You’re listening to a press conference from the Harvard School of Public Health with Barry Bloom, professor of immunology and infectious diseases and former dean of the school, and William Hanage, associate professor of epidemiology and a faculty member in the Center for Communicable Disease Dynamics. This call was recorded at 11 a.m. Eastern Time on Tuesday, December 22nd.
MODERATOR: Dr. Hanage, would you like to go ahead?
BILL HANAGE: Hello, everyone, I want to start by wishing people compliments of the season and to explain that just something which if you could include in your reporting, I think it’d be really good. I’m not only wearing this hoodie because Nicole sometimes refers to me as Professor Hoodie, but because it’s a charity thing, which is for local businesses, local restaurants that have been hard hit in order to help the people who are working there. So anything you can do to help people if restaurants are closed where you are or indeed to encourage people to get takeout and so on, is something that will be a really good thing in terms of helping people survive the next few months financially as well as in terms of public health. And with that, I’ll just get straight into the questions.
MODERATOR: All right, great. And as you are answering those questions, I’ll check in with Dr. Bloom again. And if this is a vaccine related question and we can just hop back to that when Dr. Bloom is on the call. First question.
Q: Hi, thank you. First, I think we all want to know what you think about this new variant. But my personal question is and I’m sorry this ask for a sound bite on a very complex topic, but what would be at the very top of your list of what we absolutely must do to prepare for the next pandemic? Thank you.
BILL HANAGE: Good Lord. The next pandemic. You know, we have a pandemic to get through already. I think that probably it is a very general thing but learn from mistakes because we have made mistakes. We have made a lot of mistakes. We have failed to put in place a bunch of no regrets forward planning in which we say if these things happen, then we do this and, you know, learning from previous experiences. Instead, we’ve been in a situation where we have been arguing and where we have allowed ourselves to be caught in a bunch of reversals, a rudderless pandemic response, basically internationally. So that’s a global issue. And I think that a global state of preparedness for the next pandemic is something that we should work towards. And the first thing to do there is to acknowledge the mistakes that we’ve made in this. I think that’s fairly straightforward and important. The other thing that I would add, and I think you all will understand where I’m coming from in this, it has been tremendously difficult in terms of those reversals dealing with the struggle in terms of maintaining public communication and scientific communication, including the trusted sources that you can rely upon to give you the best, most up to date information about the state of the pandemic and are capable of changing their mind if and when scientific evidence changes. So I think that sort of thing would be tremendously helpful as much as anything else. Also, public education level help. But there’s that old line, I can’t remember the old line. Barry may be able to remember it properly and where it comes from, but it’s like, before the pandemic hits, everything will seem like an overreaction. And after it, everything will seem like an underreaction. And I think that we’re probably seeing that right now.
Q: Thank you. And about the new variant?
BILL HANAGE: So the new variant, I mean, I will start by just giving a little bit of my background information about it and then we can get more pointed questions. So the new variant, or to give it its proper name, B.1.1.7. That just refers to the particular part of the further genetic tree in which you find it, was identified last month in the southeast of the United Kingdom through genomic epidemiology, which means that the United Kingdom has been doing an amazing job sequencing a relatively huge proportion of its infections, around about five percent. And this led them to identify a cluster of over 100 infections which were anomalously closely related. It was just weird to see a group of infections that are so closely related and also quite different from the other circulating viruses. And a bunch of features about that, which I’m sure we will discuss later, including the fact that one of the mutations within this variant actually makes it easier to detect using standard testing has led the authorities there to be able to track it and estimate its rate of increase as being substantially larger than the average for the virus. It has a number of important features, including, it has a large number of mutations, not a single mutation, but a large number of them, 23 additional mutations in comparison over the kind of background. And these are in regions that are thought to be important in terms of interacting with the human host and possibly the immune system. And as a result, this is the reason taken together of why we are considering this variant to be of concern. And there is a lot of things that we don’t know about it. And I’m happy to sort of talk about what they are. But I will comment that the state of knowledge about this is rapidly evolving. And that was not an intended pun, but the information about this is rapidly evolving. But I can tell you that what we know now.
MODERATOR: Are you all set?
Q: Yes, thank you very much.
MODERATOR: Welcome Dr. Bloom. Do you have any opening remarks that you would you like to say really quick?
BARRY BLOOM: No, thank you. Apologies for being late.
MODERATOR: It’s all right, considering you are supposed to be off today, we appreciate you being here. Next question.
Q: Yes, thank you. Here in Kansas, the vaccinations in nursing homes start next Monday. So I was wondering if you could fill me in on should everyone in nursing homes get the vaccine? Or do we know at this point that there are some people who should not base on their underlying conditions? And once people get vaccines in nursing homes, is it safe for family to come back in again? Or do we need to wait longer, wait until family members get vaccines, et cetera?
