Transcript of RSV vaccine update and Shingrix
Jovi Stuart: Good evening everyone and welcome to tonight's webinar, RSV Vaccine Update and Shingrix vaccine rollout. My name is Jovi and I am your RACGP representative for this evening. We are joined tonight by presenters Professor Nicholas Wood and Dr. Jean Li-Kim Moy, and our facilitator, Dr. Linda Mann.
Before we continue, I would like to make an acknowledgement to country. We recognise that the traditional custodians of the land and sea on which we live and work, and we pay our respects to Elders past, present and emerging. I would also like to acknowledge any Aboriginal and Torres Strait Islander colleagues that we have joined us online tonight. I myself am joined from Cammeraygal Land on Sydney's North Shore.
I would formally like to introduce to you our speakers for this evening. We have Professor Nicholas Wood is a senior staff specialist general, pediatric pediatrician and professor in clinical vaccinology at the University of Sydney. Nick leads the New South Wales Immunisation Specialist Service and coordinates the Immunisation Adverse Events Clinic at the Children's Hospital at Westmead, and he is also the senior investigator on the Primary Health Network Immunisation Support Program. Nick is interested in maternal and neonatal immunisation as well as research into vaccine safety, including genetics and long-term outcomes of adverse events following immunisation.
Dr. Jean Li-Kim Moy is a staff specialist in immunisation at the National Centre for Immunisation Research and Surveillance. John is involved in the Research to Inform Policy team, which provides support to the Australian Technical Advisory Group on immunisation, also known as ATAGI. He has assisted ATAGI in its evaluation of numerous vaccines including influenza, meningococcal, Covid 19, RSV and herpes zoster vaccines. He is also a general pediatrician working in community paediatrics and neonatal care.
Dr. Linda Mann is a Fellow of the RACGP and a member of the RACGP Antenatal and Postnatal Care Network. Linda has both local and international medical experience, especially in genetics and women's health. Linda is a GP representative in various national and local government committees and is an experienced medical educator.
So welcome to all of our speakers tonight and I will now hand over to Linda to start off this evening.
Dr Linda Mann: Tonight we have some learning objectives, by the end of this online activity, you should be able to outline disease pattern for herpes zoster or shingles and vaccine coverage in elderly individuals, outline eligibility for free Shingrix vaccine under the National Immunisation Program, outline clinical recommendations on the Shingrix vaccine schedule and administration for immunisation providers, outline prevention strategies and the global burden of RSV disease in New South Wales and Australia, summarize the RSV vaccine and monoclonal antibody technology landscape and the various clinical trials, and discuss the efficacy and safety of the RSV vaccines in different cohorts. Now, in addition to our speakers, because of the very recent rollout of the Shingrix vaccine, we are lucky enough to have Sonia Ellis, who is the manager of immunisation for the Ministry of Health, just to give us a few words about that.
Sonya Ennis: Thanks very much, Linda, and good evening, everyone. Lovely to be able to give you some advice about the Shingrix program. Hopefully you have received information that has been sent out from the Ministry of Health with regard to the rollout of the program. The information on the left was quite a detailed document that we distributed before the 1st of November to all GP's, Aboriginal medical services, pharmacists, immunisers and residential aged care facilities, and on the right we have been discussing the program with the RACGP and the AMA and also our pharmaceutical bodies, and we decided to put out a joint statement with regard to the restrictions that had to be added to the program and the initial stages.
As you are aware, the program commenced on the 1st of November. You have been able to order vaccines from the 30th of October. Initially, we had a restriction on the vaccines of about 5 to 20 per account, but we have been able to increase that by up to 40 for some providers and that depends on the number of immunisation providers or GP's that you have at your facility, at your practice. The reason for these restrictions is the amount of vaccines that have been provided to us from the Commonwealth are the initial stages of the rollout of the program, but the Commonwealth do advise us that the supply restrictions are expected to ease in early 2024, and we are monitoring this daily with the amount of vaccines that are being distributed and being ordered by providers, and I am pleased to say that since the program started two weeks ago, almost 90% of GP providers that have an account with us have ordered vaccines, but do acknowledge that the vaccine amounts are restricted, and we are monitoring that really closely so that we can increase those restrictions. Hopefully over the next couple of weeks. It is recommended advice from the Commonwealth that providers should prioritise their highest risk patients, and Zostavax has been removed from the program. However, you may continue to use Zostavax for people aged 70 years who prefer to receive the vaccine until they expire, I believe some of them expire towards the end of next year. But if you don't have any patient demand, just discard the vaccines as pure routine discarding processes.
