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All Podcasts Don’t Freak Out About the J&J Vaccine (with John Moore)

Don’t Freak Out About the J&J Vaccine (with John Moore)

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Description

Dr. Bob calls up Weill Cornell immunologist John Moore to figure out what you need to know about the pause on the Johnson & Johnson vaccine. They discuss why this extremely rare side effect is showing up in J&J and AstraZeneca but not Moderna or Pfizer, how people who have received the J&J vaccine should be thinking about it, and how they think this will get resolved. Plus, John’s thoughts on how the vaccines will hold up against the various variants circulating right now.

 

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Transcript

SPEAKERS

Dr. Bob Wachter & John Moore

Chuck  00:00

In hindsight, given, I’m sure you’ve seen the survey since the announcement of the pause, vaccine hesitancy is up, we’ve seen vaccine appointments go and filled, I know you’ve made the case that hey, you know, please look, the fact that we’re telling you should give you more confidence, not less. But unfortunately, it appears that it is the reverse. Do you look at how this sort of spiraled out here? And wonder if there should have been a different way you guys handle this? Well, you

Dr. Tony Fauci 

Well, you know, what we do, Chuck, and that’s what we keep saying we leave it to the science, we have the experienced FDA, and CDC people who are looking at it and monitoring it, you know, there’s one case than 2, 3, 4. And then when they got to 6, they say we really need to pause. You know, hopefully, it’ll be a quite temporary pause to do a couple of things. One examine that hopefully there are not several more out there to alert physicians stay heads up for this. We’re concerned. It’s a very serious complication. Although it is extremely rare, as you will put, you know, you have 6 cases in close to 7 million people. The other thing about it Chuck that’s important is that you want to let the physicians out there know who might see women or anybody with this condition, that the standard way you would think about treating clots is with the Anticoagulant Heparin, that would be contraindicated in this case, because heparin could actually make things worse. So there’s a twofold reason for doing it, one, to pause and take a look in more detail about it, and two, to make sure that the physicians treat people appropriately.

Dr. Bob Wachter

Welcome to IN THE BUBBLE. I’m your host, Dr. Bob Wachter. You just heard Tony Fauci on meet the press from last weekend talking about the J&J vaccine and the prospects that it will come back into service. He hinted pretty strongly that it likely will, probably in the next week or so, and almost certainly, with some restrictions, hard to know exactly what they’ll be perhaps only in men, perhaps only in people over 50 we’ll just have to see what the investigation shows. But COVID constantly throws curveballs at us. And the J&J is simply the latest one. And we’re all processing it. It has slowed down vaccination somewhat, not terribly. But the biggest risk, of course, is if people lose confidence in the J&J vaccine, or more broadly, lose confidence in vaccinations.

Dr. Bob Wachter  02:44

Actually, they should feel just the opposite way. Because here we are suspending distribution of the J&J vaccine, after 6 cases, terrible cases, of very unusual clots, but 6 cases, out of about 7 million people who have been vaccinated, which really does show how well the post vaccine surveillance system is working. And the very, very low threshold that the federal agencies have to slow things down or stop them, hit the pause button, to see what’s going on before they open things back up. The other reason to hit the pause button was to give physicians like me the opportunity to understand what’s going on so that we can recognize it better, as well as the public, so we can all recognize this better and treat it appropriately.

Dr. Bob Wachter

So, it seems like a reasonable thing to do. Although it’s frustrating, and it is yet another speed bump on our way to full vaccination. It feels like such a big issue that we thought spending an episode talking about it would be worthwhile. And we were lucky to get as our guest, John Moore, who’s a PhD professor of Microbiology and Immunology at Weill Cornell Medicine and really one of the nation’s leading experts on vaccines, you probably have seen him quoted in the media, or seen him on television or radio, he’s been quite active. And you’ll see why, he’s a very thoughtful, actually very funny and charming gentleman who take some very complicated concepts and explain to them I thought extremely well.

Dr. Bob Wachter  04:16

While I had John, I thought it was also too good an opportunity not to talk a little bit about vaccines versus variants, a little bit about his main work, which is the HIV vaccine, and why that has been so hard, whereas finding a vaccine for COVID or several vaccines for COVID was comparatively far easier. And we also ended the episode talking a little bit about vaccine passports. And as you’ll see John is quite passionate about that issue. So I enjoyed the conversation. I think you will too. And so let us ring up John Moore.

Dr. Bob Wachter

John, thank you so much for doing this. Can you start by explaining how the J&J and the AstraZeneca vaccines work and how that’s different than the mRNA, the Moderna and Pfizer vaccines work?

