COVID-19 vaccination in Australia

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Welcome to the Australian Prescriber podcast. I'm David Liew, one of the founding co-hosts of the podcast and the voice you hear at the beginning of each episode. Ever since our podcast started out exploring the great material that Australian Prescriber the journal covers nearly four years ago, we've been delighted by your response. And 100 episodes later, yes, this is our 100th episode, my co-hosts and the editorial team at Australian Prescriber continue to enjoy every single minute of it. Thank you to all the article authors who have made the effort to be interviewed by us to explore their thoughts on the podcast and thank you for all of you for tuning in. We really couldn't do it without you.

And today, dear listeners, we have a great episode ahead of us to celebrate 100 episodes. In these pandemic times, it seems normal for one issue to completely dominate discussion in our society. It's really no surprise that all anyone's talking about is the COVID-19 vaccine. COVID vaccination has been highly anticipated as a white knight in saving society as we know it, but how did we get here and how can we navigate the challenges ahead? I'm David Liew, your host for today. And I welcome back just the person to answer these questions, Professor Kristine Macartney who is the Director of the National Centre for Immunisation Research and Surveillance and an infectious diseases physician at the children's hospital at Westmead in Sydney. She's written with her coauthors about COVID-19 vaccines in the February 2021 edition of Australian Prescriber and will be updating this on the podcast today. So it's a pleasure to have her on. Kristine, welcome back to the program.

Thank you very much, David. It's a pleasure to join you again.

So Kristine, when you and I spoke about zoster vaccines on the podcast this time last year, we were talking in a very different world and an enormous amount has happened. There's incredible scrutiny in this space now in every minutia. What's it been like working at this time, in this kind of environment, in this space?

Look, it's been an incredible year for everyone, hasn't it? I've been fascinated by our response collectively as humankind to this most terrible pathogen. I suppose going back to the very earliest days, I knew it was going to be a vaccine-preventable disease. I think within a very short time, it was apparent that this virus had the capacity to cause the sort of destruction of lives and livelihoods that we've seen unfold. And it was quite apparent early on that we were going to move to quickly develop vaccines. And I suppose I'm a vaccine nerd of longstanding time now. As a paediatric infectious disease specialist, actually before I even specialised in infectious diseases, I was seeing the powers of vaccines in preventing things like epiglottitis and meningitis from Haemophilus influenzae. I mean, the fact that I knew hardly anyone who'd had polio I thought was absolutely incredible. I looked after a lot of children in the early ’90s with measles.

So probably I've always thought that vaccines should be the centre of our world because, as we all know, an ounce of prevention is worth a pound of cure. And it is quite incredible now to see vaccines becoming so central to everybody's dialogue. And to really, I think simultaneously understand that the public have come on board and are interested in the science behind all of this so much. I think this is something to really celebrate actually. And I know that we're going to manage this disease through vaccination. Immunisation represents our ticket out of the pandemic with a lot of caveats around how we can do that. It's not just about making the vaccines, but it's about using them. I'm excited to see what this year brings, 2021, for Australia and for the rest of the globe.

Well, I'm really glad that vaccine nerds like yourself are the heroes here. Vaccines have always been one of the great medical miracles really. I think there's been enormous fascination from the public though as to how this has happened in such a quick period of time. I mean, how fast do you think this really has been? Is it something that's been actually years in the making building up to this, or have we been leveraging off concentrated efforts, or has this really been that kind of modern miracle?

Do you know it's been all of those things, David. So when I think about it, the time to sequence the virus... and we actually know that that sequence of the virus was posted first here by University of Sydney researcher Eddie Holmes, he was the first to post that sequence. Then to the growing of the virus at the lab at the Doherty, then to being able to make mRNA and the genetic code for the virus that is formed, or for the spike protein in particular that has formed the basis of some of the earliest vaccines that went into clinical trials, the mRNA vaccines. That didn't actually just come by chance. That came because we're in the midst of a massive global scientific revolution. And in fact, vaccines like mRNA vaccines have been in the making for decades. New technologies, what we call designer vaccinology has been growing at a record pace in the last decade.

