Boosting our Vaccine Knowledge: Updates, Allergy and Special Populations

Vaccines are a cornerstone of public health, training the immune system to prevent infectious diseases, especially in our most vulnerable patients. In this episode, John Kelso, MD, FAAAAI, reviews recent vaccine developments, including the importance of measles vaccination amid ongoing outbreaks, updates to vaccination schedules, considerations when using vaccines with biologics and evaluation of vaccine allergy. Join us for a practical review of key vaccine updates to help you protect your patients.

 Find out more about the importance of vaccinations across age groups. 

Transcript

Rebecca Saff, MD, PhD, FAAAAI 0:14

Podcast series by the American Academy of Allergy, Asthma & Immunology. I'm your host Rebecca Saff. I'm a board certified allergist and immunologist who always enjoys learning more about our exciting field. Our podcast series will use interviews with thought leaders from the world of allergy and immunology to keep you up to date on new developments and to review core topics. Today we'll be discussing a surprisingly controversial topic these days, vaccines. Vaccines are the most effective way to prevent many infectious diseases. By training our immune system to recognize specific bacteria and viruses that cause disease, they can prevent illness, hospitalization, and death. And they don't not only protect an individual, but protect vulnerable populations by generating immunity within a community, the so-called herd immunity, protecting people with inborn errors of immunity or who are on immunosuppressive medications and are not able to get vaccines. They are a cornerstone of public health and have led to the eradication or near eradication of diseases like smallpox, polio, and measles, saving millions of lives and improving overall health and economic well-being for all of us. For this important discussion, we are pleased to welcome Dr. John Kelso. Dr. Kelso is a clinical professor of pediatrics and internal medicine at University of California, San Diego. He has served on the board of directors for the ABAI as well as the AAA AI. He has a special interest in allergic reactions to vaccines and has led an effort to allow patients with egg allergy to safely receive influenza vaccines. Dr. Kelso, thank you so much for taking the time to join us today.

John Kelso, MD, FAAAAI 1:33

Sure.

Rebecca Saff, MD, PhD, FAAAAI 1:35

Would you start by telling us a little bit about yourself and maybe something you like to do outside of medicine?

John Kelso, MD, FAAAAI 1:40

Sure. So I'm in practice at uh Scripps Clinic in San Diego, where we see both uh children and adults with a pretty broad range of allergic disease, and where we have a fellowship program. And when I'm not doing medicine, um years ago I used to do triathlon, which I don't do anymore, but um I do still go to the gym every day. And I love to travel. We have uh trips that we're planning coming up to uh Africa and then subsequently to New Zealand. And I'm also trying to improve my Spanish.

Rebecca Saff, MD, PhD, FAAAAI 2:17

Very nice. What was your favorite event in the triathlon?

John Kelso, MD, FAAAAI 2:22

I don't know that there really is a favorite. They all kind of wear wear on you as you go along. There's kind of funny stories that a lot of people say, gosh, if I can just get through the swim, I'll be okay. And uh when people get off the bike, they say they never want to see their bike again and head out on the run. So it kind of uh just just as you go along, you just have to get through it.

Rebecca Saff, MD, PhD, FAAAAI 2:44

And what led to you being interested in vaccines in particular?

John Kelso, MD, FAAAAI 2:49

Well, serendipity, I guess. I had a uh patient years ago who told me that she had had what clearly sounded like an anaphylactic reaction after getting a uh measles, bumps, and rubella vaccine. And she was uh college age. That was at a time when we were uh giving patients MMR vaccines before they went off to college. And it turned out when she was describing to me what had happened during the reaction, when she got to the part about her throat swelling, she said, kind of like what happens when I eat jello. And initially I thought, what? And um, but of course, um now we know, and all I had to do was look it up that there's a fair amount of gelatin in MMR vaccine, and sure enough, we demonstrated that the thing in the vaccine that she was allergic to was in fact the gelatin. And um, so that kind of we published that, and I guess that was kind of my entree into the world of various reactions that people have to vaccines.

Rebecca Saff, MD, PhD, FAAAAI 3:52

Can you remind us what the major types of vaccines are and kind of what the how the immune response is generated differs depending on what type of vaccine they get?

John Kelso, MD, FAAAAI 4:01

So I guess there's a couple ways that we kind of divide vaccines. One is those that are killed, meaning that the it's a virus or bacteria that's been killed in some way, or more often kind of parts of viruses or bacteria that we're immunizing people with. So something that doesn't actually have the ability to replicate, but you still mount an immune response to. And then we do have some what are called live attenuated vaccines, which as the name implies, do have some ability to replicate, and that's part uh an important part of how they generate their immune response, but they've been attenuated so that in a person with normal immunity you get the desired immune response, but the vaccine doesn't have a chance to actually cause disease. And then another way that vaccines might be divided is just how they're administered. Most of them are injected, of course, but we do have some oral vaccines and we have some intranasal vaccines, so but the desired effect is really the same with all of them, which is to generate an immune response, both humoral, in other words, to make antibodies to the immunizing agent, which is what we usually think of, and what we usually measure, like you know, you can get a titer to a lot of these things. But importantly, virtually all vaccines also generate a cellular immune response. And we don't really have any, certainly not in a commercial laboratory, we don't have a way to measure that, but that is also being generated at the same time to the vaccine. So we're generating both humoral and cellular immunity with the typical immune memory, so that of course, when we encounter the the infectious agent in real life, that we already have this immune response ready to fight off the infection, if you will.

