• 21 Nov 2023
  • 16 min 50
  • 21 Nov 2023
  • 16 min 50

David Liew talks to Ketaki Sharma, a staff specialist at the National Centre for Immunisation Research and Surveillance, about the latest developments in COVID-19 vaccines and what the future of vaccination looks like in Australia—who needs boosters and which vaccine should they have? Read the full article by Ketaki and her co-author, Jean Li-Kim-Moy, in Australian Prescriber.

This interview was conducted on 21 October 2023.


These vaccines are really well tolerated by children. Compared to other vaccines, they don't seem to be particularly likely to cause fever or lots of other uncomfortable symptoms.

[Music] Welcome to the Australian Prescriber Podcast. Australian Prescriber, independent, peer-reviewed and free.

We've heard a lot about COVID-19 vaccination early in the pandemic and, in fact, that is what has given us a pathway to resuming the function of our society. COVID-19 is an ongoing issue, however, a constantly evolving one, and vaccines are on the front line of managing it. So here in 2023, what do we do about COVID-19 vaccines in our everyday lives, and what does the future look like? Ketaki Sharma is a staff specialist at the NCIRS, the National Centre for Immunisation Research and Surveillance, and she's co-authored an article in Australian Prescriber about COVID-19 vaccines in 2023, and she joins us on the podcast today. Ket, welcome to the program.

Thanks, David. Thank you for having me.

So tell me a little bit about how COVID-19 evolving has affected vaccination and, potentially, does it affect at all the rationale for vaccination?

Yeah, it absolutely does. So COVID-19 has evolved starting from quite early in the pandemic with the emergence of different variants. I'm sure the listeners would be familiar with the nomenclature used for those variants. We started off with Alpha, Beta, then we had a very big wave of Delta. That one was particularly virulent and certainly had an impact on the push for vaccination because we were seeing much more severe disease. More recently, all of those older variants have been replaced by Omicron. So since the emergence and global domination of Omicron during 2022, we no longer detect any of those older variants.

As we all know, the original vaccines were based on what we call the ancestral or the original version of SARS-CoV-2, sometimes also called the Wuhan strain because that's where it emerged. We are now facing a virus that's adapted with several different rounds of mutations. There is evidence that when you look at the neutralising antibody or the immune responses to that original vaccine compared to some of the newer vaccines based on variants, there is a benefit to having a vaccine that is based on a more recent variant of SARS-CoV-2. So it has, and it probably will continue to influence COVID-19 vaccine development just like we see with the annual flu vaccine, which is tailored every year to target the most recent strain.

So perhaps I can ask you: COVID-19 vaccination now, what's the primary aim of what we're trying to do in terms for our patients and for society? It sounds like things have probably shifted from that time at the very beginning.

Yeah, absolutely. So the initial stated aim of the Australian COVID-19 vaccine program was to reduce infection and even potentially reduce transmission of the virus. But now we are well past that, and the main goal is to reduce the risk of severe illness specifically. That's why in the most recent rounds of booster advice, the people that are targeted are really those who still are at risk of severe illness, namely older adults and people with risk factors like medical conditions that increase their risk of severe COVID.

Right. So perhaps maybe we can run through the booster recommendation first. Obviously, the vast majority of Australians have had primary vaccination. Talk me through the booster recommendations now.

The two key groups that should be vaccinated now would be people aged 75 years or older if they haven't had a dose in the last 6 months. You can consider vaccination for people aged 65 to 74, that includes healthy 65- to 74-year-olds. You can also consider vaccination for people aged 18 to 64 with severe immunocompromise. There was also an earlier statement issued by ATAGI [Australian Technical Advisory Group on Immunisation] in February of 2023 that was a little bit broader. So that advised to consider vaccination for adults aged 18 to 64 even if they have no risk factors and for 5- to 17-year-olds who do have medical risk factors. So if people hadn't even had that first dose and so they're still well over 6 months since their last dose, you could also consider catching them up as well. I know all of this is extremely complicated and hard to take in when you're listening, so I would encourage listeners to have a look at the COVID-19 chapter of the Australian Immunisation Handbook, which has recently been published and which summarises all of this information in a more digestible way.

For that considered category, what would make individuals decide to have that vaccine or not?

So obviously the most important thing, I think, is the individual's preferences. So some people are quite concerned and they want regular booster doses of COVID-19 vaccines even if they're not in one of those risk groups. So sometimes we find ourselves having to reassure people the other way that in fact, actually, if you are a young healthy person you don't need another dose right now. So personal preference is one of the most important ones.

