting news that vaccine development is proving successful. These results are intriguing, with two different estimates of efficacy depending upon the dose used with the vaccine. These are provisional results that have not been peer-reviewed and the study is ongoing, so as with the other recent announcements from Pfizer and Moderna, we should be a little cautious about these findings. It’s not yet fully clear why a half dose and then a full dose was potentially more protective but if the final results continue to show this pattern of around 90% effectiveness, this would allow greater vaccine supply not just in the UK but also globally.

“The published phase 2 trial results showed a protective effect in older populations which is important for high-income populations where elderly groups have been particularly badly affected by COVID-19.

“This vaccine candidate also requires refrigeration storage rather than the ultra-low temperatures of the Pfizer candidate. Oxford have previously confirmed that there would be some level of distribution to low-and-middle-income countries so this may also be good news around the subject of equitable access to vaccine development with a product that is much easier to store and distribute. The pandemic is everyone’s problem at least until the vast majority of the globe is vaccinated, not just the rich countries.”

Reference re Oxford and equitable distribution- https://www.ox.ac.uk/news/2020-06-05-oxford-university-s-covid-19-vaccine-next-steps-towards-broad-and-equitable-global

Oxford press release – https://covid19vaccinetrial.co.uk/sites/default/files/covid19vaccinetrial/documents/media/201123_press_release.pdf

AstraZeneca press release – https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2020/azd1222hlr.html

All our previous output on this subject can be seen at this weblink:

www.sciencemediacentre.org/tag/covid-19

Declared interests

Prof Eleanor Riley: “Prof Riley is a member of the UK Vaccines network and the UKRI Covid-19 Taskforce.”

Dr Zoltán Kis: “No conflicts of interest to declare.”

Dr. Richard Hatchett: “CEPI has funded the University of Oxford and AstraZeneca’s COVID-19 vaccine programme.”

Dr Colin Butter: “I have worked with Professor Gilbert on the use of similar recombinant viruses in the control of influenza in humans and birds.”

Prof Peter Piot: “LSHTM Director, Special Advisor to EC President von der Leyen, Board Member CEPI.”

Prof Ravindra Gupta: “No conflicts of interest.”

Dr Charlie Weller: “Wellcome co-founded and co-funds CEPI, which has provided support to the development and manufacture of the University of Oxford/AstraZeneca AZD1222 vaccine candidate.”

Dr Gillies O’Bryan-Tear: “No conflicts.  Former Head of Vaccine Clinical Development, GSK.  I am a pharmaceutical physician, semi-retired and have worked in a variety of fields, including oncology (cancer) drug development and vaccines development.  I have not been active in vaccine research for many years and have no current interests in or conflict with any of the Covid-19 vaccine research programmes.”

Dr Zania Stamataki: “No conflict of interest with any of the vaccine studies.”

Dr Ayfer Ali: “No interests to declare.”

Professor Dame Ottoline Leyser: “UKRI was a funder of this vaccine.”

Prof Stephen Evans: “No conflicts of interest. I am funded (one day per week) by LSHTM. They get funding from various companies, including Astra Zeneca and GSK but I am not funded by them, I have no involvement in obtaining funding from them and I am not an investigator on any grants obtained from them. I am the statistician to the ‘meta-Data Safety and Monitoring Board’ for CEPI. I am paid for my attendance at those meetings and will be paid expenses for travel if that occurs.”

Professor Deborah Dunn-Walters: “No interests to declare.”

Dr Penny Ward: “No COIs. I am semi-retired, but I am owner/Director of PWG Consulting (Biopharma) Ltd a consulting firm advising companies on drug and device development.  Until July 2019 I was Chief Medical Officer of Virion Biotherapeutics, which was a company developing broad spectrum RNA therapy for the treatment/prevention of respiratory virus infections.  Between December 2016 and July 2019 I served as Chief Medical Officer of Virion Biotherapeutics Ltd, a company developing antiviral treatments for respiratory viral diseases.  Previous employee of Roche, makers of tocilizumab (anti IL6 antibody) and CMO of Novimmune, makers of empalumab (anti IFN gamma antibody).”

Prof Peter Openshaw: “Peter Openshaw has acted as consultant, panel member or scientific advisor to GSK, Janssen (J&J) and Pfizer. These have not been specifically on COVID, but involve vaccine and antiviral compounds that might be effective against RSV or influenza.”

Prof Ian Jones: “No conflicts.”

Dr Stephen Griffin: “No conflicts.”

Prof Azra Ghani: “I don’t think I have any conflicts, but note that I am providing advice to WHO and WHO-Europe on vaccine modelling to support allocation.”

Prof Peter Horby: “I am co-Chief Investigator of the RECOVERY trial. The RECOVERY trial is supported by a grant to the University of Oxford from UK Research and Innovation and NIHR (MC_PC_19056 ). Tocilizumab was provided free of charge for this study by Roche. Lopinavir–ritonavir was provided free of charge for this study by Abbvie.  REGN-COV2 was provided free of charge for this study by Regeneron.

“I am an employee of University of Oxford with salary supported by Wellcome Trust and NIHR.

“I do not accept any personal honoraria payments directly or indirectly from the pharmaceutical, biotechnology, or food industries.”

Dr Michael Head: “The University of Southampton is one of the trial partners, but I am not involved in the trial.”

None others received.