I did want to highlight the difference between vaccine distribution from the New South Wales Vaccine Centre and the Commonwealth, because I understand that there may be delays in Covid vaccines that are being distributed via the Commonwealth processes. With the vaccines that are distributed from New South Wales Health, from the state vaccine centre, if you are in a metropolitan area, you will receive those vaccines between 1 and 2 business days. If you're in a rural and remote regional area, it is around 2 to 4 business days and we have distributed quite a lot of vaccines. I think in the first two weeks we have distributed over 40,000 doses, and that's in concurrent with the amount that we have been provided with. As I have said before, we hope to increase those ordering as time and as weeks go on, and that will ease in the New Year. And that is really all I needed to share with you. If you don't have the materials that we've sent out, please contact your local public health unit. They are also available in our New South Wales Health website, so please have a look there.
Jovi Stuart: Thank you Sonya. Sonya is actually going to still be around during this presentation. If you have questions or someone comes late and goes, oh, but haven't heard about the shingrix, please do enter a question or a request into the Q&A so that we can respond without addressing it directly. Hand back over now to Dr Jean Li-Kim Moy.
Dr Jean Li-Kim Moy: Thanks for asking me to talk about herpes zoster and the Shingrix rollout. So first of all, I would like to begin by acknowledging the traditional custodians of the land on which I am meeting you today, the Gadigal people of the Eora nation, and pay my respects to their elders, past, present and emerging.
Firstly, I think most of us here would know what shingles is, also known as herpes zoster. So, shingles is a reactivation of latent varicella zoster virus, which has been acquired during a primary chickenpox infection. It stays latent in the dorsal root ganglia until it reactivates and then reactivates the shingles. Typical symptoms are pain and also a dermatomal rash, which is often unilateral, as you can see here, stopping in the midline. You have a picture here of the characteristic vesicular lesions and then often as they progress, they may become somewhat haemorrhagic in the bottom picture there. The complications of shingles, most notably is the acute pain that is associated with that and that is an acute neuritis and that has both a nociceptive component as well as a neuropathic component, where there is abnormal nerve signalling. The common complication from from that is to develop post-herpetic neuralgia, where the pain persists more than three months after the onset of herpes zoster, and that can occur in up to 30% of cases. Again, the risk of that occurring increases with increasing age. Other side effects can include herpes zoster ophthalmicus where it involves the trigeminal nerve and here you can see in this picture it also affects the eyes and has a risk of blindness. Other complications can include secondary infection of the skin lesions, as well as disseminated infection or systemic involvement of things such as the brain, liver, lungs, etc.
So why does shingles occur? It occurs because there is a reduction in the T cell mediated immunity, which is important for continuing to suppress the varicella zoster virus throughout life. So, we all have antibodies which are present after the initial infection and those antibodies may be important in preventing primary varicella, but they don't prevent shingles. So, what happens is over time with age there is a general weakening of the immune system, and that is called immunosenescence and as people get older, the weaker immune system and reduced cell mediated immunity allows the virus to reactivate. So, the risk factors are obviously increasing age and immunocompromising conditions, especially those which impair T cell function, and those can include HIV, haematological malignancy, stem cell or solid organ transplants, as well as immunosuppressive treatments such as steroids, biologics, or disease modifying antirheumatic drugs. The exact trigger that causes a reactivation can be unclear, but it's postulated to include things like stress or physical trauma, or intercurrent infection or illness. So how commonly does shingles occur? It is quite a common condition, and in everybody's lifetime, up to 30% of people will have a shingles episode, and if you happen to to live till 85, that that risk could be 50%. As you can see, the risk increases with age and from around 50 or so there is this acceleration of the risk with a higher incidence and that is a pattern that is seen across all countries.
