Recommendations, Indications for Vaccines Against RSV
In this multidisciplinary roundtable discussion, Albert Rizzo, MD, interviews Barbara Taylor, MD, MS, and Leonard R. Krilov, MD, about recommendations and indications for vaccines against RSV, including in adults, pregnant women, and children, uptake, efficacy, and monoclonal antibodies available.
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TRANSCRIPTION:
Albert A. Rizzo, MD: I am Dr Albert Rizzo, Chief Medical Officer of the American Lung Association. I'm here with two other experts. We're going to continue talking about RSV and the new vaccines that are available this year. Dr Krilov could please introduce yourself?
Leonard R. Krilov, MD:
Sure. Hi, my name is Lenny Krilov. I'm Chair of the Department of Pediatrics and Professor of Pediatrics at NYU Grossman Long Island School of Medicine and NYU Langone Long Island Hospital, also a pediatric infectious disease specialist.
Albert A. Rizzo, MD:
Dr Taylor?
Barbara Taylor, MD, MS:
Hi. It's very good to see everybody. My name is Barbara Taylor. I am a professor of infectious diseases at UT Health San Antonio, the Joe R. and Teresa Lozano Long School of Medicine, and I am an adult infectious diseases specialist.
Albert A. Rizzo, MD:
Thank you both for being here. So RSV infection, we know is very prominent in infants. We also know in adults, it's becoming a concern, especially for older individuals, especially those with chronic conditions such as asthma and COPD. And we need to use multiple channels to get this information out. Right now, we have multiple vaccines, updated COVID, yearly influenza, not to mention pneumococcal and diptheria and tetanus vaccines, and we're asking a population to stay up to date. We know that vaccine fatigue sets in. We also know there's been underlying mistrust in science over the last couple of years in certain segments of the population, and we're concerned that vaccine uptake will not be as optimal as we'd like from a public health standpoint.
Now, aside from that, let's start by discussing these RSV vaccinations that are being recommended. Let's start with the older adults with certain comorbidities. I'll turn to Dr Taylor to start talking about the vaccine's availability now.
Barbara Taylor, MD, MS:
So this is an exciting development for those of us who see older adults, particularly older adults who are immunocompromised. Over the summer, the FDA approved vaccines for adults aged 60 or over. It is interesting; the way that the recommendations came down from the advisory committee on immunization practices is that they really encourage shared decision-making around these vaccines. So, there are two vaccines that are potentially available, and they are emphasizing that they want providers to have a conversation with patients about the risks and benefits of these two vaccines.
The vaccines, briefly, one is called Arexvy, it's made by GlaxoSmithKline. The other is called Abrysvo made by Pfizer. They're both very effective. They actually had very similar efficacy across their trials. The trials were very robust with 25,000 and then 34,000 participants in either trial and a vaccine efficacy of 80% or higher against lower respiratory tract disease with RSV in older patients. So, it's exciting to have these as tools. I think because of some of the rare side effects in some of these vaccines, they really do want providers to talk to individual patients about the risks and benefits of the vaccines themselves.
Albert A. Rizzo, MD:
And Dr Taylor, based on the fact that multiple vaccines are available now, can individuals get the RSV vaccine around the same time as they get the COVID or influenza vaccine if that's available?
Barbara Taylor, MD, MS:
Yes. So they made a recommendation. There was actually a trial of RSV vaccination simultaneous to influenza vaccination, so we have some data on that, and the ACIP made their recommendations based on that saying that you can give these vaccines simultaneously with other vaccines, so people can get their RSV and their influenza vaccines at the same time. There are not real data about RSV and COVID vaccinations simultaneously, but they're extrapolating the data from the trials that gave RSV with influenza together.
Albert A. Rizzo, MD:
Thank you. Now, I'd like to switch to a discussion of the new modalities for infants and children. Let's start with the vaccine for pregnant females.
Leonard R. Krilov, MD:
So the same vaccine that's licensed from Pfizer for older adults is also approved for pregnant women. The approval is 32 to 36 weeks gestational age. The trial included women earlier in gestation, but based on the strength of the data, it was limited to this group. And the idea is that by immunizing the mother, they would then passively pass antibody to this fusion protein of the virus that the vaccine is made of onto the babies and provide protection.
