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The CDC’s Advisory Committee on Immunization Practices (ACIP) recommended an RSV vaccine for pregnant people that would protect infants against the respiratory virus. The vaccine is recommended for use in weeks 32 through 36 of pregnancy, using seasonal administration during September through January.
Sandra Fryhofer, MD, the AMA’s immediate past board chair and liaison to ACIP, joins to discuss the recommendation and its nuances, plus how this maternal RSV vaccine compares to the new monoclonal antibody RSV shot. AMA Chief Experience Officer Todd Unger hosts.
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- Sandra Fryhofer, MD, immediate past board chair, AMA; and AMA liaison, Advisory Committee on Immunization Practices (ACIP)
Unger: Hello and welcome to the AMA Update video and podcast. Today, we're talking about the RSV vaccine that's given during pregnancy and the new recommendations voted on just last week by ACIP, the CDC's Advisory Committee on Immunization Practices. And back with us today to share all those details and more is our AMA ACIP liaison and the AMA's immediate past board chair Dr. Sandra Fryhofer. I'm Todd Unger, AMA's chief experience officer in Chicago. Dr. Fryhofer, thanks so much for joining us again. It works out really well to have you go straight from the meeting, and then here to talk to physicians about what they need to know.
Dr. Fryhofer: Yes, it is very convenient, Todd. And again, thank you. Thanks for having me back again. And with flu and RSV season already beginning in some parts of the country, the timing of these new recommendations and having this new protective vaccine available could not be better.
Unger: Well, before we get into the details, let's start with what's the big takeaway from last week's meeting?
Dr. Fryhofer: The discussions at this meeting were thoughtful, provocative and somewhat complicated. All available studies and evidence were considered and reviewed, and in context of last year's tripledemic of COVID, flu and RSV. That said, ACIP had an all day emergency meeting on September 22, and recommends with this specific language a dose of maternal RSV vaccine for pregnant people during 32 through 36 weeks of gestation, using seasonal administration to prevent lower respiratory tract infection in infants. And the specific wording in this recommendation is loaded with nuances.
Unger: Well, that word nuances has definitely piqued my curiosity. It's a tough word in today's environment. Why don't we talk a little bit more about what those nuances are.
Dr. Fryhofer: So there are two RSV vaccines now on the market. One by Pfizer called ABRYSVO and the other by GSK called Arexvy and both are FDA approved for those 60 and older and recommended by ACIP in this older age group under shared clinical decision making, which means the patient and their physician have to discuss and decide. But currently, only Pfizer's RSV vaccine version, ABRYSVO, is FDA approved for this younger age group, for pregnant people and only at 32 to 36 weeks of pregnancy. GSK's Arexvy is not, but the open language in the ACIP recommendation does allow for other RSV vaccine options to be included if or when they're approved by FDA.
Unger: Dr. Fryhofer, can you briefly explain how the two vaccines are different? So either one of those RSV vaccines can be given to adults 60 and older, but only one of them is FDA approved for pregnant people. Is that right?
Dr. Fryhofer: Right, right. So only ABRYSVO the one that does not contain the adjuvant, is FDA approved for pregnant people. At least for now both vaccines are RSV pre-F vaccines. Which means they're based on the RSV fusion protein, RSV-F stabilized in a prefusion conformation. But their vaccine platforms are different, and they're made by different companies.
The one by GSK, Arexvy contains an adjuvant, the same adjuvant that's in GSK's recombinant shingles vaccine Shingrix. The other vaccine, ABRYSVO does not contain an adjuvant, but is bivalent, meaning it protects against two different RSV strains, RSV-A and RSV-B. FDA's most recent full licensing approval on August 21 for maternal RSV vaccination only applies to ABRYSVO, the one without the adjuvant.
Unger: Now you mentioned up front, this is good timing, because we're about to approach the fall season. When does RSV season typically start, and how long does it last?
Dr. Fryhofer: Well, the RSV season usually lasts around four to five months, and RSV infections just like flu are usually seasonal, starting in the fall, peaking in winter. The typical RSV season is from October through March, however some parts of the country are experiencing RSV outbreaks now. RSV activity is already increasing in the southeastern United States and Alaska, as well as in jurisdictions with tropical climates including parts of Florida, Puerto Rico, the U.S. Virgin Islands, Hawaii, Guam and the U.S. affiliated Pacific Islands, RSV seasonality can often be different.
Unger: You know what's really interesting about this situation is that it's the pregnant person and not the baby that's getting the vaccine to protect the baby. Talk to us a little bit more about that.