The National Shingles Vaccination Program started in November 2016 with Zostavax, and that was the live zoster vaccine, which was originally funded at 70 years of age, although it was registered from 50 years of age. It had quite a generous catch up program for 71-79-year olds, and that has continued until the 1st of November, when it was replaced by the Shingrix vaccine and availability will obviously decrease with time now. The main issues with Zostavax there was only suboptimal uptake and I will show a slide on that, but as well, there was the issue of only sort of moderate efficacy against herpes zoster. Here you can see around 51% efficacy against herpes zoster. Better protection, 66.5% efficacy against post-herpetic neuralgia. The other issue was that as you got older, the efficacy decreased. So particularly for those over 80 who probably have the highest risk, the efficacy was non-significant in that population. And lastly, there was the issue that there was waning of protection. So, there was probably good protection for about five years, but then sometime between 5 to 10 years after vaccination, there was waning to sort of insignificant levels of protection. Lastly, there was also the issue that it was a live vaccine, so it was contraindicated for people who were severely immunocompromised and they can be a population at risk of an increased risk of herpes zoster. In fact, there were people who were inadvertently given a Zostavax and that has led to three deaths since the program was started. Here you can see the coverage. The coverage has been sort of moderate. So around 30 to 40% for the 70 to 71 age group. A little bit higher in the catch up cohort of 71 to 79. So anywhere up to about 55%. So the new vaccine came along, which is Shingrix, which is a recombinant zoster vaccine. It is a subunit glycoprotein E-vaccine with this AS01B adjuvant, which is the main reason that we get such a good immune response to it. It is a non-live vaccine, so it can be safely given to immunocompromised people. It was registered first in July 2018 from 50 years of age, and that registration was expanded in December 2021 to include immunocompromised people from 18 years of age. So, in contrast to Zostavax, which was a single dose, it is now a two-dose schedule, and there is a 2 to 6-month interval between the two doses and that can be reduced to 1 to 2 months for people who are immunocompromised. So, comparing Shingrix with Zostavax, here you can see shingrix in comparison to Zostavax has very high efficacy. So, we are talking roughly 90 to 97% efficacy against herpes zoster and 89 to 91% efficacy against post-herpetic neuralgia. These were the data from the licensing clinical trials. Again, also different to Zostavax is the fact that those high levels of efficacy are retained in people who are elderly. So for the the value for those 50 years and above and 70 years and above are roughly similar. Now as we are getting more and more follow up time from the original licensing trials, what we have seen is that there is good duration of protection. So here the immunogenicity data shows a persistently high anti-glycoprotein antibodies even up to year ten, being higher than pre-vaccination and also more importantly, the cell mediated immunity also remains high. When they look at efficacy in that original cohort of participants in the clinical trials over 50, what you can see is there is a gradual, but very slow waning of efficacy against herpes zoster over ten years, such that if you are looking from the time of vaccination to ten years, the cumulative vaccine efficacy remains about 89% over ten years, and if you are looking from about year five to year ten, it is around 81.6%. So, at this stage, there is no current indication of a need for a booster vaccination.
The adverse events with shingrix. Shingrix is a moderately reactogenic vaccine, and you can see that comparing to values from the clinical trials of zostavax against placebo versus shingrix against placebo. You can see up to 80% of people will have injection site reaction, mostly pain and also an elevated proportion will have some systemic side effects, including myalgia, fatigue, headache, fever, etc. So about 1 in 10 people gets side effects which are severe enough to disrupt normal daily activities, but generally it is short lived anywhere between 1 to 3 days in duration. So, it is important to warn patients who are receiving shingrix about these expected side effects, because if people experience unexpected side effects, they may have second thoughts about completing the two-dose schedule, which is important.
Just a quick mention about Guillain-Barré syndrome and shingrix. So, this this was a safety signal picked up in the US from some observational studies where they looked at the risk of GBS in a risk window quite soon after vaccination day 1 to 42, and compared it to day 43 to day 183. Different ways of looking for GBS, they both found that there is roughly 2.8 or 5 times increase incidence of GBS and they found that roughly three attributable cases per 1 million doses. So the risk is still very small. And it's important to note that this was one study that did find this association. When they used prospective active surveillance in a different cohort study using the US Vaccine Safety Datalink, looking for ten pre-specified health outcomes and comparing it either to a historical cohort of Zostavax recipients, or to a cohort who were just having annual well person visits, you can see, as they followed more and more doses, the risk of GBS was coming closer and closer to one. They found no sustained increase of GBS with Shingrix in this particular active surveillance study.