Other things to consider are if they have had previous COVID-19 infections, which we think the vast majority of Australians have had. So recent serosurveys have showed over two-thirds of adults have evidence of past infection, but if they don't think they've ever had COVID, then they wouldn't have hybrid immunity. So that's another reason you might want to give a relatively younger adult a booster. The other thing is life circumstances. So for example, if somebody's about to go on a holiday and they really don't want to get COVID, impending overseas travel or a new job working in a health facility where they anticipate they might have increased risk, that just might influence the specific timing of giving someone a booster dose.

As someone who's had COVID overseas, it wasn't a lot of fun, so I can certainly understand the rationale behind that. Can we just talk a little bit through hybrid immunity, because I think people wonder about that a lot?

So hybrid immunity is clearly better than having protection from just vaccination alone or from just infection alone. In Australia, we think the majority of the population probably already has this hybrid immunity, but both of those types of protection wane over time. On top of that, we will potentially keep facing new variants of SARS-CoV-2. So one of the more recent ones called BA.2.86 has some mutations that may make the vaccines or past infections a little bit less protective. That doesn't necessarily mean it'll cause severe disease—it just means that hybrid immunity will not necessarily provide very long-term protection against severe disease for all members of the population. So we have to keep on monitoring the evidence to see which groups are emerging as being at continued risk.

Now in terms of which vaccine to go with. You've put a link in there to a beautiful A3 poster. How would we go about approaching what type of vaccine to give people in this booster setting?

I think now we're sort of entering a situation where it almost shouldn't matter. Just like the annual flu vaccine, the vast majority of people don't turn up to their GP or pharmacist asking for a specific brand of flu vaccine. They just ask for that year's flu vaccine. So that's been the case with the variant-based vaccines we've had so far. So we've had two different BA.1-based vaccines. We've had two different BA.4-5-based vaccines, and all of those are based on subvariants of Omicron. ATAGI's advice has been to consider them all basically equivalent, even if BA.4-5 was a little bit later than BA.1, they appear to be equally immunogenic against the circulating variants at the time that they were used. We now also have from the TGA [Therapeutic Goods Administration] the approval of two newer vaccines based on XBB.1.5, which is another Omicron subvariant that's even more recent.

So we currently know that those vaccines are very immunogenic against the newer Omicron subvariants, including BA.2.86. We don't yet have clinical data to show if they're very superior in their protection against severe disease. So the possibilities are if they turn out to be very superior, then potentially there could be a preferential recommendation. But it seems equally likely that people would be recommended to just have the latest vaccine that's available, not consider which brand, not consider the specific doses, just get your COVID-19 vaccine.

That simplicity in a sea of choice is definitely something that's appreciated for us as frontline clinicians. I think the other little bit of complexity is about what to do about primary vaccination. There might be some adults who haven't been vaccinated who might be still keen to get vaccinated, but there's obviously a large number of children who have never been vaccinated. What are our current primary vaccination recommendations?

So ATAGI's current recommendations are that all children aged 5 and older should have a primary course of 2 doses of COVID-19 vaccine. For children under the age of 5, so 6 months up to 5 years old, you're only recommended to have a primary course if you have risk conditions for severe COVID-19. So it's quite a limited vaccination program for those very young children, but recommended for all children 5 and older. But I will mention that other countries around the world, some of them have stopped vaccinating healthy young children or reduced down to a single dose. So that's potentially something that we could see around the world becoming more common. I think part of the reason for that is widespread exposure to past infections of SARS-CoV-2. Even at the very beginning before anyone was exposed, the risk of severe COVID-19 was always extremely low in young children.

So let's get the flip side of this, and I think some of the concerns that maybe some people had about vaccinating in younger children and adolescents was about vaccine safety. If the accusation before was that we hadn't had enough experience, certainly we've had a lot of experience with vaccine safety now.

Yeah, absolutely. Over 13 billion doses of COVID-19 vaccines have been administered globally. So we definitely have a lot of safety data, probably more safety data on these vaccines than any other product in history. In Australia specifically, there is data available on COVID-19 vaccine safety in children, which you can link to from the NCIRS website through a program called AusVaxSafety. It looks at the reactions reported by children in the days following vaccination, and what you'll find is that these vaccines are really well tolerated by children. Compared to other vaccines, they don't seem to be particularly likely to cause fever or lots of other uncomfortable symptoms. The other safety concern that has been raised in relation to young people is myocarditis, so inflammation of the heart muscle, and also pericarditis, which is the heart lining, but that tends to be more common in older adults.