Rebecca Saff, MD, PhD, FAAAAI 5:50

So the different vaccines kind of have different effects on the immune system. So, for example, it's varicella needs more of a T cell response, and then you know, Haemophilus needs more of a B cell response, is and there's just no way to know kind of the T cell response that we're generating at this point. Is that right?

John Kelso, MD, FAAAAI 6:06

Correct. There are there are research laboratories. I mean, the I guess the reason we we would expect that there would be those responses just knowing the immunology. And in research laboratories, they can they can measure those cellular immune responses. And they even tried when we were during the uh COVID pandemic, when they were trying to have more sophisticated ways to tell if people were responding to the vaccine. There, there was actually a commercial laboratory that tried to stand up a an assay to see if somebody had made a cellular immune response to the vaccine. But though those things are generally not commercially available. So we we know it's happening. It's important, it's an important part of what happens, the the uh cellular response, but it's not something that's easily measured uh like measuring vaccine titers.

Rebecca Saff, MD, PhD, FAAAAI 6:55

Yeah, much easier to measure a titer than a cellular response.

John Kelso, MD, FAAAAI 6:58

Sure.

Rebecca Saff, MD, PhD, FAAAAI 7:00

And then live vaccines are currently an issue with the biologics that we have because most of them have a concern with giving a live vaccine. Um, for example, in in allergy, things like homolusomab and dupilomab are now administered in young children, which is where some of the live vaccines come. How should we think about that when these kids that need to be on this for food allergy or for atopic dermatitis?

John Kelso, MD, FAAAAI 7:24

So I think the the initial thought there is that the biologic might be immunosuppressive. And I think the reason that we think that is there are biologics that are immunosuppressive. The the ones that kind of came before the ones that we use, particularly ones in rheumatology, the anti-TNF drugs, et cetera. So there are biologics in that category that have some immune suppressive uh activity. And the concern there, I guess, would be two things. One is that if you're immune-suppressed in some way, if you get a killed vaccine, there's not a safety issue, because again, the vaccine can't replicate, but you might not mount an adequate immune response to it because you're immune-suppressed in some way. The other concern, and perhaps the greater concern, at least theoretically, is with these live attenuated vaccines that we were talking about, where in a person with normal immunity, the vaccine replicates in a very limited fashion, but doesn't actually cause disease. But if you're immune-suppressed in some way, that viral replication, even of the attenuated virus, might actually lead to disease caused by the by the vaccine. And so if if a biologic was immunosuppressive in some way, that might be a concern. But when you really look at the biologics that we use in allergy, just looking at the way they work, there's not really a reason to think that they're immunosuppressive. You know, we don't there aren't warnings on them, for example, to screen people for TB before you start them or to get vaccines before you start. There's not the both in terms of how they work and recommendations that are made in how they're used, there's really not a reason to think of them as being immunosuppressive. And and then we also have some limited experience. So even though, for example, the package inserts for most of these things would say, well, don't give the patient a live vaccine, that's only because they didn't study any people in that in that way. But in real life, of course, there have been children who've been on these medications who've gotten their usual childhood vaccines, which include live vaccines like Varicella and MMR, who have tolerated them just fine. And so, with that, the the understanding of how the medications work, as well as this limited clinical experience, both the academy and the college have put out statements that say the consensus opinion is it's actually okay to administer those vaccines to children who are receiving biologics like omalisimab or uh dipulumab that might be given at a time when they would be receiving those live attenuated vaccines on the usual childhood vaccine schedule. The only of one of the biologics that I suppose could have a little more, again, largely theoretical concern might be TESPLEUMAB because it's a little higher upstream, you know, blocking TSLP. Now, whether that it's high far enough upstream that it blocks something that, you know, there's still no requirements there about really concern for it caught causing immunosuppression. But I I I guess in that case there there might be uh slightly more concern. But but for the the OMLISMAB and the uh depiliumab in particular and the MMR and Faricella, the the consensus is that there really is not a safety issue there, and it's much more important to go ahead and vaccinate those children.

Rebecca Saff, MD, PhD, FAAAAI 10:58

Absolutely, not to miss those childhood vaccinations because of the medication they're on.

John Kelso, MD, FAAAAI 11:03

Absolutely.

Rebecca Saff, MD, PhD, FAAAAI 11:05

So switching gears a little bit, measles outbreaks continue to occur in communities throughout the United States. Currently, South Carolina has an outbreak. What do we need to know about these measles outbreaks as allergy immunology physicians?

