This transcript is auto generated and unedited.
>> Howard Bauchner: Hello, and welcome to Conversations with Dr. Bauchner. Once again, it is Howard Bauchner, Editor in Chief of JAMA. And I'm delighted to be joined by John Moore. John's a Professor of Virologist at the Weill Cornell Medical School in New York, and he's written a very provocative viewpoint for us entitled, "Approaches for Optimal Use of Different COVID-19 Vaccines. Issues of Viral Variants and Vaccine Efficacy." Broad topic: many issues to discuss. But let's start with the larger frame, John. How have you begun to think about the emerging variants?
>> John P. Moore, PhD: Well, there are two types of variants. I think we need to understand those different categories. The first type are more transmissible. They are more likely to infect people on average by 30-percent to 50-percent, compared to the strain we're both familiar with that's been dominating the US pandemic. Then there's a second type, which actually are more of a concern to us, or at least to me, that are antibody resistant that could affect the efficacy of some vaccines to a certain extent that we can't yet quantify. And of course the combination is possible that you could get a more transmissible and vaccine-resistant variant, but--. So the two different mechanism, they arise for different reasons with in virus evolution, and they have different implications. The ones, the most spreading, are the more transmissible variants, the B117 that arose in Kent in the UK, it's predicted to dominate the US pandemic sometime this month perhaps. I mean, there's projections; we're not sure. But it is becoming more and more widespread. Fortunately, the resistant-- the antibody resistant variants are, at present, much less frequent. But they do think that more of a concern.
>> Howard Bauchner: John, have you been surprised by the rapidity with which these variants of concern have emerged?
>> John P. Moore, PhD: Well, yes and no. We first saw this last April/May when a variant called D614G that was more transmissible. Eventually, within a space of a few months became to be the dominant strain worldwide. The original Wuhan Strain was overtaken by D614G within a few months. So we were aware of it, but kind of tuned it out until around December and January when more and more variants started to be reported. And it'd partly because they're being more looked for. If you don't look for them you don't find them. And the Brits have a very good--
>> Howard Bauchner: Right.
>> John P. Moore, PhD: Infrastructure here. And they found the Kent variant, and there are others, you know, other nations including the USA is now mimicking what the Brits have done to have a better surveillance network. So firstly, it's-- you only find them if you look for them, and the harder you look the more you find. But also, you know, you give an RNA virus to 100 million people and you give it a year, that's a recipe for variants emerging. But lucky that SARS-COV2 is not that variable a virus compared to influenza, and certainly compared to HIV, but it does vary, and you will see more over time as more and more people are infected.
>> Howard Bauchner: There are many questions already, but I want to wait on those questions to go through one or two of the major issues that you focus on in the viewpoint. Vaccine interval has become hotly discussed. I thought the issue had gone away in the US. I still think it is going to go away now that the Jansen and J & J product is upon us. So we have Moderna, Pfizer, Jansen, J & J; I don't there'll be any others in the next month or two. But can you go through how you have thought about this spacing that, where you were born, the UK, has begun to do? And you have a very interesting explanation as to why in certain groups of people you think that is not a good idea?
>> John P. Moore, PhD: Yeah. I think what is being done in the UK, it's educated guesswork. They're trying to wrap it up in science, but a lot of it is-- a lot of the evidence is quite weak. I understand the rationale, and it's superficially seductive. And you can see the argument, but I think they're doing a dangerous experiment that could finish up rebounding on them. The principal arguments against extending the dosing interval is that you're really not very protected in the interval between the first and second doses. Yes, there is protection, but there's data out of Israel now that shows the second dose doubles the protection. I mean it's got some sort of different parameters, but it's a very substantial increase. And the second dose strongly increases your neutralizing antibody levels. You know, 20, 50-fold, that kind of ballpark. So it's very significant. Now, if you're dealing with variants, you want the strongest possible antibody response. So a variant may-- well, there are certainly variants that we know just cannot deal with one-- one dose MRNA vaccine sera just cannot deal with the variant that arose in South Africa. It just blows right past them and then it's just like it's not there. Two-dose sera can cope because it's that much stronger to start with. So a reduction can be tolerated. So if we're dealing with variants that are spreading and are more resistant, let's have the strongest possible antibody response, and that means two doses in the FDA recommended timeline. And there's a more subtle point, but it has long-reaching implications. How do variants arise? How does an antibody-resistant variant arise? Well it arises in a circumstance where you have a meaningful, but not terribly strong antibody response. So if you have a very strong antibody response, the virus can't replicate. If you have a really weak or nonexistent antibody response, the virus doesn't care. But if you have something in between, the virus sees the selection pressure and mutates to escape it. And that's how virus-resistant, vaccine-resistant, antibody-resistant variants arise. So the circumstance where you have an intermediate antibody response is exactly the circumstance what you have after the first dose of an MRNA vaccine. You have a measurable antibody dose, but it's not that strong. And, you know, there are lots of grounds to think that this could happen; that that will drive antibody-resistant viruses. It can't be proven, but it's a legitimate concern that's widely shared when, you know, antibody people or immunologists in general. We've already seen in Britain; the Kent variant requires mutations that make it highly resistant. It's becoming like the Brazil variant, B1351. So is that a harbinger of things to come? I guess we're going to find out, but it's a troubling scenario. And, you know, the Biden Administration is very science-driven, and the science says stick with the FDA approved protocols. All the leading figures agree on this, and I just think it's the right thing to do. And it won't become an issue as more and more vaccines become available.
