EXPERT REACTION: Aussies likely to start COVID-19 vaccinations in March after UK approves Pfizer-BioNTech vaccine

Yesterday was a significant day in the global fight against the pandemic as the UK became the first country to authorise the Pfizer-BioNTech COVID-19 vaccine for emergency supply on the recommendation of its independent Medicines & Healthcare Products Regulatory Agency. 
 
The Australian Government secured a supply deal for 10 million doses of the Pfizer-BioNTech vaccine in November, with the first doses expected to arrive in Australia early next year pending regulatory approval by the Therapeutic Goods Administration.  
 
Emergency authorisation was granted by the UK regulator, an independent body which based its recommendation on analysis of the initial preclinical trials through to the phased human clinical trials. The results of Pfizer-BioNTech's phase III clinical trials are expected to be published in a peer-reviewed scientific journal in the coming months.  
 
From a public health perspective, we hope to see as many vaccines as possible reach this stage and to pass regulatory approvals should they prove to be safe and effective. Not all vaccines have the same level of efficacy across different demographics or are easily transportable, so it is important to have options that work across the broader population.  
 
As we wait for a vaccine to be rolled out in Australia, we must remain vigilant and continue with contact tracing, social distancing and practising good hand hygiene.

While this is good news, it is important to remember the fight against COVID-19 is far from over. Current vaccines confer protection against the COVID-19 disease, but immunised individuals who are subsequently exposed to the virus may still become infected and, though they may not show symptoms, might remain infectious for a short time. We all therefore need to continue to follow public health measures to limit to spread of the virus, even when a vaccine is deployed here in Australia.  
 
The Pfizer-BioNTech vaccine is quite novel and works by inserting the genetic code for the spike protein of SARS-CoV-2 into the cytoplasm of the cell – if you imagine the cell as a fried egg, it’s the white bit. The cell then produces the spike protein using this code, which our immune system recognises as foreign and we develop immunity, which then protects us, should we subsequently become infected by the real virus.
 
The genetic code in the vaccine is in a form called “messenger RNA” or mRNA.  This is different to the DNA in our cells. which is found in the nucleus – the yellow bit of the fried egg model. The mRNA in the vaccine does not enter the nucleus and cannot incorporate itself into our genes – it only lasts for a few hours, while being used to make the spike protein and is then destroyed by our cells.
 
Pfizer and BioNTech’s primary efficacy analysis of the vaccine has shown it is 95 per cent effective against COVID-19. This is a very encouraging level of efficacy, considering most seasonal flu vaccines are around 60-70 per cent efficacious.  
 
However, this particular vaccine needs to be stored at around -70°C and the logistics of maintaining this temperature through supply chains is a significant hurdle to overcome, before a widespread rollout of the vaccine can be implemented.

The emergency approval of the Pfizer/BioNTech COVID-19 vaccine by the United Kingdom (UK) regulator, Medicines and Healthcare products regulatory Agency (MHRA) is not surprising. The number of individuals in the UK becoming infected with SARS-CoV-2 continues to rise along with fatalities. 

Based on currently available information, the MHRA have determined the vaccine meets required standards of safety, quality and effectiveness. 

Approval will also have been based on careful consideration of the risk versus the benefit of use. The risk of developing an unforeseen serious adverse reaction to the vaccine being low compared to the greater risk of contracting the virus (i.e. benefit of vaccination is greater).

The UK is also comparatively smaller in size to Australia and uses a catchment system to determine where citizens should seek medical treatment. 

Consequently, the logistics of large-scale vaccination by the National Health Service (NHS) will not be as complex as the vaccination process for Australia.

Australian Health Minister Greg Hunt has confirmed the Australian Government is on track to start COVID-19 vaccinations by March 2021. 

The urgency for vaccination in Australia is lower as viral transmission and fatalities from SARS-CoV-2 are significantly less to those experienced in the UK. 

Australia is also in a unique position to observe and learn from the UK vaccination experience and, if necessary, adjust for unforeseen problems in vaccine distribution, storage and clinical effects before this process begins here.

The latest announcement from Minister Hunt is a significant step in vaccinating against SARS-CoV-2. It is a truly inspiring effort of medical science to develop and produce a vaccine within ~10 months after the SARS-CoV-2 virus was first described. To now see it being rolled at a global population level is truly remarkable.

 

We have seen a steady stream of positive news relating to vaccines in recent weeks, particularly relating to efficacy results from phase 3 trials from a number of candidates.

To see this now progress to a regulatory approval is another key milestone, hence is truly exciting news.

While the press releases in recent time have reported results that suggested a regulatory approval would be attained, the fact that this has now happened indicates that the full dataset that would have been thoroughly reviewed for this to happen must have indeed demonstrated the required efficacy as well as safety of this vaccine.

A regulatory approval from the UK does not mean the vaccine will automatically be approved in Australia, it will still be subject to our own appropriately rigorous approval process. However, it obviously makes it likely that it will be successful. This means that the target of having a vaccine available for use in Australia early next year is another step closer.