John Moore

Well the J&J and AstraZeneca vaccines are both based on adenovirus factors, which are common cold viruses that have been engineered to express the source calf to spike protein. And they cause transients infections of the people immunized with these vaccines, and when the virus enters target cells the adenovirus proteins are produced, and also the engineered soft cough to spike protein. And the host responds to both adenovirus proteins which are immunogenic. And also the SARS-CoV-2 S-protein which is the one we’re interested in. As the basic principle of the vaccination program, which is to induce antibodies to the spike protein, and also cellular immunity, but most emphasis has been on the antibody response. And the adenovirus factors do this perfectly well.

John Moore  06:06

The mRNA is achieved the same goal, but in a different way. They contain no adenovirus components; they’re simply the mRNA expresses only the SARS-CoV-2 spike protein. So there are no other components that are notably or known to be immunogenic. So in that sense, it’s a cleaner antibody response. And we all know the efficacy trial results, the Moderna and Pfizer mRNA’s were in the mid-90s for efficacy against COVID. The Johnson and Johnson US trial within the 70s depends on how you cut it and where the results were, etc, etc. But somewhat lower efficacy, but it’s still strongly protective against serious disease, which is the most important parameter. Protection against mild COVID is great, but it’s not as important as protecting against hospitalization, severe disease and death.

John Moore

So up until a few weeks ago, everything looked pretty rosy. And then we hit the Johnson and Johnson side effects problem that is still being actively investigated. And around the same time or a little earlier in fact, the Europeans found what seemed to be pretty similar problems with the AstraZeneca. And these same problems have not been seen with Pfizer and Moderna. So it’s pretty reasonable assumption that the adenovirus factors specific, and now we need to figure out exactly what’s going on. So the right decisions can be made, can be made for the future use of these vaccines or not as the case may be.

Dr. Bob Wachter

You mentioned that the adenovirus vector, so it’s sort of carrying the part that we really care about the spike protein, but you say it is immunogenic it creates an immune response. Is that a good thing or a bad thing?

John Moore 

Well, it’s an inevitable thing. We have antibody responses to other than the viruses, because they’re fairly common in society when we’ve all been exposed to adenoviruses over our life. So we have antibody responses. The adenovirus vectors that were chosen by J&J and AstraZeneca are a typical, so the AstraZeneca one uses a chimpanzee adenovirus vector that we’ve never been exposed to. And the Johnson&Johnson uses adenovirus 26, which is a very rare serotype that most people haven’t encountered. But once immunized with these new vectors, you will raise antibody responses to them. And that can be for the second immunization in the AstraZeneca program, that may actually be dose limiting, it may reduce the immunogenicity of the second dose.

John Moore  08:46

The Russians with their Sputnik V vaccine, which appears assuming the data are kosher to have higher efficacy combines two different vectors, two different adenovirus vectors. One is ad 5 and the other is ad 26. And that is designed and seems to be effective at reducing the dose limiting initial response to the initial ad in the virus injection impacting on the second. So it seems to be a cleaner design for a two dose. But there we are, at the moment Johnson and Johnson is being used as a one dose vaccine, although a two-dose trial is still ongoing and hasn’t reported yet in the USA.

Dr. Bob Wachter

So one of the things that’s true in clinical medicine I imagined and your work in science, too, is when you see something that’s unusual, you’re looking at not only the statistics on that thing, but also the scientific plausibility. Was this a thing I worried about in the beginning, and if it was then it’s more likely that it’s a real effect. When you heard about these clots, maybe first for AstraZeneca and then from J&J, was your instinct that wow, this is really weird. I can’t imagine how that could happen. Or your instinct was yeah, I could see how that might actually happen.

John Moore  10:04

Well, rare events happen in vaccine trials. And when you’re immunizing, you know, 10s to hundreds of millions of people, rare events are gonna pop up. And what is important is determining are they real and vaccine related? Or are they just rare events? I mean, we heard early on, you know, man in 50s has Moderna vaccine injection goes home dies of heart attack, well, men in 50s, sometimes go home and die of a heart attack. It’s nothing to do with the Moderna vaccine injection. So you have to tune out coincidence events and try to identify what’s really linked to the vaccines, then it becomes a numbers game. And there were sufficient cases in Europe to raise red flags with the investigators and trigger the AMA to investigate.

John Moore 

And when the same or what seems to be the same phenomenon happens with Johnson and Johnson in the USA, and they’re both adenovirus vectors and the same responses are not being seen with the mRNA is, then you know, it’s a reasonable assumption to point fingers at the other response to the adenovirus components, and try and understand what’s going on. So I think there probably is something real, and it needs to be understood. And a real very rare event is either going to be serious enough to curtail the use of the vaccine, or it’s going to be manageable by finding ways to still use it and minimize the risk to people.