Myocarditis, the highest risk is in young adolescents or young adults —16, 17 would be the peak age, and seems to be most common after the second dose, but still overall rare. And it's important to recognise that the risk of myocarditis is much higher with the virus itself. So based on that risk–benefit analysis, vaccination was still recommended. As I've mentioned, it doesn't seem to be something that young children seem to be at risk of.

So I know I'm getting really into the minutiae here, but if someone does have an adverse event, what should their clinicians do then? Should they be reporting that adverse event, and what about revaccination after that?

Yeah, so we would encourage clinicians to report any adverse events that you think are either severe or unusual. So you don't need to report somebody coming forward with a fever or a local injection-site reaction that you think is within the expected norm following vaccination. But certainly severe adverse events, we would request all immunisation providers to report those to the TGA. Then in terms of assessment and management of the adverse event, as with all other vaccines, it depends on the severity.

So the only absolute contraindications to future doses of COVID-19 vaccines would be anaphylaxis or a very severe adverse event that has been attributed to a previous dose of that vaccine. The only other contraindication is the very unique one, which is a previous history of capillary leak syndrome, which is specifically a contraindication to the Moderna vaccine. But that's so rare, it almost feels strange to mention. The main thing to recall is anaphylaxis doesn't seem to be any more common with COVID-19 vaccines compared to any other type of vaccine, and the vast majority of people tolerate these vaccines really well.

So let's look forward a little bit in terms of what the future might hold, always a slightly dangerous thing within COVID-19. So how might the future variant landscape evolve? How do you think we'll work with vaccines to try and combat those evolutions?

So there's actually already a committee established whose entire remit is this question, and it's a technical advisory group to the WHO specifically on COVID-19 vaccine composition. So what that committee is doing is monitoring the virus and variants as they evolve and issues guidance. So in May of 2023, that committee recommended development of vaccines based on the XBB.1.5 subvariant, which is exactly what we've seen. So I think in future we can see similar coordinated efforts to recommend which variants appear to be either particularly virulent or particularly dominant, and that can inform future vaccine development.

There are also vaccine developers looking at broader vaccines, so using components from different types of coronaviruses and not just focused on one particular variant. So theoretically, those could provide broader protection. There's also vaccines being looked at and even registered in a couple of countries overseas with a different platform like intranasal vaccines. That again, could theoretically broaden your immune response because it engages the innate immune system and different parts of your immune system. So there is a potential that we may see better vaccines come out in the future but, at the very least, I think we can expect to see periodically updated vaccines to match what the most dominant variants are.

Finally, I think a question which often gets asked: what about timing with the influenza vaccine? That's obviously another vaccine that we give seasonally and may well be nice to align with the COVID-19 vaccination program. Do you think that's something that we're likely to see in the future?

Yeah, absolutely. In fact, that's another product that is being developed by multiple manufacturers. So combined COVID-19 and influenza vaccines. We are not yet sure what the exact seasonality of SARS-CoV-2 is. In Australia, we have had peaks over summer months as well, but we certainly have also seen severe illness rise over winter months. The last ATAGI guidance for booster doses was issued in September, so it does make sense that, 6 months later if you have patients that are still at high risk, it may well be very convenient. By that time, I expect we may have updated advice in the Handbook, but it may well make sense to combine those two vaccines. One of the biggest benefits of that is the logistics for providers not having to bring people back multiple times and also being able to be opportunistic. Because if someone's coming in for the flu vaccine and they haven't been thinking about COVID, you can look at their risk factors and you can get them vaccinated while they're there.

Great. Well, we thank you and everyone at the NCIRS for all their hard work in trying to make sure that we keep up with this evolving landscape. Thank you for your work on this article in Australian Prescriber. Please do go and check it out, and thank you very much for joining us on the podcast today.

Thanks for having me, David. Before I go, can I just plug the NCIRS website where we're soon going to have an updated decision aid for COVID-19 vaccines. So that's something that your patients will be able to click through themselves and think about all of those factors that we've discussed and think about whether they might be ready to have another booster dose.

Brilliant, that sounds incredibly useful, and thank you very much for joining us.


Ketaki Sharma is a member of the Australian Regional Immunisation Alliance. Ketaki contributed to the authorship of the Australian Immunisation Handbook and statements from the Australian Technical Advisory Group for Immunisation. I'm a member of the Drug Utilisation Subcommittee of the PBAC. The views of the guests and the host on this podcast may not represent Therapeutic Guidelines or Australian Prescriber. I'm David Liew and once again, thank you for joining us on this Australian Prescriber Podcast. [This interview was conducted on 21 October 2023.]