>> Howard Bauchner: Right.
>> John P. Moore, PhD: I mean this is-- if this is a now issue, it won't be an issue in a month or twos time when the projected increase in vaccine rollout reaches fruition.
>> Howard Bauchner: Yeah. We're also at a very fortunate time because the number of cases, hospitalized cases, and the number of deaths continue to come down. So it seems to me to be a very odd time to begin to experiment, when in general the data are going in the right direction, and we know that the Jansen, J & J product is a few weeks away from really increasing the number of doses that would be available. Plus, even with Moderna and Pfizer, I think for the first time we topped 50 million individuals have gotten the first dose, and about 25 million who've gotten the first and second dose, so 75 million. 100 million is the high-risk group, essential workers; people older than 65. So we're getting close to vaccinating the really critical group.
>> John P. Moore, PhD: Yes, that's absolutely correct and then we will get into a situation where the problem is the people who refuse to take the vaccine--
>> Howard Bauchner: Right.
>> John P. Moore, PhD: We'll have more vaccines than arms to put them in. Because there's still a significant, substantial fracture of Americans in surveys who say they simply won't take the vaccine, for any of many reasons. And if we're ever going to achieve vaccine-induced herd immunity, that will become a major, major issue. Because there's a significant fraction of unvaccinated people.
>> Howard Bauchner: Now John, you also have some very interesting comments about how, if the-- logistics aside, and I don't mean to minimize how important that is, but logistics aside, we have 2 million doses of Moderna/Pfizer available daily, and 500,000 of J & J. Let's say that's where we are in two or three weeks. That's actually a very plausible scenario. You also touch on a possible way in which that could be distributed. Could you talk about that and then comment on why you think that could be seen as a reasonable approach if you could put logistics aside.
>> John P. Moore, PhD: Well at the moment, and I don't have an issue with this, the-- this-- the three vaccines are considered to be equivalent and there's no discrimination between who should take one versus the other. You know, there's an argument to be made that you should-- and use the J & J for younger people, who if they are infected, have lower viral loads, and therefore may be better suppressed by a vaccine that is somewhat less potent than Pfizer and Moderna. And I think there's no doubt that Pfizer and Moderna are the stronger vaccines, which is not to say that the J & J vaccine doesn't make a contribution. But in terms of prevention of weak infection-- which is not really important, but you know, it's non-critical infections-- Pfizer and Moderna are stronger than J & J. So let me get to the question of do people care about that? Well they shouldn't care about that, but people do. And they-- you know, I had a message from a young science journalist the other day and saying that in her circle of friends-- not necessarily her, but her circle of age group friends, they're concerned about prevention of infection, or prevention of infection that would enable them to transmit virus to other people. And, you know, that's around; that's a concern and it needs to be thought about and managed. You know, if you're in your 20s and 30s, and you're probably not going to get terribly sick from COVID, you're interested in not getting infected at all and not having a risk of passing any infection onto your friends and older people. So these are complicated issues and there's no simple solution to it. But the key message is, the vaccines work; all three of them work. And they certainly reduce, or roughly equivalently reduce severe infections of death, and for older people that's the key message.
>> Howard Bauchner: Can you imagine-- and you talk about this in "The Viewpoint" and it gets increasingly complicated, and it is one of the questions. A mixing and matching of vaccines, and I fully appreciate that is all dependent upon what happens with the variants. But how have you begun to think about that John? Because I think the key to think about it now is so that if in July or August there's a truly resistant variant, we should be prepared for it. So how have you thought about that/
>> John P. Moore, PhD: Well, there are two ways of addressing this. I mean firstly, for a truly resistant variant, all the companies are working on redesigning their vaccines, particularly to deal with the B1351 strain that arose in South Africa, that's the most characterized of the resistant variants. And so they're just tweaking their designs. But of course it then takes multiple months to reproduce new stocks.