And indeed that's what was seen with, again, a 70+% decrease in lower respiratory tract disease and medically attended lower respiratory illness in the babies born to mothers who got the vaccine over a five, six month follow-up period. So it is approved, and again, similarly, although not as completely studied in smaller numbers, can be given concomitantly with the other recommended vaccines in pregnancy if they haven't been given earlier, specifically DTaP, influenza, and COVID vaccine as well.
The concerns about the vaccine that have been raised are that if the baby is born prematurely, they would miss out potentially on the bulk of maternal transfer of antibodies, so they would be eligible for the second modality that we'll talk about in a moment. And specifically giving the vaccine for the benefit of the baby with no clear-cut benefit to the mother because there's not a lot of data, there's no real data, on RSV in pregnancy and its impact on the mother to protect the baby. But the benefits appear clear, and now that we do have increasing experience with vaccination of pregnant women showing it can be safe as well as effective, this has been approved. Mothers do come for their prenatal visits, so it seems like there is a good chance to capture and provide this protection at that time.
Albert A. Rizzo, MD:
Great. Then I know we also have a monoclonal antibody. How does that fit into the scheme of things for these children?
Leonard R. Krilov, MD:
So, we've had a monoclonal antibody, palivizumab, for 25 years. The problem with it was the way it was made from old fusion technology and humanizing it was a very expensive product. Plus as a typical IgG molecule, it has a half-life of only 21 to 28 days, so it requires monthly injections. So based on the monthly injection and the cost, its indications are limited to the highest-risk premature babies or those with lung or heart disease, which is only about 2% of the birth cohort, even though, as we've discussed, RSV is a significant issue for all babies in their first year of life.
So, over the last several years, major advancements in technology, specifically the recognition that by just changing three amino acids on the FC receptor end of the IgG molecule, can extend the half-life from 21 to 28 days to five to six months. And there's one now FDA-approved and ACIP guidance for and another in development that is maybe a year or two behind that also provides this type of protection and, again, in the clinical trials shown to be safe and effective, and also a 75+% to 80% decrease in lower respiratory tract hospitalization and medically attended illness over this early period infancy.
So based on these data, this long-acting monoclonal or passive immunization, the one that's approved, nirsevimab, received ACIP recommendation for all babies up to eight months of age going into their first winter. Unless mothers had gotten the maternal vaccine, then they wouldn't necessarily be candidates unless they were high-risk premature, then they would actually potentially get both.
For very high-risk babies, extremely premature, those with lung or heart disease, even a second does in their second season, a second dose at 8 to 19 months going into their second winter would be recommended. What we're struggling right now with now that it's just been approved and coming is how do we do this logistically, and this is a real challenge. One for those babies born in season, ideally would be to give it during their birth hospitalization. Although the study mostly was not babies right at newborn, it was in their first month or two, but it's considered likely to be fine. It could be given with other vaccines, so they can get their hepatitis B routine immunization at the same time.
From a logistic end, we're trying to on a system level at all hospitals, look at the finances, because there's no extra reimbursement for the drug, and you're talking about potentially 80% of your newborns, even if it's much less expensive as a recombinant antibody than palivizumab, it's still a significant expense.
On the other side of the coin, gearing up practices to give a monoclonal antibody and give it without a long delay from discharge, is another challenge. Recalling babies who were born in August and September, who would be eligible for their first winter and aren't in the hospital, and getting them back. So since this was just approved in August and is just being shipped now, everybody's struggling with figuring out the best way, but it really is a major advance in protection for these babies.
Albert A. Rizzo, MD:
So at the time of this recording, which is early October, sounds like there's still a number of challenges and hurdles logistically to get it into the right individuals. Is the same thing occurring with the adult vaccine, Dr Taylor? Do you see any acquisition problems?