John Moore 

And yeah, one fact that we’ve learned is that most of the people who’ve suffered these rare side effects are women of childbearing age, men seem to be much less affected statistically, which does have potentially some medical explanation. Women are more prone to autoimmune reactions than man. So my son got Johnson and Johnson and I didn’t bat an eyelid. I thought, well, one, it’s an incredibly rare event and two is male. If my daughter had got it, I might have been a bit more nervous than last week.

Dr. Bob Wachter  12:03

As you say that, you know, the idea that a rare side effect may crop up and we may not see it until 100,000, or a million or 10 million people in the vaccinated is credible. How about blood clots, from other vaccines in the past was unusual blood clots in weird places was that on your list of the things that you were particularly worried about when we’re mucking around with the human immune system?

John Moore 

I haven’t seen report of these blood clots in other adenovirus vector trials. I mean, my background is HIV vaccines and adenovirus vectors have been used for several years in humans, J&J have a large phase two B efficacy type trial for HIV vaccine going on in Southern Africa at the moment, but these are small scale trials. I mean, these are, I mean by small scale, I mean, that typical of efficacy trials that 10s of 1000s, a few 10s of 1000s of people, which so one in a million events just wouldn’t register. Same when these vectors were used in Ebola and Zika trials. They’re not large scale enough to detect a one in a million rare events. So there was nothing on my radar screen. And I’ve not heard other people saying that this was a foreseeable risk. I think it came out of the blue.

Dr. Bob Wachter 

Yeah. And what is your and the latest thinking on the mechanism? Assuming this is a real association, not a coincidence, which I agree with you, it seems more likely than not it’s real, although very, very rare. What would be the trigger to make this happen?

John Moore 

Well, we don’t have a lot of information and there hasn’t been much time. And obviously the Europeans have had longer. And a couple of European papers appeared in New England Journal at the end of last week, and they both pointed the fingers at antibody response to platelet vector four, which would be sufficient to interfere with blood clotting systems. I don’t know the mechanism. I’m not even sure it’s been out. What is that triggered by? It’s not known. Is it a response to an adenovirus component that leads to cross reactivity with PF4, it’s plausible but not known.

John Moore  14:19

The Russians who never short of issuing press releases that promote their own agenda, put one out last week saying we don’t think this is going to happen with Sputnik V because we purify our vaccine incredibly well, the implication is you guys don’t which may not be true. And they’re saying that it’s the anti PF4 is triggered by contaminant DNA in the adenovirus preparations. While that may or may not be true, and that again needs to be looked into. So it’s just too early I think to have any certainty about what’s going on, but the consensus appears to be building that it’s some kind of host antibody response to a key component of the platelet and blood clotting system.

Dr. Bob Wachter 

Do you think the decision to pause was burdened?

John Moore 

I think it was inevitable, you have to look at the counterfactual, what would have happened if the FDA and CDC had done nothing? And then the word leaked out went around that there were these deaths or serious cases, and the FDA and CDC were doing nothing about it, there would have been a bit of a media firestorm. And so the question is, what is the least damaging path forward? And how do you minimize the effect on public confidence because in the end, that’s the bigger picture. If the public becomes scared of these vaccines, then we’re in big trouble for vaccinating our way against the pandemic, it was clearly a very difficult situation.

John Moore  16:06

And it’s probably not ideal that this pause is just going on, I don’t see why the relevant committees can’t meet almost on a daily Zoom and review data as it emerges, and decide, you know, rather than waiting for 10 days or two weeks or whenever the meeting is, can we not do this more efficiently? Can the CDC and FDA not issue guidance to for example say that these vaccines are appropriate for men or older women, but not for younger women? Which would be what the data are currently pointing to? But honestly, I’m glad I didn’t have to make that kind of decision. I think it’s tricky.

Dr. Bob Wachter 

Yeah. It’s incredibly tricky. I’m not surprised and I agree with you, I think that the initial decision was good. I think waiting a week seems like an awful long time. And that seems like it’s urgent, if not emergent to sort this out. Is that your, what’s your crystal ball tells you that they will re-approve it and limit the types of people that can and can’t get it?