When they looked at real world effectiveness of Shingrix, what they are finding is that it is roughly matching that seen in the clinical trials. So, 80 to 88% across all ages. Another effectiveness study out of the US confirms that you do need that second dose to really sort of get the good level of vaccine effectiveness against herpes zoster. The shingles vaccination program has switched over from November. As we have heard, Shingrix has replaced Zostavax. So Shingrix is now funded from 65 years with no upper age limit. Aboriginal and Torres Strait Islander people are funded to receive it from 50 years of age because of their increased burden of zoster. It is also funded for high risk immunocompromised. So for conditions initially from 18 years of age. So, these are the conditions thought to have the highest risk of herpes zoster including haematological stem cell transplant, haematological malignancy, solid organ transplant, and advanced or untreated HIV, generally thought to be those with a CD4 count of less than 200. So importantly, funded Shingrix will not be available for those who have had a funded Zostavax within the past five years, again, that is because Zostavax is thought to provide a reasonable protection against herpes zoster for at least that five-year period. So the recommendations are also listed in the updated Australian Immunisation Handbook. It is important to know the difference between what is recommended and what is funded. The funded group is a smaller group within the recommended group. So people who are aged 50 and above are recommended for zostavax vaccination, but only those 65 and above are funded. So, all people who are immunocompromised 18 and above are recommended, but at this stage, only those four groups with severe immunocompromised are funded, although other conditions and therapies considered moderately immunocompromising are being sort of considered for funding at a later date. So, people who are household contacts of somebody who is immunocompromised are recommended but not funded, and Aboriginal and Torres Strait Islanders over 50 are both recommended and funded.
Contraindications to the zoster vaccine. So, for Shingrix only if there is anaphylaxis to a previous dose or a component of the vaccine. For those people who are continuing to use Zostavax, it is important to remember that severe immunocompromise is a contraindication and that anyone who has been considered for vaccination should be screened using the Zostavax Contraindication Screening tool available in the Immunization Handbook to try to identify immunocompromise.
One important question is what age should people be vaccinated? People can receive the vaccine from 50 years of age, and people should be routinely recommended to receive it from 65 from the NIP, but people who are 50 to 64 can be prescribed the vaccine via private prescription. So it is important when you are deciding about that, to balance the fact that the risk of shingles starts to increase at 50 years of age, but it is only when you start to get older, you know, 65 and above, where the risk increases even further, and so you should balance the increasing risk of shingles with increasing age versus the waning of protection over time that we saw with Shingrix, even though it is quite slow waning. You might consider the patient preference, whether they have a desire to be protected as soon as they are eligible and also consider when they might become eligible for free Shingrix. So, somebody who is 63 or 64, may be comfortable waiting for a year or two, if they know that they're going to get the vaccine for free once they reach 65. Aboriginal and Torres Strait Islander people should be routinely vaccinated from 50 years and above, and for immunocompromised people who are eligible from 18 years, again, age remains the biggest determinant of risk. You may consider their immune status. Do they have one of those funded conditions which carry the highest risk, and if so, you might vaccinate them early. People with other autoimmune conditions may have lower risk and they may be eligible via private prescription. Again, if you are vaccinating someone in their 20s, you have to consider about that issue of waning and know whether it is the most appropriate time to vaccinate them. Some young immunocompromised patients with some conditions may have less of a risk than an older person aged 65 who is non-immunocompromised.
Linda Mann: There has been a question that is very relevant to this, and that is about people who do not have solid organ conditions but who have, for example, CLL Stage 0, who we in general practice land would consider to be immunocompromised, but, you know, they are going to be that way for a long time. How do they fit into the current environment?
Dr Jean Li-Kim Moy: They would be eligible under haematological malignancy. So, we consider CLL to be a haematological malignancy, so they should be eligible.
The PBAC is considering funding for other risk conditions. The situation may change. Some of the people who currently might have to pay for the vaccine in the next year or so, the vaccine may become funded for them. It is important to watch this space.
You can see here we are looking at the incidence rate of herpes zoster and in the youngest group 18 to 49 you can see some of these people with rheumatoid arthritis inflammatory bowel disease who may be immunocompromised may actually be immunocompromised at a fairly low level, and their incidence rate for herpes zoster is still lower than a non-immunocompromised person who is 65 to 69. They may be more appropriate to vaccinate once they sort of get a little bit older, to 50 to 59-year age group. Again, it is a personal discussion with each patient.
