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EXPERT REACTION: Scientists call for pause to AstraZeneca vaccine rollout

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The Australian and New Zealand Society for Immunology says the federal government should immediately pause the planned rollout of the AstraZeneca vaccine because it may not be effective enough to generate herd immunity. Below, Aussie scientists respond to the pause request.

Organisation/s: Australian Science Media Centre

Funder: N/A

Expert Reaction

These comments have been collated by the Science Media Centre to provide a variety of expert perspectives on this issue. Feel free to use these quotes in your stories. Views expressed are the personal opinions of the experts named. They do not represent the views of the SMC or any other organisation unless specifically stated.

Emeritus Professor Gregory Tannock is from the Burnet Institute

I have the following theoretical concern about the likely long-term efficacy of the Astrazeneca vaccine:

1. The same adenovirus vector with the same C-DNA COVID-19 inserted spike gene is present in both the first and second  doses. Would not the  secondary response to the much larger and highly immunogenic vector be likely to inhibit the response to the spike antigen?

2. Were developers of the Astrazenica vaccine aware of  a similar vaccine developed in Russia (the Sputnik V vaccine) in which a different adenovirus serotype was used as the vector for the second dose? Is there any reason why  this was not done? It certainly was not commented on, as  far as I am aware in Australia

Last updated: 13 Jan 2021 5:26pm
Declared conflicts of interest:
None declared.
Associate Professor Linda Selvey is from the School of Public Health in the Faculty of Medicine at the University of Queensland

The published data on the efficacy of the AstraZeneca (Oxford) vaccine involves relatively small numbers of subjects and a number of different dosing regimens. In particular, there were very few participants who were over 55 years old. One particular dosing regimen (low dose followed eight weeks later by a higher dose) demonstrated higher efficacy in preventing symptomatic COVID-19 infection (90 per cent efficacy), although, because of small numbers of participants who received this dosage regimen, this estimate is not very precise.

The standard dosage regimen has an efficacy of 62 per cent, again an imprecise estimate. As the vaccine did not demonstrate efficacy against infection, the concept of herd immunity cannot be applied to this vaccine given the available data. This is because herd immunity depends on protection against transmission. As COVID-19 can be transmitted by people not displaying any symptoms, it is necessary for vaccines to demonstrate protection against infection in order to result in herd immunity.

From the available data, it would appear that the AstraZeneca vaccine will likely play a role in reducing the risk of symptomatic infection in younger individuals. It would appear from the trial that the particular dosage regimen, including timing of the second dose, is not yet optimised, and further information is required before the vaccine can be fully assessed.

Given that Australia has the luxury of having minimal transmission of COVID-19 in the community, this points to the importance of awaiting further evidence before determining the optimal use of this vaccine in Australia. As there is insufficient data on the efficacy of the vaccine in people over the age of 55 years, the vaccine could be used to protect against symptomatic infection in younger individuals.

Last updated: 13 Jan 2021 1:06pm
Declared conflicts of interest:
None declared.
Hassan Vally is an Associate Professor in Epidemiology at Deakin University

Whilst we have to be flexible and we have to respond to the latest evidence when it comes to vaccines, I think we also have to be very careful and not overreact when we get new evidence. Whilst theoretically, all things being equal, a vaccine with a better efficacy is more advantageous than one with lower efficacy, if there is one thing that we’ve learned over the past year it is that we are not living in a theoretical world. We are living in the messy real world where there are practical and logistical considerations, where there is a great deal of uncertainty, our knowledge is changing daily, and all things aren’t equal.
 
Firstly, it’s worth highlighting that our current plan of using the Pfizer vaccine with reported 95 per cent efficacy, which will be the first available to us, to vaccinate high-risk groups makes perfect sense. This is going to be a huge step forward in terms of protecting the health of the community. Secondly, it's worth noting that the AstraZeneca vaccine is a good one and in the context of a worldwide pandemic it is an effective option. It exceeds the World Health Organization’s criteria for an effective vaccine with an efficacy of over 50 per cent. Further to this, it is a huge advantage that we can produce the vaccine onshore and guarantee the supply chain at a time when there are going to be vaccine supply issues globally. It's also important that the vaccine can be stored and transported safely at normal refrigeration temperatures.
 
There is no doubt there will be some changes made to the vaccination strategy as new vaccines become available, and we learn more about the properties of the current vaccines as they are administered to the larger numbers in the population and as we monitor whether immunity is maintained over longer time periods. However, we do need to be measured in our response to this latest data and also understand that the AstraZeneca vaccine is a safe and effective option that is going to make a huge difference if we can deliver this effectively and quickly to the Australian population.

Last updated: 13 Jan 2021 1:04pm
Declared conflicts of interest:
None declared.
Prof Bruce Thompson is the Head of the Melbourne School of Health Sciences at The University of Melbourne

Population-based vaccination for the SARS-COV-2 virus is a long game. There are only a few vaccines that are ready for roll-out, and many more are in the pipeline. The AstraZeneca vaccine would seem to be not as efficacious as others. However, that in no way suggests it is not part of the panoply of vaccines that are currently available or in the future. It is true that if a vaccine isn’t as efficacious then more people will need to be vaccinated to achieve herd immunity, however that is just one piece of the jigsaw.

Last updated: 13 Jan 2021 1:03pm
Declared conflicts of interest:
None declared.
Dr Abrar Chughtai is a Senior Lecturer and the Director of the Master of Infectious Diseases Intelligence Program at the School of Population Health, University of New South Wales Australia

This is really a tricky situation. Should we start immunisation with a vaccine with low efficacy (~70 per cent) now or wait for a few more months for a high efficacy vaccine (~95 per cent). I think at this stage the best strategy will be to go ahead with AstraZeneca/Oxford vaccine due to following reasons. 