John Moore

Well, Tony Fauci gave a very strong hint over the weekend. If there’s anyone who’s in a loop, it’s Tony, he essentially said that the likelihood is that the vaccines will be approved subgroups. And I don’t think he specified it, but it’s pretty obvious what he means. And also guidance gets given to hospital physicians nationwide on what to look for, and what to do and not because apparently, Heparin, which would be a standard treatment in this kind of circumstance actually makes this particular condition worse. So you know, you don’t treat what you would, you would normally treat with Heparin, and that’s really not a good idea. So physicians are now being told to be on their guard, not to give Heparin to anyone who presents with clotting disorders within a couple of weeks of a J&J shot. Yeah,

Dr. Bob Wachter 

Yeah, I think the issue is that Heparin can cause something quite similar to this. It’s a, you know, the cases that I’ve seen that look like this, where the platelets are activated and cause clots in unusual places are usually caused by heparin, which is this kind of mind-blowing thing when you’re using Heparin to thin the blood. And so it’s prudent to stay away from it in favor other blood thinners and other treatments. At this point, I think you mentioned there’s no signal that the Moderna or Pfizer vaccines have any of the same problems that scientifically plausible? Is that what you would expect that because the platforms are so different, there’s no good reason to think they would cause similar problems?

John Moore  18:37

Yeah, again, it’s two versus two, we have two adenovirus vectors that seem to have a similar problem, two mRNA’s that don’t seem to have a similar problem. Probably something to do with the adenovirus vector itself or a contaminant of the Russians are right. So it’s not been reported in the mRNA’s, which have been in large numbers of people and hundreds of millions of people in Israel, in Europe and in the States. And these have just not been reported. So it’s hard to imagine they’re suddenly going to appear. They look to be very clean from this perspective.

Dr. Bob Wachter 

If you had gotten the J&J vaccine, and there are about seven or 8 million Americans that have, would you be worried right now?

John Moore

Personally, no, not at all. I’m not in a bigger risk group and I don’t kind of worry about things I can’t control, if it happens, it happens, but I’m not gonna I wouldn’t be spending my life fretting about it. No, I think it’s just an incredibly rare event. And if any individual who is in the, you know, within two weeks of J&J and we’re pretty much out of the window now should be on the lookout for the symptoms that have been reported. Stomach upsets, sore legs, anything associated with thrombosis, any signs of outbrain malfunction, you know, inability to think, concentrate, anything serious that would be, you should immediately go and see a physician. But I personally wouldn’t be agonizing over as at this point now.

Dr. Bob Wachter  20:06

Yeah. And we had a couple of vaccine experts on about a month ago, and I posed the question. Often the question gets framed, if you could get the J&J, this is pre-clots, before we knew of this problem, if you could get the J&J now, or would have to wait a few weeks or a month for Pfizer or Moderna, which would you choose? And the answer is always, you know, you get whichever one you can get quickly. But then I asked them, if all three were available and equally accessible to you, which would you prefer, and they, both of them said the J&J.

Dr. Bob Wachter 

And mainly because of the ease of use in a single shot, and one and done and they weren’t bothered by that mild difference in efficacy, because the big efficacy number that we care about, which is how protected they are around getting very sick and dying is comparable. First of all, how did you feel a month ago? And how has that changed, if at all, if you were given a choice, let’s assume next week, the J&J is re-approved, and but not for women under age 50. And you’re not in that group and you have a choice of any of the three. Does this change your thinking about which one you would take?

John Moore

I think a lot depends on your individual circumstances. To me, one dose versus two dose just wasn’t a factor. I mean, I have the privilege of working in a medical school, it would not be difficult to go for two doses. I would go for the Pfizer on the grounds it’s the most potent or equally potent, Moderna and is slightly less reactor genic. In fact, I’m in the Novavax phase three efficacy trial, and I get my crossover phase tomorrow. So I may have got the placebo a month ago, or two months ago, and tomorrow, if I got the placebo, I’ll get my first active shot, or vice versa. It’s a crossover. And so in fact, my immediate family got will get four different vaccines. My wife got Pfizer, my daughter got Moderna and my son got J&J and I’ll be in Novavax. So I think that may actually make us a literally unique family in America.

Dr. Bob Wachter  22:03

That’s really impressive. I have a couple questions. But first of all, when you say the Pfizer has less immunogenicity, so for folks that reacted, so that means less likely to cause you to feel crummy the day or two after the vaccine?

John Moore

Yeah, I think there’s enough data to say that there’s, I mean, it’s again, it’s a mild difference, it’s not something that should matter to people. But the Moderna vaccine has 100 micrograms of mRNA per dose, and Pfizer is 30. And it looks like Moderna went for a bit of overkill. And that’s probably the wrong word. But they biased on the upside and 30 micrograms is sufficient, and that is associated with slightly fewer minor adverse events, headaches, and whatever. So, if you’ve given an absolutely straight choice, which or not, and it’s a distinction without a difference in practice, I would have chosen Pfizer over anything else.

Dr. Bob Wachter 

And interesting, even though it’s more powerful, and you say that maybe causes some problems in terms of reaction, your senses, it doesn’t cause any difference in the data, doesn’t support any difference in terms of its ultimate effectiveness as a vaccine.