John Kelso, MD, FAAAAI 11:18

Well, maybe the first thing to know is that they are entirely preventable. They should not be happening. Measles is often cited as the most contagious virus there is. I mean, it's it's it's wildly contagious. You know, one person who has it who's been in a room with some number of other people is very likely to infect a large percentage of those people. But in spite of that, in populations where the vaccination rates are high, and high meaning like 94, 95% of the people have been vaccinated, you don't see that kind of spread. So all these outbreaks are occurring in places where the vaccination rates are lower than that. So the the these events are entirely preventable. And so certainly all children should be vaccinated against measles with the MMR vaccine according to the usual childhood vaccine schedule. Adults who were born prior to 1957 are assumed to have had those diseases and should as children and have lifelong immunity. But if you were born in 1957 or later, you can't be assumed to have had those diseases as a child and you should receive a vaccine. And if you haven't gotten one, you should get one. And then there's special uh considerations around the outbreaks themselves. So if there is an outbreak, part of the containment strategy of that is to go in and vaccinate people in that area to try to get the immunity rates up around the outbreak to try to limit the spread of the outbreak, which sometimes even includes giving people a third dose. So the on the usual childhood vaccine schedule, you get two doses, and that for most people gives you lifelong immunity. But that immunity does wane a little bit over time, and in the setting of an actual outbreak where you might be exposed to somebody with the disease, uh that may not be sufficient. And so sometimes even people who have received their normal vaccines previously will get a third dose at the time of the outbreak to try to contain the outbreak.

Rebecca Saff, MD, PhD, FAAAAI 13:28

Is there any role for titers?

John Kelso, MD, FAAAAI 13:32

You can measure, and they're pretty easily measurable. Um, measles and mumps and rubella titers. For most vaccines, say again, the the titers are kind of the low-hanging fruit because it's pretty easy to measure antibody levels to something. So that's what we do. And there are what are thought to be correlates of protection. So if your titer is at this level, if you have a certain amount of IgG antibody that you have generated to having been vaccinated, that that is likely to protect you from disease. But those again, they're sort of surrogates. That's but you know, the the vaccine does work, and those are the titers that people have seen when it seems to be working properly. But again, there's even kind of exceptions to that, like in the case of an actual outbreak. So in the case of an actual outbreak, you would not want to get a titer to somebody to see if they're sufficiently protected if they would be eligible for a third dose of the MMR. You would just give them the vaccine.

Rebecca Saff, MD, PhD, FAAAAI 14:37

And then I think that it's important to dispel some myths about the measles vaccines. Are there myths that you've heard that people tend to tend to ask you about in clinic that would be important to dispel?

John Kelso, MD, FAAAAI 14:50

Well, the the most important, of course, is that somehow MMR vaccine causes autism, which you know came from a paper from now decades ago by a long discredited author who was getting money from families of children who had autism, and somehow construed this paper to suggest that MMR vaccine caused autism. And subsequent to that, uh probably literally billions of dollars have been spent evaluating that in every way possible, in every kind of very sophisticated long-term epidemiologic studies, and there is absolutely no connection between MMR vaccine and autism. But of course, that led to people being concerned about it. And so, you know, parents they they hear things from all over the place, especially these days. You know, they heard something on TikTok or their neighbor said something, and people seem to give as much credit to that as what their doctor told them. And so they they're hearing a lot of different things from a lot of different sides, and that just creates confusion and and misunderstanding. But importantly, the the suggestion that measles vaccine caused autism wasn't just sort of dismissed out of hand, it was taken seriously, it was studied thoroughly. There's absolutely no connection there. And so so that's the kind of thing, though, that that parents have heard, and that sometimes we have to try to lead them in the right direction.

Rebecca Saff, MD, PhD, FAAAAI 16:23

Absolutely. And interestingly, measles actually, if you get infected with measles, it actually kind of wipes your immunity out and you you lose immunity to things that you were already protected from. Is that right?

John Kelso, MD, FAAAAI 16:35

Correct. So that that um, you know, measles, I've never seen a case of measles. Most of my colleagues haven't, and there's a reason for that. It's was virtually eliminated by by the vaccine. And uh, but there are uh people uh from say the generation prior to mine who did see lots of cases of measles, it's not a benign disease. Uh there are children who die from measles, people uh measles pneumonia, measles encephalitis. This issue that you're describing, where it can, like you said, sort of wipe out your immune system. So, I mean, there are very serious uh deaths, there are very serious consequences for some percentage of children who get measles, and it's absolutely preventable by this very safe vaccine that's been used for decades. So uh there's just no reason for uh the, for example, we've had deaths in children from measles last year in the United States of America, which is really really inexcusable.

Rebecca Saff, MD, PhD, FAAAAI 17:38

So the vaccine schedule that we follow for our children was recently changed pretty significantly. What are the changes that we need to be aware of?

John Kelso, MD, FAAAAI 17:48

Well, what used to be a list of sort of usual childhood vaccines, the the schedule of the diseases that all children were recommended universally to be vaccinated against. The CDC recently reorganized that and they took about a third of the vaccines from that schedule and put them into a group that said that they're recommended only for certain high-risk groups. And they took about a third of them off, another third off the schedule and said they're supposed to be with shared decision making, that you're supposed to have a discussion with the families about whether or not they want to get the vaccine. And this includes vaccines against influenza, for example, or COVID. Uh so there's that that schedule, though, the the reason that those changes were made was really not based on any science. We we have lots of science, we have decades of science that demonstrate that these vaccines are safe and effective and prevent these diseases. So, in reaction to the changes that the CDC has made, virtually every other major healthcare organization, the American Medical Association, the American Academy of Pediatrics, the American Association of Family Practitioners, the American College of Obstetrics and Gynecology, have all rejected those changes, and our their formal recommendation is to not follow the current CDC schedule, but rather to follow the schedules that are promoted by those organizations. So the American Academy of Pediatrics still puts out a vaccine schedule every year. There's one for 2026. It looks an awful lot like the old CDC vaccine schedule before they made those changes because the scientists, infectious disease experts, vaccinologists representing the American Academy of Pediatrics know the science and they're still promoting the appropriate use of these vaccines universally to prevent these diseases. So that again adds to the confusion of what parents and families are supposed to think is the right thing to do. But the right thing to do is to follow the advice of the experts in these groups, professional societies that are saying that these vaccines should still be universally administered. So trust your pediatrician, trust your family practice doctor, trust your internal medicine doctor, because they will tell you, and their professional organizations will tell you that it is still appropriate for patients to get these vaccines.