We've seen organisations like the Coalition for Epidemic Preparedness and Innovation, which is actually all about making a vaccine for disease X, a virus of epidemic potential. We saw that organisation start in 2017. So in many ways, viruses that have popped up and been awful in the last two decades, like SARS of course, another coronavirus, like MERS, a second, very serious coronavirus, like Zika virus, like Ebola, which in fact has been controlled through the use of a viral vector vaccine not dissimilar to the Oxford-AstraZeneca vaccine that we'll all shortly be having in Australia, all of this has been preparing us for this grand pandemic. And that has allowed the vaccine scientists, the vaccine developers, and those who have been looking now to actually turn vaccines into vaccination. So remember it's vaccination that saves lives, not the vaccine sitting in the vial, as remarkable as it might be. All of that scientific endeavour has been underpinned actually by decades of work.

So I think people should be reassured about the fact that the technology, the scrutiny, the regulatory rigour, we've been decades in making this possible. And of course everything's happened at pandemic speed, but the public can be reassured that that's underpinned by all of this science. And that really, as you've said, the whole world's turned their mind to COVID. All of the brightest minds have been thinking about how to ship these vaccines, how to test these vaccines. The best statisticians have been looking at how to make sure there's nothing hidden or bad in the data. Every part of the world has worked together to make these vaccines come to bear. We've still got a lot of work to do, a huge amount of work in front of us, to deliver them. But the safety is there, the efficacy and effectiveness is there. And I hope that every pharmacist, doctor listening to this today, every nurse immuniser can be confident about that as they encourage people to take up these vaccines.

I mean, that's such a great message. And I think that all of that subtlety sometimes gets lost in the discussion. I hear a lot of people talk about, well, usually a vaccine takes 10 years to come through development, and this has happened so quickly. Do you think that downplaying all the effort that's come up to this point actually undermines the public confidence in the safety of the COVID vaccines that we have?

I think people should realise a few things, that the processes have been incredibly rigorous. The ability to study these vaccines has been possible, it's been possible to do very quickly because we've had a virus that's just been completely out of control. So when people were planning the trials, we didn't realise there were going to be so many cases. It's been absolutely devastating. We've had, in the United States alone, more than 500,000 [corrected 2022 Mar 1] people have died from this virus, an inconceivable figure. Now the only possible silver lining that you could make out of that is that actually, where the trials have gone on, there's been so many cases of COVID that we've been able to have tens of thousands of people involved in the trials that have given us so much data about the safety and effectiveness that people should be very encouraged.

There is actually more information on these vaccines than we've had for other vaccines that we've licensed in the past. And that's in terms of the tens of thousands, as I mentioned, people who've been studied for safety and for outcomes over many months after the vaccines. These vaccines give you a sore arm and can make you feel a little flu-like after, in the day after vaccination. You can have a headache, a bit of a temperature, some muscle aches, and even some chills in that first 36 hours or so. But that's temporary, not terribly severe, and goes away. And that's our immune system working in response to the vaccines, developing a natural protection that is going to help us not get sick from COVID-19 and not spread it to others.

We have been very encouraged by the enormous volume of data on safety that exists. There's no long-term safety concerns that have been seen. There's no long duration of symptoms that have been seen in particular people. Now, I think we've had over 200 million doses of the vaccine given to people around the world. Australia's program's starting a little bit later than other parts of the world, which we haven't had COVID-19, I think that's actually been fitting that the vaccines have gone to where they've been needed the most. But it's enabled us in Australia to also reap the benefits of understanding what the program looks like in other countries, seeing that all of these millions of people have been vaccinated, there haven't been any serious safety signals. And even more so, that the vaccines are showing their effect now in populations around the world. In Israel, in the UK, there are now very clear studies indicating the effectiveness of vaccines in preventing people from being hospitalised, in keeping them out of the intensive care unit. And of course that'll be preventing people from dying and lives being disrupted.

I mean, what an incredible time to see that in action. Just so that we've said it and we can put it out there, I think people want to know, has this been regulated in the same way in Australia? Have we done this in any other different way to how a normal vaccine would be approved?