>> Howard Bauchner: Right.
>> John P. Moore, PhD: Another strategy is simply to give a third dose of the MRNA vaccines and the second dose of J & J, which is being tested in Phase 3 trials. I personally think that this-- the two-dose J & J will overcome any limitations to the one-dose, based on animal studies. So a second or third dose will help, in and of itself. A new variant design will also be helpful in all probability; needs to be evaluated. But vaccine combinations-- my background is HIV vaccines. And it's common in clinical trials for different vaccine designs to be used sequentially; sometimes simultaneously, but mostly sequentially. So Johnson & Johnson, for example, has a large-scale, Phase 2B/Phase 3 trial in Southern Africa, of an adenovirus vector that's very similar to their COVID vaccine, followed by a protein boost. Well, there are protein vaccines coming down the pike, being the NOVA VAX 1 is in US Phase 3 trials; I'm actually a participant in that trial. Sanofi GSK has a protein-based vaccine; run into some problems but is now back on track. So if these protein vaccines are approved, they might make excellent boosts for adenovirus factors, and conceivably for the MRNAs. And these are things that could be tested in clinical trials, I mean relatively straight-forwardly, but it would require the companies to work with each other, which we haven't seen much of yet. Although actually, the Russians and the Astro Zeneca people are doing it, starting or planning a combination adenovirus vector trial in the UK.
>> Howard Bauchner: At the moment, you would not recommend mixing and matching vaccines. There needs to be a science or an evidence-base to doing it.
>> John P. Moore, PhD: Yeah.
>> Howard Bauchner: Is that an accurate statement, John?
>> John P. Moore, PhD: That's-- and absolutely, we need trial data. I mean the FDA has said that in extreme circumstances you can get a Moderna first and a Pfizer second, and-- or vice-versa, and that's sensible. But those two vaccines are so very similar, that's distinction without a difference. I'd have no problems with that. But again, the FDA says, "In extraordinary circumstances." There's no-- been no discussion of adenovirus prime MRNA boost, but I bet it would work quite well. And I'd like to see trials in this general area including the protein vaccines for the reasons I said earlier.
>> Howard Bauchner: Have there been enough-- has enough time passed John to get a sense-- I mean some people in the initial Moderna/Pfizer trial are six-- we're six months out. So I know, obviously, they're accumulating neutralizing antibody information about them. Are we far enough out to begin to understand what booster may be necessary regardless of the variants? But just that simply, that--
>> John P. Moore, PhD: Yeah.
>> Howard Bauchner: Neutralizing antibodies tithers are dropping, or are those people going to be okay for a year or 18 months; two years?
>> John P. Moore, PhD: Well, firstly the FDA recommendation to convalescent patients is after a period of time, you know weeks, you're eligible to be vaccinated and many people are being. But there's been a flurry of preprints in-- and one published paper in Lansing, I think, from the UK showing that a single dose of the MRNA vaccines to a convalescent patient very rapidly triggers an extremely strong antibody response: it's a recall response.
>> Howard Bauchner: Right.
>> John P. Moore, PhD: And the [inaudible] that are reached within a few days to a week of that single dose exceed what people had during infection or exceed what the two doses given in naïve people. So this is an argument that a single dose in a convalescent dose in a convalescent patient may be sufficient and the French have already, a week or two ago, said, "We're only going to give one dose to convalescent patients. Well, you know, you'd be-- everyone would be happier with clinical trial data on this rather than anecdotes, but the anecdotes are quite compelling. And if you think that there are, you know, what? 30 million convalescent patients in the USA now?
>> Howard Bauchner: Yeah.
>> John P. Moore, PhD: We have a lot of dose saving. So, I think-- and the FDA has started to seriously look at this now. So it's something to explore.
>> Howard Bauchner: Is there a sense yet of-- for people who come-- as you call them, people who've been infected and then get Moderna or Pfizer, or people who weren't infected and got the two-dose Moderna and Pfizer, we're six months out from those-- and that initial group. Do we know much about what their titers look like six months out?
>> John P. Moore, PhD: Titeristic [phonetic], after you're infected you get a very rapid peak response that then decays gradually over the next six months. I mean, we're only at six to eight month timepoints from the--
>> Howard Bauchner: Right. Right.