Rebecca Saff, MD, PhD, FAAAAI 20:36

You mentioned the flu being removed from the childhood vaccination schedule. Could you tell us some of the data supporting the use of the flu vaccine, particularly in children and what it can prevent?

John Kelso, MD, FAAAAI 20:48

Sure. So again, loads of data, lots of studies that demonstrate that getting a flu shot either completely prevents you from getting influenza, or if you do get influenza, you would have a much milder case of it. That's something that a lot of times vaccine skeptics point to and say, Well, look, I got a this person got a COVID vaccine and they still got COVID. There you go. That just proves that the vaccine doesn't work. Well, maybe they did get COVID, but they didn't end up in the hospital and they didn't die from it. So the vaccines, particularly for things like influenza, the vaccine or the virus itself changes every year, so they have to try to keep up with it. They have to make the decision about what they're going to put in the flu shot before the actual flu season arrives. And sometimes the match isn't perfect. But even in the years where the influenza vaccine doesn't perfectly match the viruses that are actually circulating, it still is effective. So in terms of decreasing uh hospitalizations and deaths from influenza, uh, I just looked this up this morning. So As of now, for the this current influenza season, so starting last fall up through now, there have been 18 million cases of influenza, 230,000 hospitalizations, 9,300 deaths from influenza in patients of all ages. That includes 17 deaths in children, 90% of whom were not vaccinated. So children are dying now from influenza for having not been vaccinated. And so there's a real impact, a real live impact of this right now and in every influenza season from not being vaccinated. So the majority of those hospitalizations and deaths could have been prevented had those patients received a flu shot. So that's why it just seems baffling to have the influenza vaccine suddenly be some sort of optional, you know, to not have it be universally recommended. Well, why would you not get this benign vaccine if it's going to prevent you from having these potentially serious or even deadly consequences of getting influenza? So the data is strong. And people need their flu shots.

Rebecca Saff, MD, PhD, FAAAAI 23:28

And then these days it's probably the numbers are higher, but we're not seeing it because people can test at home or they don't bother to test. So the people that were actually in that group that got vaccinated stayed home because they didn't have a severe case and were able to kind of get through it. We're probably not even measuring those people at this point.

John Kelso, MD, FAAAAI 23:47

Correct. The single best thing you can do to try to prevent having influenza or a severe outcome from influenza is to be vaccinated every year.

Rebecca Saff, MD, PhD, FAAAAI 23:57

Now, are there special populations that we should be aware of that really need specific vaccines?

John Kelso, MD, FAAAAI 24:04

So there are some of those. Maybe the one one of the examples that uh sometimes come shows up in the allergy clinic is uh patients who are asplenic, for example. So, of course, if you don't have a spleen, you're more susceptible to infection with encapsulated organisms. So people who don't have a spleen uh need to be vaccinated against uh hemophilus influenza type B, pneumococcus, meningococcus, even when they might not otherwise be in age groups or populations for which those vaccines would be uh indicated, because they have a special propensity to uh infection with those organisms. So that's one example. But the uh the vaccine tables are really a wealth of information. So again, we're talking about the vaccine tables from the AAP and the AAFP, etc. Uh those those vaccine schedules, in addition to saying you should get this vaccine at this age, then just below that there's another table, not divided by age, but divided by medical condition. So patients who don't have a spleen, patients who are immunosuppressed, patients who are have HIV, patients who, you know, there are different categories of patients who may be susceptible to certain infections for which particular vaccines are indicated, and um all very carefully laid out in the in a in a table that's pretty easy to follow. So when a patient shows up, that's what I do. If a patient, for example, who who's asplenic shows up, I just get out that table and I go down the list. Okay, somebody who doesn't have a spleen needs to get these vaccines. Have they had them or not? What interval are they supposed to get them at? Are they are they due for another one? Uh and just to make sure that they they've received the full complement of vaccines to protect them as best we can from particular infections that they would be susceptible.

Rebecca Saff, MD, PhD, FAAAAI 25:59

And as allergists, are there concerns about allergic reactions to vaccines that we need to be aware of? And particularly, I'd love to hear a little bit about kind of the history of the flu vaccine and egg allergy and kind of how we've moved now been able to move beyond that and now vaccinate all of our patients with egg allergy with the flu vaccine.