Overall efficacy of AstraZeneca/Oxford vaccine is reasonable, i.e. around 70 per cent, but in a sub-group who were given a lower dose regime, the efficacy rose to 90 per cent. The main goal here is to achieve 'herd immunity', also known as 'population immunity'. Although there is limited evidence, some studies show that, to control epidemics, vaccine efficacy has to be at least 60 per cent when coverage is 100 per cent and at least 80 per cent when coverage drops to 75 per cent. So, if we use AstraZeneca vaccine, a higher coverage will be required, which may be a challenge but achievable. 

The AstraZeneca/Oxford vaccine is very cheap compared to the other two [vaccines] and storage and transportation are easy, which are important for vaccination programs. The UK is also using the AstraZeneca/Oxford vaccine for most of its citizens. The World Health Organization (WHO) has also accepted the AstraZeneca/Oxford vaccine and recently signed a purchase agreement with AstraZeneca for 170 million doses of the AstraZeneca/Oxford for COVAX. 

Most people agree that herd immunity must be global, so anyway, we will not able to control COVID-19 during 2021. The WHO's chief scientist also recently stated that herd immunity to the coronavirus would not be achieved in 2021, despite the growing availability of vaccines. 

Though there is limited data on duration of vaccine-induced immunity, most likely it will last for around one year and we have to vaccinate again. So, we can go ahead with AstraZeneca/Oxford vaccine this year and wait for more evidence. AstraZeneca/Oxford vaccine efficacy of ~70 per cent is reasonable to protect healthcare workers and other vulnerable groups. AstraZeneca is doing more studies and results will be available soon. If half dose of AstraZeneca/Oxford vaccine could trigger a greater immune response (with ~90 per cent efficacy), then this vaccine could be provided to more people. If more studies show less efficacy, then next year other vaccines may be purchased. We also need to keep an eye on the new COVID variant in UK, which is more transmissible. If this new variant becomes the dominant strain in Australia in the future, then we will definitely need a highly effective vaccine to achieve herd immunity.

Currently, there is a high demand for the other two vaccines, and it may not be possible to arrange those in a short period of time. We need to be pragmatic and also need to consider contract obligations and other government level commitments.

Last updated: 13 Jan 2021 1:02pm
Declared conflicts of interest:
None declared.
Dr Roger Lord is a senior lecturer (Medical Sciences) with the Faculty of Health Sciences at The Australian Catholic University and Visiting Research Fellow with The Prince Charles Hospital (Brisbane)

Last year reported efficacy values for several of the COVID-19 vaccine candidates under trial were all above 90 per cent. In each case this information was based on very small numbers of individuals who received one of the vaccines considered, and before any peer review of results was possible.

In December 2020, The Lancet reported the efficacy for the Oxford-AstraZeneca COVID-19 vaccine was 62.1 per cent with two standard doses of the vaccine. Trial results also indicated differences between efficacy and immunogenicity with the implication that immunological correlates of clinical protection may not exist for the vaccine.

Basically, the efficacy achieved for one cohort of individuals cannot be extrapolated to under-evaluated ages or other populations and so further bridging trials are required. Concern has also been raised that a 62.1 per cent efficacy will not be effective to develop herd immunity and that use of the Oxford-AstraZeneca vaccine should be halted in Australia.

This approach seems premature given the short-term goal is the ability of the vaccine to reduce viral transmission and infection. The largest part of Australia’s COVID-19 vaccine program involves 53.8 million doses of the Oxford-AstraZeneca vaccine. This vaccine does not require ultra-low temperature freezers for storage, is not as expensive as the two mRNA vaccines (Pfizer and Moderna), and has no reported serious adverse events or deaths with use.

Vaccine efficacy is important but so is community acceptance, logistics of delivery, length of protection, safety and economic feasibility. 

Improved efficacy may be achieved in further trials examining different patient cohorts, dosage regimes and better understanding of the infection.

Last updated: 13 Jan 2021 12:59pm
Declared conflicts of interest:
None declared.
Professor Adrian Esterman is Chair of Biostatistics at the University of South Australia

The decision on whether to roll out the AstraZeneca vaccine to the majority of the Australian population is not an easy one. Based on interim results, it has 62% efficacy against symptomatic disease, compared to the over 90% for the Pfizer-BioNtech vaccine. If after the full Phase 3 trial results are in, the AstraZeneca efficacy remains close to 60%, then it would not be possible to achieve herd immunity using this vaccine.

In other countries where the epidemic is rampant, an efficacy of 60% would still be very helpful in dampening down transmission and providing relief to the hospital services. However, Australia is luckily not in that position, and there is a strong argument for vaccinating as soon as possible the at-risk population with two doses of the Pfizer-BioNtech vaccine, and holding off for the rest of the population until more doses of it are available.

However, at this stage, we do not know the final Phase 3 results, and the AstraZeneca vaccine might have much higher efficacy than reported in the interim results. We also have the Novovax vaccine available in a few months, which might also have better efficacy. Many members of the general public are concerned about the reported low efficacy of the Astra-Zeneca vaccine. I think the government needs to be flexible in its rollout decisions once we have a better understanding of the efficacy of the other vaccines.

Last updated: 13 Jan 2021 11:12am
Declared conflicts of interest:
None declared.

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