John Moore 

No. And in fact, Moderna did a dose change study recently, they have the dose in the phase one trial, and showed that the antibody response was the same as the original dose. So they can use 50 instead of 100 micrograms and get essentially exactly the same antibody response. And this isn’t a criticism. I mean, this time last year when they were designing the trials, normally in a, you know, non-pandemic crisis, you would do dose ranging studies, and identify by experimentation, the most appropriate dose to use, but they didn’t have the time. So the two companies made best guesses, educated best guesses, and they didn’t get it, but they both got it outright. But it turns out that Pfizer probably got it righter than Moderna. And then that’s not a criticism. It’s an inevitable consequence of the kind of situation we were living in this time last year.

Dr. Bob Wachter  24:01

Yeah, interesting. Maybe you can explain something to me that I’ve had a hard time explaining to people, knowing very little about Vaccinology and Immunology. I tell people when they have a really crummy day after the vaccine, that they should be glad that is the vaccine working. And it’s doing its thing. And then when they have no reaction, they say, well, maybe it didn’t work in me. And I say no, no, no, the reaction, the level reaction has nothing to do and you’re just as vaccinated as you would be if you’d had a reaction. Those two things seem to be in conflict. And I find myself doing a little hand waving when I describe it. Can you tell us why that’s true, If it is?

John Moore

Your reaction is perfectly logical. You would think there would be a connection but studies were done in the phase three or post phase three, to look at whether there was any correlation between sore arm, an antibody titer and it wasn’t found. There is no correlation. There’s no predictive value. So I don’t know if it’s known why, I don’t know why but there is no predictive value. And you know, different people respond in different ways to vaccines in general, when I get my annual flu shot, which I don’t always get, but I certainly have been recently, I never noticed that I don’t get a sore arm for the annual flu shot. The only reason I know I’ve been stuck is I got a piece of sticking plaster on my arm in the shower next day. But other people say, oh, I don’t like it gives me a sore arm to which you say, oh, come on, grow up. But different people respond in different ways. We’re an outbred population.

Dr. Bob Wachter

Yeah. But the key point is that the lack of that kind of response to it doesn’t mean that it didn’t work. It’s just as likely that it has worked. You mentioned that your work has been in HIV vaccines, which is a hard field. But one of the things I’ve pointed out to people who don’t really understand how miraculous it was that we went from a new virus to wildly effective vaccines in 10 or 11 months, that really smart people at a whole lot of funding has gone into trying to find an HIV vaccine for guess about 40 years. And we’re not there, describe that battle and why has that been so hard?

John Moore  26:11

Yeah, I’ve become a long-term nonprogressor. It’s a challenging field. It’s not one where you get instant gratification. It’s a long haul, grinding out incremental progress. You know, sometimes it’s an increment more often it’s an excrement. I mean, you just have to get it out and stick with it until it’s time to retire, and maybe some smarter people finish the job.

John Moore 

The Coronavirus has turned out to be a lot easier to immunize against, I mean really, it’s no comparison, the HIV variability, I mean, we may talk about variants, and they’re a fact of life now with coronaviruses. But with HIV, it’s just orders of magnitude more problematic. HIV varies essentially on a daily basis.

John Moore 

Whereas with coronaviruses, we’re talking about months, two years for the same, you know, timescale, for the same degree of variation. Plus Coronavirus have this, you know, site of vulnerability, it’s sort of a jargon term, it’s that the point at which they are most vulnerable to antibody attack, and it’s sitting out there like a sore thumb sticking out there saying hit me, whereas, and that’s the receptor binding domain on the spike protein.

John Moore

And that’s what most neutralizing antibodies are raised against. There are other domains, but most of them are against the RVD, sometimes called the notorious RVD. You know, we don’t have an equivalent in the HIV spike protein, it’s a much more shielded receptor binding domain, it’s much more difficult for antibodies to get at that, you know, it’s a different beast, and it’s just an equals HIV, Virology and Pathogenesis are more problematic than Coronavirus. Everything about HIV is difficult.

John Moore 

You know, we would not have succeeded last year in making a vaccine if the new virus have been anything like HIV. And that’s why there was a fair amount of skepticism about whether or not these programs would achieve, we didn’t know enough, this time last year to say confidently yes we’ll have a vaccine vaccines that are approved by the end of 2020, which, you know, was an amazing accomplishment. But it was also not built on nothing. I mean, all of these technologies were recycled, repurposed from existing vaccine programs. I mean, the adenovirus vectors have been used for HIV, Zika, Ebola, mRNA’s have been around for a decade less well used, but certainly not a brand-new technology.