John Kelso, MD, FAAAAI 26:19

So uh all almost all influenza vaccines are literally grown in eggs. I mean, they're there are pictures of of the factories where they make influenza vaccine and they're pushing around carts of eggs. And there is a little bit of egg protein, usually measured as ovalbumin, in the vaccine. And so for decades it was assumed that if you were allergic to eggs, obviously we wouldn't want to inject you with ovalbumin because clearly you would have an allergic reaction. But somewhere along the line, people started to think, well, wait a minute, but we're leaving these children susceptible to influenza. It's not benign to go unvaccinated. And starting to find out, well, what happens if you give egg allergic children the vaccine? And we went through all kinds of iterations of that. We were skin testing with the vaccine and giving it in graded doses and sort of creeping up on the answer to that. But the answer is no matter how exquisitely allergic to egg you are, you know, a kid who just looks at a scrambled egg and has anaphylaxis, you know, no matter how allergic you are, nobody has a reaction to the influenza vaccine. So the question is, well, why why is that? You know, we're we're injecting them with ovalbumin. They're really allergic to eggs. Why are they not reacting? Because it's just not enough ovalbumin. It's like you know, 0.1 uh micrograms of ovumin in there. It's it's just not enough ovumin to cause a reaction, no matter how egg allergic you are. And so over a period of time with more and more data sort of you know lightening up on saying it's okay to give influenza vaccines, uh, both it turns out for both the injected and the intranasal vaccines the same thing, that that we were not seeing any reactions to those, then the current recommendation became obvious that you were not at any increased risk, which then raised the question: well, why do we ask people the question in the first place? Why is it on the screening form? If it doesn't matter, if we're going to give the kid the vaccine anyway, why are we asking them if they're allergic to eggs? And so the American Academy of Pediatrics and now the the CDC, the advisory committee on immunization practices, have said you don't need to ask the question. It is not necessary to inquire if somebody's allergic to eggs before giving them an influenza vaccine. So that was kind of the evolution of that. And and um I think that really has largely caught on now that people are starting to realize that's just really not an issue, and uh and administering the vaccines, and of course, that allows us to protect that many more patients from influenza.

Rebecca Saff, MD, PhD, FAAAAI 29:01

Are there vaccines with high enough levels of egg in it that we have to be concerned?

John Kelso, MD, FAAAAI 29:06

Well, the only other one that had any amount of egg in it that we were kind of concerned about was yellow fever vaccine, and it has slightly higher amounts of, you know, a few micrograms of ovalbumin in it. And then uh, and of course, since that there are many fewer people who get yellow fever vaccine than influenza vaccine. You know, you get it only for travel, or if you live in certain countries, these days you only get it once in a lifetime. So there are fewer patients to study who had egg allergy who needed yellow fever vaccine. But in parts of the world where yellow fever does is uh an issue and where people are routinely vaccinated or where there are outbreaks where they're vaccinating large numbers of patients, they now have, in fact, collected data on truly egg allergic children who have gotten yellow fever vaccine and also done so uneventfully. So the yellow fever vaccine is also now not an issue in terms of egg allergy. And since that was the only other vaccine that we had any concern about, it's it's really not necessary to inquire about egg allergy prior to the administration of any vaccine.

Rebecca Saff, MD, PhD, FAAAAI 30:14

Are there you mentioned gelatin earlier? Um there other things that we need to be aware of in terms of ingredients and vaccines that can cause allergic reactions that we should ask patients about.

John Kelso, MD, FAAAAI 30:25

Gelatin really is the only one. So they're uh and again it has to do with the amount. The vaccines that have gelatin in them, like uh MMR and varicella, for example, have milligram quantities, like 12 milligrams or 14 milligrams. There's a big slug of gelatin in that vaccine. And if you happen to be one of the rare people who is allergic to gelatin and you get that much gelatin injected, then you might in fact have uh anaphylactic reaction to the vaccine. So that that that one is a real deal. That's also supported by the fact that there's other examples of gelatin allergic patients responding to gelatin-containing medical products. So in the US we don't use it, but in other parts of the world they use sort of liquid gelatin, if you will, as a volume expander. And there are plenty of examples of anaphylaxis to that. Even in the US, there are uh surgical sponges that have gelatin in them. That when they put them in, somebody who's allergic to gelatin has had an anaphylactic reaction. So if you're if you're gelatin allergic and you're exposed to a large enough amount of gelatin, you very definitely can have anaphylaxis from that. And there is enough in the in those vaccines to cause it. But gelatin allergy itself is really quite rare. There's been other exceedingly rare examples where some vaccine, immediate vaccine reaction was tied to some allergy. For example, there were a handful of patients who got DPT shots or TDAP shots, who were exquisitely milk allergic, who appeared to have reactions to the vaccine. And even though the vaccine doesn't say it contains milk protein per se, it's made in cas amino acids, which is amino acids from digested casein. And I guess there was a little residual leftover milk protein in that batch and caused some reactions. But we didn't respond to that by saying milk allergic children shouldn't get their TDAP vaccine. Those are really rare examples. And then sometimes there's concern about patients who have allergic contact dermatitis to things that are used in the in a vaccine, like neomycin, for example. There are tiny amounts of neomycin in certain vaccines, and even but even if you were had allergic contact dermatitis, you were patch test, clearly patch test positive to that, getting that little bit in your vaccine either causes no reaction at all or it causes a little nodule that goes away quickly. So even people who have delayed type hypersensitivity reactions to these vaccine constituents, that's really not a reason not to vaccinate them. So really the only thing that you could be allergic to where we would say, well, we better be a little cautious or do some investigation ahead of time before you get a vaccine is gelatin. And even in that case, the solution to that isn't to say, sorry, you can't get these vaccines, it's to say, well, we can try to give it to you in graded doses. We'll we'll try to get it into you somehow, even though you're allergic to the gelatin. So that really is the only one ahead of time that would be an issue. Now, if somebody's actually had a reaction, not to a constituent ahead of time, but to the vaccination itself, then we might want to look and see, well, you know, do a skin test with the vaccine or see what was in there that they might have reacted to in these rare circumstances. But for the most part, other than this rare issue with the gelatin, there really are not things that allergies that we need to be screening people for prior to giving them their vaccines.