The approval for emergency use of the Pfizer COVID-19 vaccine in the UK comes at a time when the UK is in the grip of a severe second wave of SARS-CoV-2 infections. Over 13,000 new cases and more than 600 new deaths associated with COVID-19 were reported in the UK yesterday.

The UK has initially ordered enough doses of the vaccine to vaccinate just under a third of its population, with immunisations expected to commence directly.

At this point, Australia is in a much better position in terms of number of cases and community transmission than the UK. Currently, Australia can afford to wait for full approval for use of the vaccine from the Therapeutic Goods Administration rather than initiate a request for emergency use. Vaccination in Australia is forecast to begin in March 2021.

The beginning of vaccine rollout in the UK is an astounding achievement considering the virus was unknown less than a year ago and vaccine development typically takes 10-15 years. Vaccine rollout will, however, be a drawn-out process and current measures to limit spread of the virus must continue to be adhered to throughout.

Just a few weeks ago, we were not sure whether it was possible to get an effective and safe vaccine against COVID-19. The emergency use authorisation of the Pfizer-BioNTech mRNA-based vaccine by the MRHA (the UK’s equivalent to the TGA) is therefore fantastic and welcome news.  

The MRHA [UK Medicines and Healthcare products Regulatory Agency] has concluded that the vaccine has met its strict standards of “safety, quality and effectiveness”. However, the emergency use designation also means that the MRHA has not yet fully analyzed the Phase 3 trial results.

The Australian government has pre-purchased 10 million doses of the vaccine, and it is likely that the TGA will wait to give full approval rather than taking the same emergency use path as the UK.

This is because epidemic situation in the UK is dire, whereas we have very few active cases in Australia.  The rollout in Australia is therefore unlikely to occur until March, giving the TGA more time to fully examine the Pfizer trial results. There are still question marks about the vaccine. These include how well the vaccine will work to prevent infection (rather than prevent symptomatic disease) and how long.

This is really encouraging and exciting news and I suspect will be followed by similar announcements from both the US and European regulators in the next few weeks regarding the Pfizer vaccine. 

In addition the Moderna and Oxford vaccines will be also be going through regulatory approval. Once rolled out, itself a massive challenge, we need to simultaneously launch robust safety systems to detect any serious adverse reaction that was not picked up in the trials. 

Some key questions will need to be answered in the next year including - how long does immunity last and are booster doses required? How effective is the vaccine in specific groups – such as pregnant women, elderly people with chronic diseases, and immunosuppressed people. 

How does the vaccine perform when co-administered with other vaccines, especially the flu vaccine. These are just some of the questions we need to answer in the coming months.

This is very good news. A vaccine, with high vaccination rates in the whole population, is the only exit strategy for the pandemic. All the misinformed talk of elimination does not consider that the technical definition of elimination requires high immunity which can only be achieved by mass vaccination.  

With a vaccine that is 90 per cent effective, we would need 80 per cent of all Australians vaccinated at a minimum to achieve herd immunity and stop community transmission. This should be the public health goal and all efforts should be made to achieve this, as this is our best bet for economic and social recovery.  

So, we need to be working now with people who may be hesitant about vaccination, and making sure we can reach a target of at least 80 per cent of Australians vaccinated. I don’t think it is a good idea to just make it available and hope for the best - there must be a plan on how to get 80 per cent of people vaccinated. The logistic and programmatic side of this task should not be underestimated.

Whilst we do have the experience of the 2009 pandemic, the vaccine arrived after the epidemic peak, and it is estimated 21 per cent of people >18 years were vaccinated by 2010.  

This is a much greater task - in our routine National Immunisation Program we vaccinate 4-5 million people a year. This needs to increase to up to 25 million.  And if it happens in a slow trickle, we will be living with COVID for longer. The best impact will be to achieve high vaccination rates within one to two months.  Of course, this can only occur when there is adequate supply. Until then we have to have clear guidelines on priority groups, such as health workers, who have three times the risk of COVID-19, and aged care workers. A limited initial supply should be given to priority groups. 
 
This is the first time since eradication of smallpox that mass vaccination (meaning of the whole population) may occur in any country. There are many considerations for this - do we expect GPs to vaccinate everyone? Will pharmacists be allowed to vaccinate - they vaccinate for flu, but that is a tried and tested, old vaccine. Should we be scaling up the training of nurse vaccinators? Will there be public vaccination clinics? Maybe the drive through testing sites can be expanded to vaccination clinics.

We also need to ensure proper cold-chain infrastructure - some of the vaccines need to be kept at very low temperatures. Any break in the cold chain can render a vaccine ineffective. We also need improved vaccine safety monitoring as these are brand new vaccines, and sometimes rare side effects only become apparent post-licensure, because clinical trials may not be powered to detect very rare side effects.