>> John P. Moore, PhD: So-- but it doesn't disappear, and reinfection cases, except when they're triggered by a resistant barrier-- which are becoming more common-- but with the reinfection by the same virus is still pretty rare; it happens. But you also have to remember that the magnitude of the infection-induced antibody response, it's not the same for so many different severities of infection. It's strongest for the sickest patients. So people with asymptomatic or very mild infection don't have a very strong antibody response. They-- you know, in terms of circulating antibodies; they may have memory, and they may have T-cell responses as well. So again, different convalescent patients might fall into different subgroups. And that's why you'd look at a clinical trial of people who had originally a mild infection and people who had originally a sicker infection and see what a single does. Because at the moment these-- these preprints I'm referring to are all done in hospital employee study.
>> Howard Bauchner: Right.
>> John P. Moore, PhD: So you go and bleed your colleagues after they've had their vaccine. It's not a properly coordinated study, but it-- they're valuable information. I'm not dismissing it; I think it's quite compelling what I've seen so far.
>> Howard Bauchner: One of the questions is a roll of so-called Sputnik B vaccine?
>> John P. Moore, PhD: Sure.
>> Howard Bauchner: Can you imagine what role that would be in the US? Or is that largely going to be outside the US? I have no idea if the company's even planning on FDA application?
>> John P. Moore, PhD: I would be very surprised if it was-- Sputnik V was going to be used in the states, or the Chinese vaccines. I mean, we don't need them, and they would need to go through a trial program. Having said that, you know, I was very skeptical about the initial reports out of Russia, and I thought, "What the hell is Putin doing?" You know, he'd say, "We have a vaccine." And all he's done is tested it in his daughter and a few other people. But turns out that that's a pretty good vaccine and, [laughs] again, who saw this coming? It is a better vaccine than the one-- the AstraZeneca Oxford vaccine that was also based on adenoviruses. So all of these-- both Sputnik V and J & J and the Oxford AstraZeneca are all based on adenoviruses, but they're not identical.
>> Howard Bauchner: Right.
>> John P. Moore, PhD: The Russians came up with the best design it would seem. I mean again, assuming that all their published data is completely kosher, and you have to take it at face value. But their efficacy was up at 90-percent, and it's hard to argue; they came up with a good design. They're having some trouble making it, apparently, but they're trying to get it into Eastern Europe and other client states.
>> Howard Bauchner: There's a complicated question, and so if you could walk through it, John, slow. So if you could go through each vaccine against each variant, and what you know about it. Sorry, so Moderna and Pfizer against B117. So if you could walk through that and what the most recent data are about efficacy?
>> John P. Moore, PhD: Well, there's not a lot of information out there because we don't have a coordinated way of track--
>> Howard Bauchner: Okay.
>> John P. Moore, PhD: How vaccines sera. There is no-- not yet a central system for looking at all the vaccine sera against all the variants. So it's all being done on the ad-hoc basis; a small scale study as in individual universities and medical schools. I have not seen any study on J & J vaccine sera. I mean, it's not available within hospital medical schools--
>> Howard Bauchner: Okay.
>> John P. Moore, PhD: And apparently it's being, you know, the company is doing its own studies and clinical trials, and other people can't get access. So we await that result. Moderna and Pfizer sera are much more available because, like I said, in hospitals you can get access through, you know, via approved protocols and they're pretty similar, Moderna and Pfizer. The B117 variant, that is-- that rose in the UK that is wide-- more widely circulated, that is very little different from the wild-type virus in terms of neutralization sensitivity. It's two-fold, insignificant, not a concern, no one's losing sleep over this.
>> Howard Bauchner: Okay.
>> John P. Moore, PhD: So that is not an escape mutant. It's not an antibody-resistant virus, and I can't imagine it would be a significant reduction in vaccine efficacy for Pfizer and Moderna.
>> Howard Bauchner: Okay.
>> John P. Moore, PhD: It's also been tested against the Novavax sera and the Novavax sera is not a problem. There's only been one study on that that I've seen. The B1351 variant that arose in South Africa is more of a problem, and Pfizer and Moderna sera in most studies are down five-fold, six-fold each, seven-fold in titer. But that's not a catastrophe. That's a sort of eyebrow raising ground for concern, but not a freak out situation. Because the strong antibody responses to the two doses of Pfizer and Moderna should be able to cope with this. So if you reduce from a strong position, you still have a reasonably strong position. So there's grounds for concern and we need data, but it's manageable. There is one study out there that says the reduction could be as high as 90-fold, but I think that's an outlier. So-- but again, it's better to have a centralized system where all of these vaccine sera are available in-- against all the variants. The Oxford AstraZeneca vaccine essentially failed in South Africa in the face of the South African variant.