Dr. Fryhofer: Well, as you said, the goal of this recommendation is to prevent RSV in little babies and the concept is give the vaccine during pregnancy so mom's protective antibodies can be passed on to baby, protecting baby during the first few months of life at a time in which these babies are so vulnerable. This is passive immunity. Maternal passive protective antibodies will not hang around indefinitely. Protection from maternal vaccination may begin to wane after three or more months, so timing of maternal vaccination matters.
Unger: So is that the reason for, quote, the seasonal administration that you mentioned?
Dr. Fryhofer: Yes, and again, another nuance in this recommendation. The recommendation says seasonal administration of maternal RSV vaccine. It's not a year round recommendation. Little babies need those protective antibodies during RSV season, which is typically October through March. So timing of maternal vaccination matters, and that's why maternal RSV vaccination is recommended for those who will be at 32 to 36 weeks of pregnancy during the months of September through January. That means the infants of mothers vaccinated from September through January would probably be born during RSV season, which for most parts of the country is October through March. But there is flexibility on timing of maternal dosing in those jurisdictions I mentioned in which RSV season is different.
Now this means mothers of most infants born outside of RSV season, those born in April through September, would not have been vaccinated. However a dose of the new monoclonal antibody nirsevimab can be given to those babies to provide passive immunization.
Unger: Dr. Fryhofer, what do we know about how well the maternal RSV vaccination works?
Dr. Fryhofer: Maternal RSV vaccination can be extremely protective for babies. FDA reviewed a study of 3,500 individuals who were received the vaccine when they were 32 to 36 weeks pregnant. Giving the mom a dose of RSV vaccine at this time during pregnancy reduced risk of their babies getting RSV lower respiratory tract infection by nearly 35%. The baby's risk of having severe RSV infection was reduced even more. Maternal vaccination reduced risk of the infant having severe RSV by more than 90% in their first three months of life, and by more than 76% overall in the first six months after the baby was born.
And remember, RSV can kill little babies. RSV is the most common cause of hospitalization in infants in the United States. Just about every child would have had it by the time they hit two years old. RSV kills between 100 and 300 children under the age of five in the U.S. each year. Most infants, 68%, are infected in their very first year of life, and 79% of children less than two years old who get RSV had no underlying medical conditions. This means all young infants are at risk of RSV.
Unger: So Dr. Fryhofer, how does this maternal RSV protection compare to a shot of the new monoclonal antibody? I know we talked about the monoclonal antibody in a previous AMA Update, but can you give us a refresher?
Dr. Fryhofer: The RSV vaccine is a shot given to pregnant people. The monoclonal antibody is a shot given to babies. There are no head to head studies comparing them. Nirsevimab is a long-acting monoclonal antibody sold under the brand name Beyfortus. And it's a single shot given to the baby and its effectiveness lasts for about 150 days. That's about five months.
ACIP voted on August three to recommend a dose of nirsevimab to all babies under eight months old entering their first RSV season. ACIP also recommended a protective dose in their second RSV season for older babies, those 8 to 19 months old who remained at risk of severe RSV infection. For infants born during or those entering their very first RSV season, nirsevimab was 79% effective against RSV medically attended lower respiratory tract illness, and 80% effective at preventing hospitalization and no specific safety concerns were identified.
Unger: Speaking of safety, what do we know about the side effects and safety of maternal RSV vaccination?
Dr. Fryhofer: Well, the expected side effects include fatigue, headache, muscle aches and joint aches in the mom. The big safety concern is a possible increase in preterm births linked to vaccination, and here's why. There was a numerical imbalance in preterm birth between Abrysvo recipients and those who received placebo. And in the studies submitted to FDA pregnant persons at increased risk of preterm birth were actually included from the trial. More data is needed to determine if this increased risk of preterm birth is real, but giving the vaccine late in pregnancy at 32 to 36 weeks reduces the potential risk of preterm birth and its potential complications.
Now there was also a preterm birth signal in studies of the other RSV vaccine, GSK's maternal vaccine candidate, not yet FDA approved in this age group, which adds to this concern. An imbalance was also seen in the percent of pregnant patients who suffered preeclampsia, and FDA is now requiring post-marketing studies to take a closer look at preterm births, and also to look for any possible link between hypertensive disorders of pregnancy, like the risk of preeclampsia. There were also more babies with low birth weight and jaundice in the pregnant people who received ABRYSVO, and all of these issues will require closer surveillance as the vaccine is distributed more widely.
Unger: We'll keep our eye on that. Dr. Fryhofer, one of the things we've talked about in the past is GBS. Can you tell us a little bit more about the risk of GBS?
Dr. Fryhofer: No cases of GBS or any other demyelinating events were reported in trials among pregnant people, but a possible safety concern for GBS, that's Guillain-Barre syndrome, did come up in studies given the RSV vaccines to older patients. But understand risk of Guillain-Barre increases with age and the background rate of GBS in pregnant people is much lower than among older adults. And FDA's already requiring post-marketing surveillance for GBS for both manufacturers. That decision was made when FDA licensed the two RSV vaccines for those 60 and older.