Actually, I think we've done it with an even higher level of scrutiny, David. So we've given these vaccines what's called provisional registration here in Australia. And at this stage, that is both for the Pfizer vaccine, which is called Comirnaty, and the AstraZeneca vaccine, Oxford-AstraZeneca vaccine. Now in the UK and in the United States, they authorised these vaccines... well, certainly they've authorised Pfizer only in the US at this stage, they haven't yet licensed AstraZeneca, but they authorised these using what's called an emergency authorisation or an emergency use authorisation. And that gave them a lot of sort of permissibility to say we're in an uncontrolled pandemic, we're going to use these vaccines. Australia took a little bit longer to get the vaccines registered because we said let's look at even more data. We're not in that incredibly urgent space, and we can do what's called a provisional registration.

So in fact, we've had more tranches of data come through than what were available in the first instance to the other regulators. But it's only confirmed what we already knew, that there's safety, there's efficacy, and these vaccines are suitable to use. Do we need to track the vaccines and monitor how they continue to perform? Absolutely yes, there is no doubt about that. But the other thing I've been buoyed about and encouraged about in this pandemic is the incredible global cooperation between regulatory agencies. And I would shout out to the efforts here of our Therapeutic Goods Administration. They are a world-class regulator. They've been leading, with the International Coalition of Regulatory Agencies, a number of modules, and they've been up 24/7 engaging with other regulators from across the world to be sharing information, to be learning and that's helped us all a lot.

Well, I mean, I'm very happy as a clinical pharmacologist to hear about the pharmaceutical regulators being the heroes every now and then as well.

Well, look, I think there are always things that we can do a little bit better, but I know that the level of cooperation that's been brought to bear has been outstanding.

Can you give us a really straightforward way of trying to understand how does an mRNA vaccine work or how does a viral vector vaccine work, to explain to our patients?

Sure. Look, I think these are a new class of vaccine. So they work in a slightly different way to vaccines that people might be used to. And possibly people have thought, well, a vaccine is either a weakened or a killed form of the virus or the bacteria. And there are COVID-19 vaccines that have been developed by inactivating the whole virus, they're mainly the Chinese vaccines. There are other vaccines that are being developed that make just that spike protein part of the virus, and then that's what's given via the injection along with a substance called an adjuvant which helps prime and boost the immune system, and that's the Novavax vaccine that we think is showing good efficacy data and may well be registered within a few months.

The genetic code vaccines are a little newer and I understand that people want to get their head around that, but they both involve a very simple strategy of injecting either that mRNA or that DNA in a way that it can get into the cell. The cell can just actually read that tiny little snippet. And all that code does is teach our cellular machinery, our cells in that injection site area, to make the spike protein. And they just make this protein. It's just a very simple protein, relatively speaking. And it doesn't mean that our whole body's making the spike protein, it just means that those cells at the injection site make the spike protein. But because they're our own cells making the spike protein and it's our own immune system from the very beginning reading this, we have this incredibly strong immune response to what is a tiny amount of protein and a tiny injection, relatively speaking.

Then the mRNA goes or the DNA that came through the viral vector vaccine, it goes, it gets degraded. And it's only there as a short, instant message to tell our bodies to turn on our immune system to this foreign protein. And then our antibody memory kicks in. So from there on it's all natural, it's our own body saying, "We recognise we saw a snapshot or a Snapchat, even, of a foreign protein. We're going to make these antibodies." We're going to kick off the training session for our immune system to be able to then know, aha, I've done this before. I can respond to this guy if he comes along and I meet him again. And then those immune memory cells, both the T cells and the B cells, they've got it. They get a second go because they see another dose with dose two down the track, and then they're saying, "We know this guy. We can pump out antibody. We can turn on our innate and cellular immune responses if we meet this virus again and stop this body getting sick."

I like to think of immunisation as actually being quite natural. And I know that not everybody feels that way, but remember that our immune system is doing this all the time for other pathogens or for other proteins and substances that it might meet that are being immunogenic. We meet an E. coli when we eat a hamburger and our body says, ‘No, I'm going to have a little bit of an antibody response to that E. coli.’ We're not conscious of that, but when we have a vaccine, we're also just using our immune system in a very productive way, rather than having to turn it on because we're overwhelmed by a horrendous virus that we can't block.

I mean, it sounds like this technology as well has enormous potential for adaptability. Do you think that there's a possibility this type of technology is adaptable to say other strains of COVID as they emerge or potentially even other coronaviruses in the future?