The main practice points: shingrix can be given to people who have previously had shingles. So we aim for an interval of around 12 months for immunocompetent and three months for those who are immunocompromised. Shingrix can be given to people who have previously had Zostavax. Again, we aim for a minimum 12-month separation, but noting that NIP condition of needing to have been five years after funded zostavax. You don't need to know if you have had chickenpox or have serology to prove it before giving shingrix. Most people in the age group were considering vaccinating will have had exposure to varicella zoster virus. But if serology happens to be done and there is no previous history of vaccination or chickenpox, then perhaps you could consider varicella vaccination instead if the person is safe to receive a live varicella vaccine. Co-administration with other vaccines is acceptable, but you might get a slight increase in reactogenicity. Patients who present greater than six months since their first Shingrix dose, that means if the interval between the two doses is longer than six months, don't need to have the schedule restarted. And patients who have paid for their first dose of shingrix can receive the second dose under the NIP if they meet eligibility criteria.
Shingrix and chickenpox. Shingrix is not indicated for primary protection against chickenpox. No studies examine that. People should have varicella vaccine instead.
Shingrix is now available for the outlying groups. PBAC will consider other immunocompromised groups in the near future. There are lots of things to consider about the best age to vaccinate and completing that two-dose schedule is important.
A list of the resources are available, including from the NIP web page, some fact sheets from NCIS also helpful for providers and my references are there.
Prof. Nicholas Wood: Hi, everyone. So, in the next little while, we will just quickly highlight for you the road ahead with RSV vaccines. Just also to acknowledge country which I know we did earlier, pay respects to elders past present and leaders emerging.
In the next little while I will highlight for you what we know about the RSV burden in Australia. Some of the strategies to prevent RSV, particularly in those over the age of 60 and our youngest infants, and there are two real strategies there, the maternal vaccination and the monoclonal antibodies. And to do that, I will show you the trial data, the immunogenicity and safety, and a little bit from what the US experience is.
RSV is one of the top infectious diseases and respiratory infections globally. In fact, it is one of the highest causes of death outside of high income countries like US and Australia, causing death in children. So, it really is a high burden respiratory infection. We have published a paper showing the hospitalisations in Australia over this decade in the MJA and interestingly, this was one of the largest papers to look at this RSV burden. In that decade there were over 60,000 hospitalisations and in the next slide I will show you some of the age groups. You can see here that the biggest age group on the panel A on the left, is the youngest kids aged 0 to 2 months. If you look at the Y axis, you will see that it goes up by thousands per 100,000 population. Fairly stable over that decade, but the highest rates in the 0 to 2 months and then it drops down 3 to 5, 6 to 11 and 12 to 23. Panel C shows you the hospitalisation admission rate by age in the over 5's, and you can see there is a sharp uptick in the over 65 seconds beginning in around about 2011, and this is most likely because of new availability of diagnostics, where we could do respiratory panel testing and so able to find more cases, hospitalise them than we knew before. So, based on this, the targets that the pharmaceutical companies wanted to target the prevention are the under six-month olds and the over 65 seconds.
Next slide. This is a bit of a comparison in New South Wales of flu and RSV. This is data from this year and you can see that again while flu the Y axis is in the 500 to 1500, RSV is still a high burden pathogen and, you lasting for a longer period in this graph showing from March through to July. So that is the new local data.
Next slide. Interestingly, there is some evidence now that there are negative longer-term outcomes of RSV infection. This is a graphs which are on the left hand side, the case control study, which shows that if you had previous RSV infection, that you are more likely to end up with asthma compared to the controls and the same thing in the table there, the same concept, that if you had been treated with palivizumab, which is a way to reduce the burden of RSV first generation antibody, we saw a reduction in wheezing in infants. So, there are some longer-term outcomes of RSV.
Next slide really as I said shows you that targets are maternal vaccination or early infant vaccination for the under ones and the over 65's.
Next slide. The whole vaccine field was set back by this paper back in the late 1960s, which in the first-generation RSV vaccines showed that prior exposure through vaccination actually led to vaccine enhanced disease, and this really stopped the production or the interest in RSV vaccines for many decades and until recently.
Next slide. The real target of this RSV vaccine is the F-protein and a little bit like the Covid spike protein, the F-protein is the fusion protein for which if we can generate antibodies and cellular immune responses to, we can hopefully prevent RSV infection.