Unger: I don't know if anybody's asked this question, but should babies get double protection with both an RSV vaccine shot that's given to the mom, and a monoclonal antibody shot for the baby during RSV season?
Dr. Fryhofer: Well, probably not, and that was discussed in detail at the meeting. After maternal RSV vaccination it takes 14 days to build up protective antibodies. So babies born at least 14 days after maternal vaccination should have enough antibodies passed on to them to protect them. But if the baby's born before that 14 day window, they may not receive enough of mom's protective antibodies. In that case, nirsevimab can be considered if the physician decides the potential incremental benefit is warranted.
Consideration of double protection would also include cases in which the pregnant person may not be able to mount an adequate immune response to vaccination, like those with immunocompromising conditions. The need for double protection could also apply to infants with substantial increased risk for severe RSV, and this was would include babies with hemodynamically significant congenital heart disease, ICU admission and for babies requiring oxygen at discharge. A dose of nirsevimab can be administered October through March, which is the typical RSV season.
Unger: What are the relative risks and benefits of maternal vaccination versus giving the baby a dose of monoclonal antibody?
Dr. Fryhofer: Well, that's a great question. Maternal vaccination avoids having to give the baby an injection. The mom gets it instead. Also maternal vaccination may be more resistant to any virus mutation. Maternal vaccination provides protection immediately for the baby after birth. However protection from RSV may be reduced if the mom produces fewer antibodies, which means fewer antibodies would then be passed on to baby, or if the infant was born too soon after maternal vaccination. And of course, we talked about the potential risk of preterm birth linked to maternal vaccination.
For passive immunization with nirsevimab, studies show its protective antibodies may wane more slowly. It can provide antibodies directly if the infant receives less maternal antibodies. One potential risk right now is limited availability of nirsevimab during the 2023/2024 RSV season. So some babies who could really benefit from it may not have access to it at this time.
Unger: Dr. Fryhofer, of course, there are other vaccines in this fall season. What about co-administration of the maternal RSV vaccine with other vaccines?
Dr. Fryhofer: RSV vaccines can be co-administered with other vaccines. So pregnant people could potentially be eligible to receive RSV, Tdap, COVID and flu shots all at the same visits. But one study of co-administration of Tdap and Pfizer's RSV vaccine found reduced immune response to the pertussis components. Now remember, Tdap is recommended at 27 through 36 weeks of pregnancy. So 27 through 36 weeks of pregnancy for Tdap. So you could give Tdap before 32 weeks, and give the RSV vaccine after 32 weeks, so that way you wouldn't have to give them both at the same time.
Unger: One of the things we're talking about now as far as COVID goes, of course, changes around insurance and health equity concerns. Let's talk a little bit about this in particular. What about health equity concerns in babies who are uninsured or underinsured?
Dr. Fryhofer: Well, there's some good news here because both maternal RSV vaccination and nirsevimab were voted by ACIP to be part of VFC, the Vaccines For Children program, and this means both options are available to children without health insurance. And that's very important for access. There are several important health equity concerns, however. We know Black children have higher rates of RSV associated deaths compared to white children. ICU admission rates for Black babies under six months old are 1.2 to 1.6 times higher than for white babies. Another study showed RSV hospitalization rates were 4 to 10 times higher among Alaska Native and American Indian children under two years old as compared to the general population. So having both of these options available on VFC helps ensure access to all babies.
Unger: Dr. Fryhofer, you weren't kidding when you said this was going to be a jam packed session full of really helpful details. Do you have any final thoughts before we close?
Dr. Fryhofer: RSV is the most common cause of hospitalization in infants in the United States. RSV kills between 100 to 300 children under the age of five in the U.S. each year. Most infants are infected in their very first year of life, and just about every child would have had it by the time they hit two years old. All young infants are at risk of RSV. We now have two good options for preventing RSV in little babies. Pregnant people should be aware that they have a choice. They can either receive a dose of maternal RSV vaccine themselves at 32 to 36 weeks of pregnancy or their baby can receive a dose of the long acting monoclonal antibody nirsevimab after delivery. Most infants will not need both. These recommendations are new, and while they're somewhat complicated, they're important and will help save lives.
Unger: Well, Dr. Fryhofer, thank you so much for being here today. As always, so much great information we hear back from physicians out there. It's really important to hear from you. That wraps up today's episode. We'll be back soon with another AMA Update. In the meantime, you can find all our videos and podcasts at ama-assn.org/podcasts. Thanks for joining us today. Please take care.
Disclaimer: The viewpoints expressed in this podcast are those of the participants and/or do not necessarily reflect the views and policies of the AMA.