Look, absolutely. We're going to see a whole new way of approaching the prevention of infectious diseases here because the mRNA vaccines, whilst they held a lot of promise, there just hadn't been the push to get them developed for some of the pathogens. I don't know, nothing ever sort of gelled to bring them together in a way that we've seen now. And whilst there are some issues still in terms of the cold chain requirements, in terms of both Moderna and Pfizer, for example, needing to be either frozen or ultra frozen, once we can get over some of those technical challenges, these are vaccines that are probably, we're going to see a lot more of in the future.

And I think that right now, we don't have any other coronaviruses that are causing severe disease other than of course MERS which does cause sporadic outbreaks. And this will probably stimulate the production of a MERS vaccine to be utilised in those particular settings. But it'll allow us to potentially develop vaccines much more quickly should we have other viruses emerge and cause havoc, either locally or globally, like the coronavirus has this time. So I think it will definitely change the face of vaccinology. And in fact, we've already been seeing this. So we've already been seeing the way, in cancer chemotherapy, for example, to use the immune system to help us fight cancer. So this is probably going to underpin decades of breakthroughs in science and health more generally.

Right. So well given that, perhaps maybe you can tell me a little bit about the process for postmarketing surveillance, for pharmacovigilance regarding this. I mean, everything is rolling out very quickly. What kind of processes exist in Australia to be able to capture this? And can we draw on overseas data as well?

So in Australia, we've made a lot of steps forward in pharmacovigilance or monitoring of both medicines and vaccines, and particularly in the vaccine space. About a decade ago, we had the episode with one of our influenza vaccines where it very unexpectedly caused high rates of fever and indeed some febrile seizures in young children. And since that time, a lot of effort has been put into strengthening the reporting of adverse events following vaccination. And we also have a new active vaccine safety surveillance system which is being rolled out every year to hundreds of thousands of people. It's called AusVaxSafety, it's fed by two wonderful automated systems, SmartVax and Vaxtracker, that can link up to routine practice management software and clinics. And that allows real-time tracking of vaccine safety in the community in Australia, as well as the usual reporting.

So we've done a lot with vaccine safety. There's also a network of outstanding clinicians who can talk with patients and indeed their general practitioners or pharmacists if there are any concerns around safety and follow them up if they might have any unusual side effects from vaccination. We need to do a little bit more in terms of linking some of our very comprehensive, large databases to ensure that we can look into safety signals, should they occur, but that's underway with the pandemic as well. And I think we're extraordinarily well placed. In fact, from an international perspective, we're quite highly respected for what we do in vaccine safety across the board. And that very same SMS monitoring active surveillance system that I talked about, a copy of that had actually been stood up in the United States. They've made a system called V-safe which is using SMS surveys to inquire about how patients felt after vaccination in the United States. I know they looked at our system here in Australia.

But talking about the international safety monitoring, as I mentioned, there have been over 200 million vaccine doses given already. And I'm very privileged to be a member of the WHO Global Advisory Committee on Vaccine Safety. We have mechanism to review all of the safety signals that are coming through. And I'm delighted to tell you that there just aren't that many. So with hundreds of millions of vaccines having been delivered, the safety profile has really so far stood up to what we've seen in clinical trials. A sore arm for a day or two, a little bit of tenderness in that muscle where the vaccine was given, not much redness or swelling, fever in a proportion of patients up to around a third or a half, but usually low-grade fever, sometimes with muscle aches, headache, and sometimes chills for the first day or two. But those symptoms settle right down quite quickly. And there are no long-term or other serious safety signals that have come through.

The only exception would be anaphylaxis. And we know that this immediate, serious allergic reaction is something that can happen with any vaccine. The rate at which anaphylaxis occurs following a COVID-19 vaccine initially appeared slightly higher than we might see for other vaccines, but actually that's settled down. So now it's around perhaps three or four cases of anaphylaxis per 1 million doses of vaccine given. So that's around one person in every one or 200,000, and that's why we have adrenaline on hand, that's why we ask patients to stay and be observed for 15 minutes after vaccination.

Absolutely. Kristine Macartney, thank you very much for joining us today.

Thank you very much, David. It's a pleasure to join you again.

The views of the guests and the hosts on this podcast are their own and may not represent Australian Prescriber or NPS MedicineWise. Thanks for joining us once again, stay safe, and we look forward to seeing you next time.