TTHealthWatch is a weekly podcast from Texas Tech. In it, Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine, and Rick Lange, MD, president of the Texas Tech University Health Sciences Center in El Paso, look at the top medical stories of the week. A transcript of the podcast is below the summary.
This week's topics include two RNA SARS-CoV2 vaccines, an inactivated vaccine, a look at who's willing to be vaccinated, and guidelines for managing Down syndrome manifestations.
Program notes:
1:06 RNA vaccines
2:00 Similar immune responses young or old
3:00 Inactivated virus
3:10 Vaccine hesitancy
4:10 Vaccine attributes multiple
5:12 Suggests ways to address hesitancy
6:13 Rigorously tested even for an EUA
6:41 An inactivated viral vaccine
7:42 Inactivated vaccines must be made properly
8:44 Not a narrow vaccine
9:12 Guidelines for managing Down syndrome manifestations
10:13 Literature survey
11:12 Congenital heart disease common
12:45 End
Transcript:
Elizabeth Tracey: When a SARS-CoV-2 vaccine comes across the transom, will you take it?
Rick Lange: Report on a promising inactivated whole-virion COVID vaccine.
Elizabeth: What's the best care for people with Down syndrome?
Rick: And the safety and immunogenicity of two RNA-based COVID vaccines.
Elizabeth: That's what we're talking about this week on TT HealthWatch, your weekly look at the medical headlines from Texas Tech University Health Sciences Center in El Paso. I'm Elizabeth Tracey, a Baltimore-based medical journalist.
Rick: And I'm Rick Lange, president of Texas Tech University Health Sciences Center in El Paso, where I'm also dean of the Paul L. Foster School of Medicine.
Elizabeth: And right now in the nation's hotspot, I would say, relative to battling COVID-19. How's it going?
Rick: You know, it's really tough here. I think we have the highest number of cases per capita across the U.S. and increasing. It's a really tough time in El Paso right now, so some of the stuff we're talking about is very relevant.
Elizabeth: Yeah. Let's turn, then, to... why don't you talk about the first vaccine candidate that you'd like to illustrate?
Rick: Okay. This is a report from Pfizer and a company called BioNTech that is one of those vaccines that's in phase III trials, so this is the initial report of their phase I and phase II trials. BioNTech and Pfizer launched a coordinated program to compare four RNA-based COVID-19 vaccine candidates. They did it in Germany initially and then brought it to the U.S.
This is a report on two of those RNA-based vaccines and how they decided for one over the other. I'm going to call them B1 and B2, because that's what they call them. B1 is a RNA vaccine directed towards the receptor-binding domain. They took three of these domains and actually bound them together, which could be more antigenic, and the B2 was they took the whole spike protein.
They tested these in individuals 18 to 55 and those 65 to 85, and they did multiple different doses of these. What they discovered is that in both the younger and older individuals, they elicited similar immune reactions. The one directed towards the spike protein caused less side effects and that's the one they're testing in the U.S. in phase III trials.
One of the things they're going to be dealing with is there are four phase III trials here in the U.S., other phase III trials around the world, at least 39 different places the vaccines are directed. There are over 200 candidates. As we test these things globally, we're going to have to decide which one's the safest and most effective.
Elizabeth: That's the thing, I think, that I'm finding really interesting is all of these modifications and lots of speculation that's elsewhere in the literature about which of these is going to turn out to be both the most efficacious as well as having the least side effects, with some concerns that have arisen with two other front-runners right now, which are in this adenovirus vector, that may end up actually potentiating responses against SARS-CoV-2.
Rick: We'll talk about that with the next type because these are not thought to, but in the inactivated virus it could be inactivated in a way that can actually potentially increase infections. We'll talk about that when we talk about the next trial.
Elizabeth: That was in the New England Journal of Medicine. Let's turn to JAMA Network Open. When we talk about vaccines, of course, the question is, "Is anyone going to take the vaccine once it is available?" Of course, here in the U.S., it's surrounded by so much controversy that's largely political in nature, although what is termed "vaccine hesitancy" is certainly something that predated our current political turmoil.
This study took a look at a population -- and it was supposed to be a representative population -- of people around the U.S. and asked them -- created these scenarios where they said, "Hey, talk to me about whether this would be a vaccine that you would be interested in taking or not."
They recruited 2,000 people. They ended up with 1,971 -- 51% were women, 73% were white, 14% Black, and 10% Latinx -- participants being asked to evaluate two hypothetical COVID-19 vaccines and whether they would choose A, B, or neither.
Vaccine attributes included their efficacy, protection duration, major adverse effects, minor adverse effects, Food and Drug Administration -- whether it was an emergency use authorization or a full authorization -- where did this vaccine come from, and who was endorsing it.
Basically, what they found was that people said -- the majority, actually, of their respondents -- said, "Hmm. If this was an emergency use authorization, I'm not going to take this vaccine." More people also said, "I won't take it if it originated from China." And of course, Russia's working with some things too, so I would kind of throw their vaccine into that mix and say if it was coming from there, probably more people would not take it also.
Then with regard to who's endorsing it, if it was endorsed by President Trump, fewer people would take it than if it was endorsed by Anthony Fauci et al. It's an interesting snapshot of reluctance to take vaccines and suggests, of course, ways that we can kind of hopefully package things ahead of time so that it's more acceptable to people to take it.
Rick: This goes to the issue of building trust to achieve confidence in the COVID-19 vaccine, so this information is really important. We have people around the world, and certainly in the United States, that are just hesitant to take any vaccine. That has been based on inaccurate science and misinformation, so we need to be transparent if we talk about how it was approved, where it came from, who endorses it, and what the safety and efficacy is. We need to do that often to do it to build trust.