Barbara Taylor, MD, MS:
So yes, and I think there are two challenges right now with the adult RSV vaccine. One is just acquisition problems, and I think it is available in pharmacies. And so they're people who generally are pro-vaccines and have access to vaccines and are interested in vaccination can have access to it if you can go to your local pharmacy and get it. However, I think there has not been a real focus on rollout into communities without ready access to insurance or access to care, which is one challenge.
And I think the other is just a bandwidth challenge. I was in clinic this morning and we're giving flu shots and we're trying to get everybody to go downstairs where the negative-80 degree freezer is so they can get their COVID booster, and then we also have RSV. And so I think it is a real, "How do we get all of these recommendations and promote them appropriately and make sure that the people who are most at risk for adult RSV really do have access to the vaccines?" And then there's the added complication of the ACIP recommendation of shared decision-making, which means that you're not really supposed to just walk into a pharmacy and demand it. You're supposed to have a conversation with a provider about it before you get it. And so that creates an additional challenge.
Albert A. Rizzo, MD:
Some challenges, great. Well, I wanted to ask another question. It goes a little bit behind the vaccine development. During the development of the COVID vaccine, we heard a lot about the spike protein and the ability of the virus to evolve and mutate into different variants, which is still occurring. Now with RSV, I've read about the pre- and post-fusion form of a surface glycoprotein that seems to be important in the development of the current vaccines for RSV. Do either of you foresee the same issue of mutation and multiple variants occurring and the need for vaccine reformulations with the RSV vaccines?
Leonard R. Krilov, MD:
So from my having looked at this for a long time, there was a killed RSV vaccine 40 years ago that set RSV research back decades, because not only didn't it work when immunized babies were exposed to natural RSV, they got severe disease and even mortality was observed. So the molecular biology has really been worked on. It's actually the F or fusion surface protein that's critical. As you mentioned earlier, Dr Rizzo, there's a pre- and post-fusion form and probably intermediates as the virus binds to the host cell, but it has been shown that the pre-fusion protein is the critical part. And despite the fact that this virus does drift and change, I shouldn't use drift, that's specific to influenza, but it does change over time, this part seems to be really conserved. And so although it has to be monitored for what are called escape mutants over time, I think it's less likely, certainly, than COVID variants have been.
And I think the best support I can give for that is if you look at palivizumab that's been approved for 25 years, there have not been really escape mutants that have been clinically important or resistant to palivizo. You can make them in the laboratory, but they haven't occurred naturally. So I'm more optimistic about this. I guess the other question for Dr. Taylor would be how long is that immunity going to last, though. Is it going to be annual, two years, five years, 10 years? Because being one who's eligible for the adult RSV vaccine, without getting too personal, I want to know the answer to that.
Albert A. Rizzo, MD:
We're in the same boat.
Barbara Taylor, MD, MS:
That is a great question. I would echo that predictions are always very dangerous, but I am optimistic that RSV is less likely to change and have escape mutations than COVID. But I also very much recall the descriptions of the potential mutability of SARS-CoV-2 at the beginning of the COVID pandemic. "Oh, it's not as bad as flu and things like that." And now, we're in this mass, awash with variants of various letters and numbers and shapes and sizes, but I do think it's less likely.
I also think that in the case of RSV, we have really pretty decent whole genome sequence surveillance that we will be able to see if escape mutations arise. It would be a challenge, because all of our current vaccines and the monoclonal antibodies are targeted to the pre-fusion F and to specific sequences there, and it would be a challenge.
The question of how long the RSV vaccine is going to last is a very good one, and I think the safest answer for that is we don't know yet. We've seen this vaccine in adults through two seasons, but our seasons are also atypical because of the disruption, the 2020, and 2021 disruption of the no RSV, no flu season. And so I think time will tell with how frequently we get to need the RSV vaccine. Right now, it's just a single-dose recommendation.
Albert A. Rizzo, MD:
Well, thank you both. You've covered a lot of science behind these vaccines. A very exciting year for RSV. You've also covered some of the hurdles and logistics that hospitals and practices and patients have to deal with. So hopefully things will get better as we go along. Thank you both for your time today.
Barbara Taylor, MD, MS:
Thank you so much for having us.
Leonard R. Krilov, MD:
Yes, thank you.