Rebecca Saff, MD, PhD, FAAAAI 33:55

We've certainly had a number of people that have had reactions to vaccines. We skin test them, we give them a graded challenge, and they're able to tolerate it. And so something about that administration caused a reaction, but they're able to tolerate it down the line. So always worth kind of re-evaluating.

John Kelso, MD, FAAAAI 34:10

Absolutely. Because again, whatever the situation is, if you're concerned about giving a vaccine for whatever reason, and it might seem like the prudent or conservative thing to do, to say, well, gosh, the patient might have a reaction, we better not give them the vaccine. Remember that you're weighing whatever risk there is of getting the vaccine, not against nothing, but you're weighing it against the risk of not being vaccinated and leaving the patient susceptible to a vaccine-preventable disease. And in most cases, leaving the patient susceptible to that disease poses a far greater risk than whatever risk the vaccine would pose.

Rebecca Saff, MD, PhD, FAAAAI 34:48

Absolutely. And so now we're changing from pneumovax to PREVNAR is the kind of vaccine we use for strep pneumo. Um, who should receive the PREVNAR vaccine versus the pneumovax vaccine?

John Kelso, MD, FAAAAI 35:01

So the evolution of that, of course, has been that uh when they first came out with the pneumavax, which has 23 different serotypes of the pneumococcus bacteria, which of course is a has a polysaccharide on the outside. And it's hard for our immune system to respond to polysaccharides. Our immune system is geared up to deal with protein. I mean, you know, the antibody molecules, the thing that fits that sticks to an antibody molecule is a peptide, you know, is a protein, it's state they're sticking to protein. When you make a T cell response to something, you're responding to a peptide fragment. So the whole deal is geared up to deal with protein. So dealing with a polysaccharide, which presumably the bacteria did to try to outsmart our immune system, putting this polysaccharide on the outside made it hard for anybody to mount a very robust or long-lasting response to the pneumococcus bacteria. So somebody had the bright idea to say, well, let's take those polysaccharides and conjugate them or stick them to a protein and see if that works better. And sure enough, it does work better. You can sort of fake out your immune system. The antibodies that you generate against the polysaccharide when it's stuck to the protein, you generate a much more robust and long-lasting immune response. And so that's when they came out with PREVNAR, which was initially Prevenar 7, and then PREVNAR 13, and then there was a 15, which actually had some other name. And then there was a Prevenar-20. So they just kept conjugating more and more of the 23 serotypes that were in the PHUMAVAX. So the most recent iteration of that is uh uh 21. So the CAP vaxive, so that's the the latest entrant into this vaccine, these conjugated vaccines. Interestingly, and I think importantly, they didn't just add one more of the 20 off that list of 23 that they were originally working with. So CAP vaxive, the particular serotypes that are in there are there's some of them that overlap with what's in uh PREVNAR 20, but there's also some that that were never in any of the other uh pneumococcal vaccines because the particular strains of pneumococcus that actually cause disease have changed over time. And so now this new vaccine includes the CAP vactivity, they're all conjugated. There's 21 serotypes in there, but it's not uh complete overlap with what was in pneumovax or or PREVNAR20. It's kind of a geared at having you vaccinated against what's what's currently circulating and actually causing disease. So everybody is is supposed to get a uh uh at age 50 to get a conjugated uh pneumococcal vaccine, which could still either be PREVNAR20 or this new CAP active. And uh children, of course, get a uh a series of these on the usual childhood uh vaccination schedule as well.

Rebecca Saff, MD, PhD, FAAAAI 37:59

So for the the PREVNAR vaccines, are we needing boosters? So oftentimes with our asthma patients, we'll actually vaccinate them ahead of time before they would typically for the average age. Do they need boosters over time, or do we think that these are good enough vaccines that they really get long-term immunity from it?

John Kelso, MD, FAAAAI 38:16

So with the conjugated vaccines, we really do think that those that you just get those once and that that provides long-lasting immunity. Another problem with the polysaccharide vaccine, pure polysaccharide vaccine, was that the response again tended to wane over a fairly short period of time. And then you think, well, that's okay, just give them another one. Well, you know, we'll just give them another pneumovax, we'll boost them. But it turns out for some reason with polysaccharide vaccines, they don't boost very well. So if you've gotten a pneumovax and then it's five years later and you get another one, you might not make a very good response to it the second time around. So you only kind of had one shot at it. But whereas with the conjugated vaccines, you really are generating a more robust and long-lasting response. And for most people, you just get one. There's some exceptions where, as we're kind of transitioning, where some people may, let's say somebody only got Prevnar 13 in the past, or the only vaccine they got in the past was the PneumaVax. So you you might give somebody one of the newer vaccines to sort of catch them up. That's not necessarily a booster per se. It's you're just trying to get them up to speed with getting the most conjugated serotypes in them that you can. But once you get that, the assumption is that you don't need boosters after that.