>> Howard Bauchner: Right.
>> John P. Moore, PhD: In the face of the South African variant. And again, the sera from that Oxford AstraZeneca vaccine doesn't touch the South African variant. So that's a-- you know, that's a weaker vaccine. It's being relied on heavily in the UK and some other countries, but it's a weaker vaccine and did not cope as well. And there's nothing on the others at this stage. The other variants you may have heard about, there's essentially no information on. But looking at the California variant mutations, it's likely to be a vaccine-resistant problem.
>> Howard Bauchner: Brazil.
>> John P. Moore, PhD: Brazil-- the variant in Brazil, P1, or-- is quite similar to South Africa.
>> Howard Bauchner: It is? Okay.
>> John P. Moore, PhD: Judged by its sequences, you know, judged by the sequence changes, there have been fewer studies in the literature on P1. I've seen one that says there is a reduction in sensitivity in lab tests and neutralization tests, but not to the same extent as in South Africa. So it's sort of-- based on this one study or maybe two studies, it's in between the UK B117 and the South African B1351. So it may be in between. But it's resistant enough to, you know, to be a resistant variant. I mean-- and it's also a more transmissible variant. So it's one we have to respect.
>> Howard Bauchner: John, one of the questions that comes up every time and has come up once again and involves literally millions of people in the United States, and the CDC hasn't been precise about this. You are an investigator who's focused much of your career on HIV. Immunocompromised individuals and vaccination, now we've talked about it yesterday in a small group. What do we mean by immunocompromise? It's not a good measure of being immunocompromised. Not many people know what their B-cells are, or their white blood cell counts are, so it's often based upon what your disease-- how you're labeled with the disease or what drugs you're on. Do you have a sense of how individuals who think of themselves as being immunocompromised should think about the vaccines?
>> John P. Moore, PhD: Well we definitely needs studies because of different people--
>> Howard Bauchner: Right.
>> John P. Moore, PhD: Because of different-- well, as you just said, different immunocompromising means different things to different-- and different medical circumstances. I know colleagues here are trying to get off the ground a vaccine study in cancer patients--
>> Howard Bauchner: Right.
>> John P. Moore, PhD: With B-cell suppression in some cases, and others would be less severe immunosuppression. So it would greatly vary. I mean someone who cannot develop a B-cell response isn't going to do much of a response to a vaccine. And there are studies, you know, in the literature-- natural history studies looking at people with immunosuppressive conditions and the magnitude of what the antibody response was to infection of course, and a significant number of people with immunocompromised conditions were infected during the pandemic. So there is information on their response to vaccination-- to infection, if not vaccination, and you can get some feels from this. But it really tracks with their condition. I mean, people with severe B-cell defects are not going to respond well to infection and vaccination. And, you know, there's a concern that people who are highly viremic because they can't clear the virus because of immunosuppression, there's at least three case reports of troubling variants arising within those people because they have a long-sustained viremia course that can't be cleared because there's no good immune response. So these are potentially, unfortunately, sources of resistant variance and in the hospital setting they need to be, you know, carefully looked after-- particularly carefully looked after from the transmission perspective. But we absolutely need more studies on this. I don't-- I have not seen a single vaccine study yet, and that's not surprising, on immunosuppressed patients, and I know they're being planned, and they-- it is necessary that we do things.
>> Howard Bauchner: You end up in a-- if you're a patient it's a very complicated discussion, because often times your care provider may not know that much about it. Should these individuals avoid being vaccinated, John? Or is it really a case-by-case decision? Is there a risk to being vaccinated? Or is it simply that they're not likely to respond?
>> John P. Moore, PhD: I doubt there would be a-- I'm not a physician, so I don't want to get out--
>> Howard Bauchner: No, I know, right.
>> John P. Moore, PhD: But I doubt there would be a risk to being vaccinated. It might not do them any good, but you know, I remember a story with colleagues who had a very immunosuppressed patient who was highly viremic for 33 days and then she got a strong convalescent plasma infusion which made up for her own inability to raise antibodies. Two days later she was discharged. So these are circumstances in which passive antibody therapy. Now are the convalescent plasmas or the licensed-approved Regeneron and Lilly drugs--
>> Howard Bauchner: Monoclonals.