Next slide. This slide shows you the different approaches to making the vaccines, from live attenuated vaccines to protein based vaccines to immunoprophylaxis, and there is definite interest in it because of the burden of of the disease and a lot of companies throwing money in trials, and you can see here that many are in the Phase 1 stage and in the red box are the three products that are market approved in the US and which we will talk a little bit more. There are two protein-based vaccines from GSK and Pfizer and an immunoprophylaxis which is called palivizumab, which is also a market approved, but they are very healthy pipeline for vaccine development.
Next slide. So on to the elderly in RSV prevention. So, there are two vaccines that have been approved in the US. There is Arexvy by GSK and ABRYSVO by Pfizer. These are the two vaccines that have now been approved and are currently rolling out in the US in preparation for their winter.
Next slide. So, there are a couple of key papers. This is the GSK paper and you can see here what they looked at was the prevention of RSV across only two seasons, but still showing pretty good protection against lower respiratory tract disease and against medical attendance, lower respiratory tract disease, around about 80 to 85% in season one. It dropped off a little bit in season two, but certainly was evidence of good protection in season one.
Next slide. This is the Pfizer product. And again, the same idea, season one 80 to 85% vaccine effect efficacy, dropped a little bit off in season two, but pretty good vaccine effectiveness. It was based on this effectiveness and the next slide which I will show you some of the safety data that the vaccines were licensed.
Next slide. The vaccines were generally very safe. However, of interest, there were a couple of what we now call adverse events of special interest and you can see here on this slide that there were six cases of inflammatory neurologic events, particularly Guillain-Barré syndrome, across those trials and there were three in the GSK and three in the Pfizer. There was also a small imbalance in the outcome of atrial fibrillation, with more cases amongst the vaccine recipients compared to placebo and what is not known in the current timing is that either of these adverse events, Guillain-Barré or atrial fibrillation, whether they occurred by chance or whether the RSV vaccine increased the risk. However, they are being actively looked at in a range of safety monitoring systems in the US, so we will get more data on those very soon.
Next slide. So, it was based on, as I mentioned, quite positive efficacy data and the safety data that earlier this year, the ACIP, which is the US equivalent of ATAGI, recommended that adults age over 60 years of age could get a single dose of RSV vaccine and they have used what they call shared clinical decision making. The groups that are really the most recommended for this are shown on the next slide and that is these groups here, which are very similar to the groups who recommended the influenza vaccine. So those with chronic lung, heart, neurologic disorders, immune compromised, endocrine, kidney and liver, and those that are in aged care facilities. So, it is the usual type of people that we would strongly recommend the influenza vaccine for, or also recommended for the RSV vaccine.
Next slide. In terms of co-administration of RSV vaccines, the US guidelines say that we can give the RSV vaccines together with the flu and the Covid pneumococcal. Having said that, there is not a lot of safety data out there on this, so it would certainly be something that will be watched closely in the US, but based on first principles, these vaccines are being recommended to be given in the US as a co administered product.
Next slide. Now we are just turning to the early infant RSV protection and as I mentioned, there are two options, the infant monoclonal and the maternal vaccine.
Next slide. In July of this year, the FDA approved a new drug, which is a monoclonal antibody called nirsevimab.
Next slide. It is a monoclonal antibody very similar to palivizumab. However, rather than requiring monthly injections, it has a much longer half life and therefore can protect infants for the entire RSV season. So that is much more of an advantage compared to Palivizumab, and means we can get away with one vaccine to a young infant and hopefully last the entire season.
Next slide. There are a couple of studies that have been done, but the key study is what is known as the Harmony Study with over 8000 infants enrolled across the US, UK, France, Germany, etc. As shown here, the primary endpoint was RSV hospitalisation and next slide shows you the key data. So, it was very effective against RSV hospitalisation, over 80% effective and very effective against severe disease and also a very, very safe product. It is a monoclonal antibody. The question is whether it really is a vaccine or not, but certainly a bit like hepatitis B immunoglobulin, it is an antibody, very safe product and there were no real differences between control and the nirsevimab arm. Again, based on the safety and efficacy data, it has been licensed in the US and is currently rolling out.
Next slide. The other way to approach the early infant disease is, as we do with flu and pertussis, is to vaccinate the pregnant woman and this is the key study, the Metis study and you can see here in this particular Panel A, what we are showing you is the vaccine effectiveness of the maternal RSV vaccine compared to placebo, and again, pretty good, 70 to 80% effective in the first 100 to 150 days after birth. So similar proof of principle like we do with flu and pertussis, vaccinating that mum, she makes antibody to RSV, crosses the placenta, baby starts life with a good amount of RSV antibody and is protected.