Rebecca Saff, MD, PhD, FAAAAI 39:30

So we've used Pneumavax for many years as our a way to evaluate antibody responses in patients who were concerned about immune deficiency. As prevnar 20 and 21 have been available, PNUVAX has become less and less available. Um, if PNUVAX isn't available in these patients, how should we think about evaluating them with these newer vaccines?

John Kelso, MD, FAAAAI 39:51

Yeah, that has been uh an issue, and that kind of gets back to this business with the where it's harder to make immune responses to polysaccharide things, right? So when we're evaluating people's antibody responses, we've typically looked to see can you make antibodies against protein antigen, so measuring you know, tetanus and diphtheria titers, and can you make antibodies against polysaccharides, which would mean if you'd already had a pneumavax, did you did you make a response to it? And if not, we would get blood, give them a pneumavax, a month later, draw another blood sample and see of these 23 serotypes, how many of them did you make an immune response to? And nope, nobody makes a response to all of them, but if you made it to a certain percentage at a certain level, we would say, well, you you make a good response to polysaccharide antigens. And then, as you're correct, so as they've included more and more of these conjugated more and more of these serotypes, if you get a post-numovax titer on somebody, and they've already received a conjugated version of that same thing, you're not really evaluating their response to the polysaccharide because it was conjugated to a protein, so that's kind of not fair. For a while, it there were still between it when it was prepared 20 and PNUX with the 23, there was actually one that didn't overlap. So there were still four purely polysaccharide serotypes that were in the PNUVAX that you could assess people's response to. But because these conjugated vaccines are so effective, and because they now cover such a broad array of the of the serotypes, they're almost certainly going to phase out PNUVAX because there's not really a reason to give somebody a PNUVAX anymore. But then that takes away our tool that we were using to assess these polysaccharide responses. So in the time that we still have it available, it can be used because again, there there's there are some serotypes that are present in PNUVAX that are not present in Reven R20 or CAFAX. So you still have some, as long as it's available, we can still use that as a way to assess response to polysaccharides. Once it goes away, then our kind of fallback or thing that we might have to go to is uh looking at response to another purely polysaccharide vaccine, which is the injectable typhoid vaccine. So that's typically only used for travel, but it is a pure polysaccharide vaccine. It's as far as I know, there's only one place to get the titers measured, and that's at the Medical College of Wisconsin. But you can go online at the Medical College of Wisconsin, and uh there's a form that you can download online to send pre- and post typhoid vaccine titers to their laboratory, and they will tell you whether or not the patient made a response to that polysaccharide vaccine. So we'll we'll have that available. And we we also can use that. The other time that's sometimes used is in patients who are already on antibody replacement therapy. So you you inherit somebody who's on been on IVIG, and when you look back at the record, it's not clear to you that they needed to be on it in the first place. And so one option would be stop it and see how they do. But if you kind of would like to know, well, does this person really make antibody responses or not? Since typhoid is not routinely administered in the United States, the donor pool for the IVIG has very little typhoid vaccine in it. So even somebody who's already on antibody replacement, who would already have somebody else's antibodies to anything else we might immunize them against, we can get we can give do the pre and post-typhoid vaccine titers as an assessment of their ability to make functional antibody against polysaccharides, even though they're on antibody replacement. So that's another way that we can use that uh typhoid. And it definitely specifically has to be the injectable typhoid vaccine, not the oral typhoid.

Rebecca Saff, MD, PhD, FAAAAI 43:50

So is the the typhoid vaccine as readily available as you know, pneumavax used to be?

John Kelso, MD, FAAAAI 43:57

Well, we do travel clinics, so I I guess we have the luxury of always having it in our refrigerator, but I I I think it is pretty easily available. It's not like yellow fever vaccine where you have to be certified to be a yellow fever vaccine provider. I it uh almost anybody would be able to get their hands on the typhoid vaccine.

Rebecca Saff, MD, PhD, FAAAAI 44:18

Right. And then RSV continues to be a concern in both infants and the elderly. Um, what are the RSV RSV vaccines available and who should receive them, particularly in those age groups?

John Kelso, MD, FAAAAI 44:30

So there's the the uh main issue here in terms of children is having RSV, which can be a very serious respiratory uh infection, in uh in infancy. So in their first or second RSV season, which we usually think of as being kind of October through March. So there's a couple ways to protect the babies at that very early age. One is for their mom to receive the RSV vaccine so that she can generate maternal antibodies that can be transferred to the baby, or for the babies uh not to give them vaccine, but to give them RSV antibodies. So a monoclonal antibody that is against RSV. So the recommendation is that uh all children should, if they're either their mom should be vaccinated so that she can give them antibodies passively, or that the baby should get these passive antibodies to protect them against RSV. And like a lot of infections, people at either end of the age spectrum are at risk, where in the case of babies, your immune system sort of hasn't fully developed yet. And as you get to be about my age, your immune system starts to wane and you need a little extra help. And so that that's another time when uh RSV is uh an issue is in older adults. And so uh the current recommendation is everybody over age 75 should should get an RSV vaccine, and people over age 50 who have any additional risk for respiratory infections, which includes patients with asthma. So all patients with asthma after age 50 should get an RSV vaccine to uh because they're at increased risk for RSV pneumonia, and there's there's three uh RSV vaccines that are that are available for adults.