>> John P. Moore, PhD: Passive immunity to people who cannot generate active immunity? So these are settings where you-- if you can't make your own antibodies you get somebody else's. And passive therapy is particularly valuable in that setting. Both to treat them and for prevention purposes. I mean, we know in a nursing home study that the Lilly and the Regeneron maps will prevent infection of transmission when it was done in a prevention study as opposed to treatment. And I absolutely believe that would be the case; you would see that in many infectious diseases. So these antibodies can be preventative in circumstances where people are particularly vulnerable, such as immunocompromised patients. Okay, you might have to come in for an infusion every three or four weeks, but that's, you know, definitely okay given the alternative.
>> Howard Bauchner: Two final questions, kind of the two ends of the age spectrum, I am a pediatrician by training. How have you understood the general lack of serious disease in children? We've published on MISC a number of times, but it's rare. You know, the epidemiology in terms of age and deaths hasn't changed since last February.
>> John P. Moore, PhD: Sure.
>> Howard Bauchner: Eight-percent of the deaths are in people older than 65; it's virtually unchanged. How do you understand the general lack of serious disease in particularly prepubertal children, but in children and young adults even?
>> John P. Moore, PhD: Well this is nowhere near my area of expertise. I read; I don't work in this area. I can only say what I've read. I mean there are a number of different hypotheses on this. One is that the younger people generate particularly strong responses with immune responses and rapidly clear the infection. And that seems to be, you know, a favored explanation. I've no reason to dispute that. The question is, do they have high viral loads at all? And I've seen a-- or heard of a recent report that infected younger people can actually have quite a lot of virus, which means they can spread it. But for whatever reason, it's not causing them any disease. Now that, if it's true, is important for transmission risks.
>> Howard Bauchner: Right.
>> John P. Moore, PhD: But I don't know if it explains why they don't sicken. I think we should just be grateful that they don't. But, you know, old-- we all know, there's just so much information that older and sicker patients are the most vulnerable to severe disease and death. But there's-- you know, we need vaccine trials in the kids, and this will happen. I mean, you can't do vaccine trials in kids until you have safety profiles in adults. That's the way it's always been done, but now there are trials being planned in younger people and in pregnant women. For the same kind of reason, to get additional information on who would best benefit.
>> Howard Bauchner: Last question, using your crystal ball, where will we be in August, before school and the summer vacation ends and we move into a-- yet another high-risk season. Where do you think we'll be in August, John?
>> John P. Moore, PhD: Well the optimistic perspective is that we're going to have a mass economic depression because everyone's going to be on holiday on the beach and will be spending all their frequent flier miles and just generally not being at work. And I think the economic [laughs] consequences could be quite severe. That's the optimistic perspective. The more pessimistic one, which I personally don't believe but let's go there, is resistant variants become a problem; vaccine resistant variants so that we have to rejig vaccine designs. And people then get, you know, more and more vaccinated people get infected by resistant variants, natural immunity wanes. We could see a problem. And you know, the other biggest obstacle to it is something I mentioned earlier, having a very large percentage of under-vaccinated people who simply won't take the vaccines for whatever reasons. I mean there are surveys showing that 50-percent of Republican voters will not take the vaccine. Well that's just crazy; it's not a political issue. It's a public health issue. But until we reach out into that population and persuade them to take the vaccines, we're going to have a long, large reservoir of people who would continue to be infected and spread the virus. So variants and under-vaccination are the two biggest obstacles I can see, because we know that by the summer we're going to have enough vaccine to immunize everyone who wants it. And the vaccines do work for those who take it for the viruses we have at present. So I think it's reasonable grounds for optimism that by, you know, middle to end of the summer, life could start to return to normal. But only if we maintain our discipline. And it's not over yet. I mean opening up states willy-nilly and throwing away your masks is just not the right thing to do. It's-- again, it's a political decision and not a science and public health-driven one.
>> Howard Bauchner: This is Howard Bauchner, Editor in Chief of JAMA. I've been talking with John Moore, John's a Professor of Virologist at Weill Cornell Medical Center in New York. And he's written a very scientifically provocative viewpoint entitled, "Approaches for Optimal Use of Different COVID-19 Vaccines. Issues of Viral Variants and Vaccine Efficacy." John, thanks for joining me today. There's always so many questions when we talk about vaccines, and so it was really interesting to get your perspective. Thanks again for joining me.
>> John P. Moore, PhD: It was a pleasure; I enjoyed our chat.