Elizabeth: Exactly. I think that making this distinction between full approval and EUAs is also really important, and it's not appreciated by the public at large. I don't blame anybody for not understanding it. It absolutely seems Byzantine to me, even, sometimes, let alone if it wasn't part of my world.
So I think that it's really important for us to convey that that doesn't mean that we're just sort of knee-jerking it and letting it out there. I mean, it has been through an awful lot of rigor previous to that.
Rick: It has been. It's been tested in tens of thousands. We have at least 2-month follow-ups, but you're right. The only other time we've used an emergency use authorization (EUA) was in 2005 with the anthrax vaccine because of the concerns about anthrax, so you're right. It's not the usual mechanism and so there will be some concern about it.
That's why we need to be transparent and let people know, "Here's what we've done and here's what the FDA has done to assure to their best ability it's safe and efficacious." It's going to require some good communication.
Elizabeth: Continuing, then, with our exhaustive vaccine survey, it seems like for this week, let's turn to the Lancet Infectious Diseases for another vaccine that's out there being tested.
Rick: We just talked about the RNA vaccine. This is an inactivated SARS-CoV-2 vaccine. This is a double-blind, placebo-controlled phase I and phase II trial conducted in China, again, looking at two age groups, those under the age of 60 and those over the age of 60, using, again, an inactivated virus.
It required two doses. The older group had lower rates of adverse side effects than the younger group -- that was 47% versus 19% -- with most of those being fever and pain. The vaccine was similarly immunogenic in both age groups, which is good.
It tested positive against several drifted isolates, so that suggests that as there is genetic variations this particular vaccine could be effective. It's usually given at 0 and 28 days. They did it at 0 and 28, 0 and 21, and 0 and 14 days, but the 0 and 14 days didn't give the same immunogenic response.
As we talked about, these inactivated vaccines have to be made properly. Improper inactivation can actually alter the antigenic properties and it results in the induction of non-neutralizing antibodies that actually enhance the disease rather than protect against it.
While this study came out, another study in a different journal suggested the same thing, that an inactivated whole virion vaccine could be immunogenic and safe in phase I and phase II trials.
Elizabeth: I would just say I'm hopeful that at the end of all of this we're a) going to have a much more nimble vaccine production process that is really based on a lot of the characteristics of the particular virus that we're trying to vaccinate against and that b) we're going to find out what the best strategies are for all the different types of viruses that are out there, both DNA and RNA viruses, and single-stranded and double-stranded, and enveloped and non-enveloped, and all the rest of that stuff. I still have some concerns about natural infection subsequent to immunization.
Rick: Yep. Again, you don't want it have such a narrow vaccination that as there's genetic variation in the virus, that you're still not having an immune response. But I am heartened by the fact that when you think about it, the first infection occurred pretty much in January, and 9 months later, we have a number of different vaccines that are on the drawing board and in phase III trial. The speed with which that's happened is just essentially unheard of before.
Elizabeth: Good news. We like those hopeful notes, so let's turn to another hopeful note in JAMA, a look at something that, to me at least, is astonishing, that it appears that nobody really has ever taken a comprehensive look at this particular issue before, and that's guidelines for care of adults with Down syndrome.
Down syndrome, trisomy 21, is the most common chromosomal abnormality among people born, actually, worldwide, with 1 in 700 infants in the U.S. being born with Down syndrome, so that's quite a lot.
It used to be, lo these many years ago, that these people suffered truncated lifespans and a lot of other kinds of morbidities during their lifespan, and now they're having a median lifespan 57 years, with reported survival up to the age of 82, which, to me, sounds truly amazing. Clearly, people are doing a lot of good work, even though they're not getting together and talking about this.
So this workgroup developed it's called the Global Down Syndrome Foundation Medical Care Guidelines for Adults with Down Syndrome Workgroup. Wow, really a mouthful! What they did was survey the literature out there to find out, "Well, all right, what comprises best care?"
Out of an astonishing almost 12,000 literature citations, they were only able to identify 20 relevant studies. Out of that number, after they reviewed it, they came up with only one strong recommendation for the care of these folks, and that was for screening for Alzheimer-type dementia starting at age 40 years.
They do have a lot of other recommendations that are less strong and those are relative to things like risk factors for cardiovascular disease and stroke prevention, screening for obesity, looking at secondary causes of osteoporosis, recommendations for diabetes screening, and shorter intervals, because folks with Down syndrome happen to have that more often and it's earlier onset.
Rick: When I was in my training, their average lifespan was 25 years, and that's usually been accomplished because about half of them have congenital heart disease and now we can address that, many of them have respiratory illnesses, and many were institutionalized before.
Again, this is the first time in either of our lifetimes these guidelines for care of adults with Down syndrome have been assimilated and published. What do we do with that information? It makes us aware of what conditions we need to screen for and recommends screening activity, so I applaud the authors, MDs, PhDs, and social workers who took on this daunting task of providing these recommendations.
Elizabeth: Indeed. They also taught me something new -- which I had not been familiar with this term before -- atlantoaxial instability, that in fact there's a cervical spine, I guess, weakness, if you will, in people with Down syndrome and that they can actually suffer from that condition. I thank them for teaching me a new term.
Rick: Right. In the past, because the cervical spine abnormalities were there, there was some thought, "Well, maybe we need to do routine X-rays on these individuals to prevent them from having spinal cord injuries." What the studies suggest, as they have mentioned it, that doesn't need to be done.
In fact, we have over 50,000 kids participating in Special Olympics and they've never had an issue with spinal cord injury as a result of that. Again, very thoughtful, knowledgeable, and evidence-based recommendations.
Elizabeth: We like that. On that note, that's a look at this week's medical headlines from Texas Tech. I'm Elizabeth Tracey.
Rick: And I'm Rick Lange. Y'all listen up and make healthy choices.