John Moore  28:42

The VRC was in a position, BioNTech in Germany was in a position to exploit existing designs to tweak them for the coronaviruses. Protein sub-units with Adjuvants is again a proven technology. It could be exploited by Novavax and multiple other companies and now in that space, so all of these methodologies could be rapidly exploited, in a time of pandemic to come up with new designs that turn out to work extremely well. Yeah, I

Dr. Bob Wachter 

Yeah, I think the important point that even though we have not yet found the magic HIV vaccine, we have learned a lot from that effort. And some of that turned out to be useful for COVID. Do you think it’s going to go the other way? Are there things that we’re learning from the COVID vaccine work that may turn out to be useful for HIV, or we already knew everything that we know with HIV, and it just turns out to be a really hard problem.

John Moore 

Well, mRNA HIV vaccine programs are being emphasized. It’s not that they didn’t exist, but they’re now being prioritized by several well-funded groups, including the VRC to see if that will make a difference. I think it might be useful. I don’t think it’s sufficient because the immunogenicity problem of the HIV spike exists however you present it, but it’s certainly relevant technologies and some of the designs are going to be impressive. I mean, I’m not going to get into the technicalities on a COVID talk, but it could be a useful contribution.

John Moore  30:17

And you know, everything. Knowledge is always translatable. I mean, a lot of the fantastic immunology of COVID is based on methodologies that were established for other viral infections, including influenza or HIV. I mean, the investment, the country’s investment in science over the past several decades, becomes incredibly valuable when you really need it in a pandemic. So all the more reason to continue to support NIH and other federal and charity programs in the sciences, because when you need them, they better be around.

Dr. Bob Wachter

So you mentioned the variance. Let’s pivot a little bit to talking about your current thinking about the it seems like the vaccine versus variants question has been the dominant theme of the last couple of months. So where do you think we’re landing today? Are we winning that battle? Or if we’re not?

John Moore 

I think it’s too early to tell, we’re not certainly losing it, but we’ve not won it. I mean, variants, you know, they’re on the radar screens most of this year, but in fact, the first variant arose in March-April 2020. It’s called D614G. It arose most probably in ski-resort areas in Italy, you know, Italy, Switzerland, something around that part of Europe. And it is more transmissible as a variant, not by a huge amount, but by enough that it would overtake the original Wuhan strain and become the dominant strain worldwide within about 6 months, 4 months. That’s the virus that until the end of this year dominated the US pandemic, it wasn’t the original Wuhan strain, Wuhan strain was replaced by D614G.

John Moore  32:17

We got a bit complacent I think about that, because it was a bit more transmissible, but it had no impact for antibody responses. And then you can only find variants if you’re looking for them. And the Brits have done this particularly well, the Brits have done a lot of things very badly. I’m British heritage, and I can criticize my old country or like, what they did do extremely well always have very good genetic surveillance systems that track sequence evolution, and they found a highly transmissible variant called B117 that emerged in Kent County in Southeast England, dominated the UK pandemics, spread to Europe, spread to other countries, it obviously entered the USA, and it’s now probably the dominant strain in the USA.

John Moore

And it spreads more rapidly, it’s something like 60% more contagious. People with it seem to produce virus for longer, and it has a higher affinity for the ACE2 receptor. And that’s probably contributing maybe infecting kids more easily. It’s different reports suggested either is or is not more lethal, or a couple of reports said it’s 60% more lethal for people who get it. Recently, there have been a couple of other reports that says, well, maybe not so we’re not sure. But it’s not antibody resistance, are not to an important extent. So it’s not going to have an impact on vaccine efficacy, we pretty confident about that.

John Moore 

The more troubling variants for vaccine efficacy are V1351, which arose in South Africa and P1, that’s came from Brazil. And there’s a New York variant, B1526  that has the same mutations. There’s a new one in India that seems to be dominating the Indian pandemic B1617 and that’s also got troubling mutations, and they create a degree of antibody resistance. Now, what we’re unsure about is how that translates into any reductions in vaccine efficacy. I think the consensus is that it will not knock out vaccine efficacy. It’s not a wipeout, but there could be some degree of compromise that we could take 90% down to 75%. I mean, I’m not exactly plucking numbers from the air, but nor am I stating them with confidence that models projection.

John Moore  34:40

So but probably, again, protection against severe disease and death would still be in place so that would you perhaps get mild COVID but wouldn’t die with one of these variants if you’ve been fully vaccinated. But, you know, B1351 in South Africa was sufficient to take out the AstraZeneca vaccine completely. I mean, the AstraZeneca vaccine failed completely in South Africa in the face of B1351. So, these variants that call variants of concern, and they’re not called variants of mass panic, they’re called variants of concern. And that’s because we are concerned about them. But, you know, most of the virology and vaccine community is not freaking out when monitoring this and vaccine manufacturers are re-designing the vaccines to try to adjust the composition, for example, make a new mRNA, or a new protein vaccine, or a new adenovirus factor that incorporates the sequence not of the original Wuhan strain, but of B1351.