Next slide. They looked at the safety in the mother and as you would expect in the infant, and no real differences really, in the mums who got placebo compared to the vaccine, and again, there were no real concerns in the infants and they were followed up. There was a little bit of a hint of early prem delivery in the mothers who were given the RSV vaccine, but the numbers weren't quite enough to make a definite answer on that, and so that will be something that is also watched. Slightly increased chance of prem delivery, but not definite yet.
Next slide. Again, based on the safety and efficacy data, the US is now recommending that to prevent infant RSV infection, practitioners can either use nirsevimab or maternal RSV vaccine.
Next slide. The interesting thing is you don't want to use both and so there are algorithms that have been developed in the US, which will be similarly developed in Australia when these products become licensed, and that will revolve around whether the mother was given the RSV vaccine or not, and then that will determine whether the baby can get the nirsevimab or not. So, these sorts of algorithms we don't yet have developed for Australia, but will likely to be developed when these products come to market.
Next slide. The next steps are that these particular products are under evaluation by the TGA. I think we are expecting an answer on them very soon. Once we have the TGA authorisation, then they go through ATAGI to develop clinical guidelines, recommendations of their use, PBAC assessment as to whether or not they can meet cost effectiveness for inclusion on the National Immunisation Program and then there will be a range of educational materials developed for consumers and providers.
Just to highlight that these products are coming, that they certainly have rolled out in the US, there is no real-world effectiveness or safety data yet in the post-marketing space. We will expect to see some of that in the next few months. They are not far off being rolled out in Australia, not yet through the initial hurdle, which is a TGA hurdle, but will probably happen, I suspect, next year. Then it becomes an issue about supply.
Dr Linda Mann: You demonstrated the significant increase in RSV infection, which you indicated could be because we now can find it in folks over 65, I have to say, in my own clinic, it seems to me that RSV has appeared as a significant cause of very, very bothersome respiratory infections in adults in a way I have never seen in my gray haired many, many, many years of general practice. Has there been any research in the way there has been for children in the use for older folk?
Prof. Nicholas Wood: Is it a great question, Linda. To be honest, we haven't really got our burden assessments of this virus in the adults as sorted as we would like to have. So I don't know if what you are describing as sort of a troublesome ongoing chronic cough, which whether that is just a different strain of RSV, there are two types of RSV, A and B, or whether just because now we can actually test for it and finding it a bit like, you know, human metapneumovirus, which was probably always around, but now we can pick it up on the panels along with para influenza, etc, so I think there is no doubt that it is a troublesome virus for the over 65's and hence that is why the vaccines have been targeted for that age group, but the actual real burden data we have in Australia is we are playing catch up a little bit, I think.
Dr Linda Mann: We have some time for any other questions that anyone wants to put into the Q&A for our speakers to respond to. It looks to me like people have had their questions answered, however, which is great. It is wonderful we have actually achieved our learning objectives. We have outlined the disease pattern for herpes zoster and vaccine coverage in elderly individuals, we have outlined the eligibility for free Shingrix vaccine under the National Immunisation Program, for which we must say thank you to Sonia. We have outlined the clinical recommendations of the Shingrix vaccine schedule and administration for immunisation providers. We have outlined the prevention strategies and the global burden of disease in New South Wales in Australia. We have summarised the RSV vaccine and monoclonal antibody technology landscape and the various clinical trials and we have discussed the clinical, the efficacy and safety of the RSV vaccines in different cohorts. We do have a couple of extra questions. There is an adult immunisation health pathway which you can find on your local Health Pathways and certainly if you want something that is really pretty up to date and may be in fact equivalent across the state, but I'm not quite sure, absolutely, go to your local health pathway, and in fact it is across New South Wales and it will have the same information, so it is reliable and has come from all the right sources and just because I used to work for Health Pathways is not the reason I am recommending this. Any other questions or comments from the people listening?
I think we're done. Thank you very much to our speakers. I will hand back over to Jovi.
Jovi Stuart: Perfect. Thanks so much, Linda. I would also like to extend my thanks to Nick, Jean and Linda for presenting this evening and also to everyone who has joined us online. I hope you have a good evening, everybody.
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