Rebecca Saff, MD, PhD, FAAAAI 46:22

And do they need boosters at any point for these RSV vaccines in the adults?

John Kelso, MD, FAAAAI 46:26

Uh the current recommendation doesn't say anything about boosters, but that's something that uh often with with vaccines, the what needs to be followed is what happens to people over time. Does not only do the titers wane, but does the protection wane? Uh do people, after a certain number of years, after getting an RSV vaccine, do people start getting RSV disease again? And in that case, at some point in the future, a booster might be recommended, but currently uh it's just a single vaccine.

Rebecca Saff, MD, PhD, FAAAAI 46:59

So vaccines are such an amazing tool. Are there vaccines that are currently being studied and maybe ready for broad administration in the population over the next five years?

John Kelso, MD, FAAAAI 47:10

So the ones that I know of that are sort of in the uh pipeline, one is a vaccine that would cover both COVID and influenza in the same shot. And the appeal of that is that as we describe the influenza vaccine changes from year to year. And as we certainly have learned that COVID does exactly the same thing, the virus changes over time, and so they have to kind of update the vaccine to match the currently circulating virus. And since they're both uh things that you would likely be vaccinated against once a year, it makes lots of sense to just combine them in the same vaccine and get vaccinated against both diseases with one vaccine. So there that's uh in the pipeline. And then something else that people have been working on for quite some time is what's called a universal influenza vaccine. So the the thing that changes on the influenza virus every year are sort of the most external parts of the virus. You know, so we have these things that are, you know, H1N, whatever. So those are those refer to things that are on the outside of the influenza virus that change. But there are other parts of the influenza virus that that don't change from year to year that are quite stable. And if you could somehow generate an immune response to those parts of the virus, then you could have an influenza vaccine that would be more effective and more long-lasting. And that for whatever reason has been termed a universal influenza vaccine, I guess because it would cover all types of influenza, uh, but but also would be long more effective and longer lasting. So that's also something people are are working on.

Rebecca Saff, MD, PhD, FAAAAI 48:47

That'd be great to only be able to have to get one flu vaccine that would cover us for many years.

John Kelso, MD, FAAAAI 48:52

Yes.

Rebecca Saff, MD, PhD, FAAAAI 48:53

Versus these boosters every year. Great. Well, this was fantastic. We've covered a lot of different things about vaccines. Is there anything you want to kind of add as a vaccinologist or um some take-home points that you really want to make sure that people remember?

John Kelso, MD, FAAAAI 49:09

Well, I think I think it's especially important for us as allergists, uh, immunologists, uh, even of those of us who are small eye immunologists. That was a uh John John Uniger, um, who was head of the ABAI when I was on the board and was a dear friend from uh a mentor of mine during my fellowship. He used to refer to some allergists as big-eye immunologists. So, you know, we all know a little more about immunology than your regular doctor, but most of us don't really practice immunology per se. But all of us have enough immunology in our expertise that we really should be strong advocates for vaccination. Because as we've discussed, these are important tools, perhaps the greatest public health achievement of all time. The uh, as I said, I've I've never seen a case of measles, I've never seen polio, and the reason for that is that of vaccination. I mean, people the those used to cause, just like we were talking about with influenza, hundreds of thousands of hospitalizations, thousands of deaths every year. Uh, that can really all be prevented, even in my lifetime. If if you ask pediatricians today if they've ever seen a child with H-flu meningitis or or sepsis or epiglottitis, they read about it in the textbook someplace, but they have, or I'm sure they saw it online. They didn't read the textbook, but you know, they've they've they've heard about it, but they've never seen one. Well, I pediatricians in my generation have seen many children die from those diseases. And that just absolutely doesn't happen anymore because of a vaccine. So we really don't want to go back to the pre-vaccine era. We need we need to be thoughtful in listening to people's concerns about why they may not want to get vaccinated, but really give them the straight scoop about how important it is to be vaccinated, to protect themselves and their children from these diseases. While vaccines do not cause autism, vaccines do cause adults.

Rebecca Saff, MD, PhD, FAAAAI 51:09

I love that. Yes, I absolutely agree that vaccines are one of our most incredible public health advances. And I really do want to see people out there being protected from the diseases that we don't see anymore and we don't want to see again. So thank you so much.

John Kelso, MD, FAAAAI 51:24

Sure.

Rebecca Saff, MD, PhD, FAAAAI 51:26

We hope you enjoyed listening to today's episode. As a reminder, this podcast is not intended to provide any individual medical advice to our listeners. We do hope that our conversations provide evidence-based information. Any questions pertaining to one's own health should always be discussed with their personal physician. The Find an Allergist Search Engine on the Academy website is a useful tool to locate a listening of board certified allergists in your area. Use of this audio program is subject to the American Academy of Allergy, Asthma & Immunology terms of use agreement, which you can find at their website. Please visit aaaai.org for show notes and any pertinent links from today's conversation. If you like the show, please take a moment to rate and subscribe to wherever you download your podcast. Thank you again for listening.