John Moore 

So that we can raise antibody responses to that variant and boost protection. And there have been a couple of trials, not really reported just known about of B1351 variants. Moderna has done it, Novavax has done it. And the antibody responses look encouraging. There was a recent paper out of Sweden in an animal model, monkey experiment, the results looked encouraging. So now, these new variant vaccines are being designed, they’re being tested, they can be produced in large amounts. And if we need them later in the year as an additional boost, they’re going to be available, because we’ve had time to plan unlike this time in 2020, we didn’t have time to plan. This time in 2021, you can see what’s evolving, and you can take steps to deal with it. And that’s again, science in action.

Dr. Bob Wachter  36:42

And is your crystal ball say that that will be what happens this fall or sometime next year, we will be getting another shot and it will be a rejiggered vaccine against the vaccine potentially vaccine resistant variants?

John Moore

I think it’s plausible. I mean, the question is how much these vaccine resistant or relatively resistant variants spread in America, at the moment, B117 appears to be squelching them out. Which you know, in one sense, it’s a good thing. It’s all a competition for space in the human population. These various variants are all competing with each other for dominance and the one with the most transmissibility will dominate might change in the vaccinated population, if everyone’s vaccinated, then a resistant virus has a selective advantage and may become dominant. So you know, the CEO of Pfizer last week said he’s anticipating a third boost with the Pfizer vaccine for Pfizer vaccine recipients, I assume the Moderna CEO would say the same thing. Whether that would be a third dose with the existing vaccine, or a third dose with a variant vaccine, I think remains to be determined. But it’s prudent to plan for both eventualities and see how the situation evolves later this year or next year.

Dr. Bob Wachter 

It’s so remarkable. I you know, finding ourselves rooting for the UK117 variant to win this race when it’s a much nastier virus than the original version. But just it seems like the dominant issue now is the vaccine resistant issue. And so even a more infectious and more virulent virus is still better than a vaccine resistant virus and in our future.

John Moore  38:23

Yeah, the most troubling variant that we’ve seen is the South African B1351, because it’s greater transmissibility. And it dominated at once it appeared in South Africa, it rapidly dominated the pandemic, it replaced the previous common virus, and it’s antibody resistant. The P1 from Brazil is sort of South Africa light, it doesn’t quite have the same degree of resistance, but it causing a lot of problems in Brazil. So none of these is good variants. But in from purely from the vaccine resistance perspective, B117 is not as scary.

Dr. Bob Wachter 

It’s not exactly your field. But I know you’ve thought about the issue of immunity verification or authentication or passports, just from where you live as an immunologist, and a vaccine expert. Do you think it’s a good idea or a bad idea? As we plot what life is going to be like over the summer?

John Moore 

I think it’s a good idea. I think it’s; it could help. So variants are obviously a big problem that we’re all wising up to and trying to come up with solutions to and it’s rooted in science, but the fact that a very significant fraction of Americans simply refuse to be vaccinated and refuse to be masked, whereas to track is a very worrying dynamic. And it’s concentrated among Republican voters in red states, if up to 40%-50% of Republicans are refusing to take vaccines. We’ll never be able to vaccinate the country out of a crisis. And you know, the irony here is that the people who most, you know, rant on about freedom, I want my freedom back other people who are least willing to do what is necessary to regain that freedom.

John Moore  40:08

I mean, that ran that Jim Jordan did against Tony Fauci in Congress last week was you know epitomize the nature of problem. He wants his life and his constituents life to go back fully to normal, but he won’t act as a leader, and give the advice to those constituents and other people who listen to him to go and get vaccinated, because that is the best way back to the freedom you want to have. And this is a, you know, Fox News, which obviously, I don’t watch, but I read about as full of people questioning vaccines and emphasizing all the negatives and not emphasizing the positives. And we are in this incredibly polarized society that vaccines are rejected by a significant number of people, not on true concerns grounds but on political grounds.

John Moore

And it’s a government intervention, therefore, it’s bad. Well, if you put in corporate imposed vaccine passports it would not, it’s not going to happen at government level, it’s a certainty that the Biden administration will not do this. But if corporate America says you want to use our services, get vaccinated, you want to get on a plane, show your vaccine passport, your vaccine confirmation certificate along with your boarding pass. And then if you’re a vaccine refuse Nick and you want to fly from California to New York, well, your option is get vaccinated or rent a car and drive yourself.

John Moore

You want to go on a cruise, or do you want to watch the boat depart from the dock, just standing there watching? You want to go to NASCAR event? Well get vaccinated, if not, you watch it on TV. I mean, you got you know, it’s choice, do the right thing and get vaccinated or not. You know, I think something like this could drive people, it might sound coercive, but it might drive more people into getting vaccinated and help end the pandemic. I mean, it’s sounds pretty desperate measure. But if we ended up with 40% of the country simply not vaccinated, we will not naturally end the pandemic, we will see more variants arise. And we’ll be having this conversation a year’s time. So radical solutions are going to have to be considered, well we don’t have a way out of the pandemic.

Dr. Bob Wachter  42:21

Yeah, yeah. Well, it is immensely complicated. And I am grateful to you for explaining it beautifully. All of these tensions, you know, many of us knew very little about anything in Immunology, Vaccinology, Virology until a year ago, and it’s hard for, even for me, as a physician of truly understanding all of it, you’ve done a terrific job explaining it and really appreciate it.

John Moore 

Thank you. I always enjoy intelligent conversations. If it can help educate the public, we’ve had to do a lot of it this year, we do it with family, with friends, we do it with contacts, we do it with media, and it makes you think, you know, explaining things to people who can pass then pass along accurate information is part of our job. So I think we’re all happy to do it.

Dr. Bob Wachter

Absolutely. Well, thanks again to John Moore for a really interesting conversation about the J&J vaccine, but much more about the different issues with vaccinations, and particularly the tension between vaccines versus variants. And again, I was really struck by John’s passion about potentially using vaccine authentification or vaccine passports. I think that comes from someone who has been spending his life working on trying to find effective vaccines and how frustrating it has been to not find a vaccine for HIV after we’ve been working on that for 40 years. So now that we have found the really miraculously found several safe and effective vaccines for COVID, that can get us out of this pickle that we’re in, the fact that a fairly large slice of the American public seems unwilling to be vaccinated is I think you could tell him his voice, immensely frustrating, and we’re all looking for solutions to that.

Dr. Bob Wachter  44:21

Obviously, the best solution would be education, and people understanding the relative risks, the safety of these vaccines, the efficacy of these vaccines and making a good choice. But if that doesn’t work, I’m with John, I think it’s reasonable to consider having vaccine passports and limiting access to certain things based on your vaccination status. But that debate will not go away anytime soon as I’ve predicted for months, that is going to be the hot issue for the summer. We have a number of other great episodes coming up here on IN THE BUBBLE. We’ll talk to Nicki Laurie, who ran pandemic preparedness under the Obama administration and now has a senior role in working on vaccination. at a global level, we’ve spent a lot of time on the show talking about the domestic situation as it comes to vaccines and variants and more not very much time in the last several months talking about the global scene and the global scene is critically important not only on ethical and human grounds, but as has been said, almost to the point of cliche.

Dr. Bob Wachter

If we’re not successful in vaccinating the globe, we here in the United States will not ultimately be safe because we’ll see more cases, imported and ultimately more variants. So really interesting discussion with Nick and Lurie. We’ll also talk to John Halamka. John is one of the nation’s experts on technological transformation and healthcare. And we’ll spend some time thinking with John about how COVID has accelerated the digital transformation of healthcare and his role leading that work at the Mayo Clinic. He really is at the leading edge of thinking about how to take advantage of artificial intelligence, telemedicine sensors, all sorts of new tools that now were available to us, we had figured out how to use it in the service of improving patient care, and also cutting costs, and John will describe what’s happened during COVID and where that might lead us as we come out of the pandemic.

Dr. Bob Wachter

Finally, we’ll have a terrific show on COVID and health equity. We’ll have three guests, one, Rhea Boyd, we’ll talk about particular issues around equity, including equity as it pertains to vaccination in black populations. We also have Diane Havlir and Jon Jacobo. Diane is a colleague of mine at UCSF. John is a community activist in San Francisco and they have partnered to do some remarkable things in both testing and vaccination in the Mission District, the Latinx district in San Francisco. It’s really an inspiring story and I think you’ll enjoy hearing that episode. I look forward to having you join us IN THE BUBBLE for these upcoming episodes. Until then, I hope you get vaccinated please stay safe and we will talk soon.

CREDITS

We’re a production of Lemonada Media. Kryssy Pease and Alex McOwen produced our show. Our mix is by Ivan Kuraev. Jessica Cordova Kramer and Stephanie Wittels Wachs executive produced the show. Our theme was composed by Dan Molad and Oliver Hill and additional music by Ivan Kuraev. You can find out more about our show on social media at @InTheBubblePod. Until next time, stay safe and stay sane. Thanks so much for listening

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