BARRY BLOOM: Terribly good question. As far as I am aware, the intent is to take people at highest risk and protect them with the vaccine, and those are people with the same kinds of predisposing conditions that people worry about. And as far as I’m aware, there are no limitations on who should get vaccinated in nursing homes, provided that someone can provide a signature indicating that they understand what they’re receiving. So I don’t think there’s a concern about that. I think the issue of when people can visit will probably vary from place to place, regulations, as far as I’m aware, from the CDC. But once people are vaccinated, I think everyone has to recognize even if they’re ninety five percent protective and Moderna was less than that in people over age 75, we’re still going to have to be very careful of bringing people who might be transmitting virus with asymptomatic infection into any place with vulnerable people, whether it’s nursing homes or hospitals. So it means people being tested, people wearing masks. And obviously, if everybody is vaccinated, it reduces the chances of any transmission. My guess is most nursing homes will be cautious and until the people that want to visit after two shots and are found to be unlikely to be infectious, they will be cautious about bringing visitors back in. I would also point out that the vaccines are not just for the residents, but also for the people who serve in various capacities within nursing homes, which I think is a really good recommendation that maintains both safety and some degree of equity.
BILL HANAGE: I would add to that that nursing homes are an area where the consequences of interruption are so great that there’s going to be some time before. We will not be clicking our fingers and returning to normal with vaccination. In fact, that’s a general point. And I would think that what Barry said was incredibly important because there is not a silver bullet to deal with this. Instead, there are multiple interventions. And one of the most important is a vaccine, but it’s not the only one. So if you have the vaccine and masking and other interventions, then we can gradually start to move from the situation we’re in now to a better place.
MODERATOR: Are you all set?
Q: Yes, thank you very much.
MODERATOR: Next question.
Q: Nicole, thank you. Gentlemen, thank you as always. Dr. Hanage, I’d like to start with could you go into some more detail about this new strain? I mean, you talked about 23 mutations detected so far. Is that 23 new strains? 23 mutations in the new strain?
BILL HANAGE: It’s 23 in the new variant. I’ll call it a variant because I think that to call it a strain, we require more details about characterizing it in its properties. But they are all 23 within this single lineage. And that’s one of the things which makes it look, frankly, unusual. It leaps out like a sore thumb. The reason I did it is that you can look at a virus and you can basically estimate how many mutations you expected to have based on the amount of time that has passed since the outbreak began. Because this is what’s called a molecular clock. You assume that the virus accumulates mutations at a specific rate. However, this we’ve estimated that rate for SARS-Co-V-2, this particular variant has about 20 more than you would expect given the time when it emerged and when it was first detected. It was first detected in the middle of September. It is currently responsible for around 60, 70 percent of new cases in the south east of England. So that’s a very rapid increase from the point when it was first detected. And that, together with these large number of mutations, eight of which are mutations in the spike protein, which mediates attachment to the receptor. And there are a couple of deletions there as well. These are taken together with the rapid increase caused to be somewhat anxious about this and its properties, which, as I said, are still being defined. It is an open question as to why this variant has accumulated so many mutations. Since it was detected, it has continued to accumulate them at the normal rate. But the excess suggests a period of time in a different selective environment, meaning not the normal transmission between normal individuals that has been responsible for the great majority of the pandemic. Some of the characteristics of the new variant are shared in common with long term chronic infections in individuals with compromised immune systems. And that is one hypothesis for what might have happened. Ordinarily, you would expect selection in that environment for a variant of the virus, which does very well within the host and does not transmit. And so that’s just one of the things which is still not understood in we’re trying to figure out what happened. But it certainly suggests a period of time in a different selective environment, but what that was exactly, we don’t know.
BARRY BLOOM: Maybe I could chip in question that a lot of people are asking, but you haven’t yet asked, which is the question of whether the mutations in this new strain suggest that the virus will be able to escape the immune responses generated by the vaccine. And the answer is, of course, one, nobody really knows that’s predicting something that hasn’t happened. As I understand it, they have tested this new strain with serum from people who have been vaccinated and or animals either way and shown that it is perfectly capable of being neutralized by neutralizing antibodies to the standard vaccine spike protein. So that’s very comforting. I think the other thing that’s comforting is because the vaccines are targeted at the region of the spike protein or at least the the spike protein, a region of which is required for binding to the host cell receptor. The virus has relatively little wiggle room to make mutations to escape antibodies, because if they do it too dramatically and cleverly, they’ll escape antibodies. They’ll also escape being able to bind to the host cell receptors and they’ll compromise their ability to get into cells. And one of the striking things about this mutation is that one of the places in that mutation appears to have been in the binding site that actually increases the binding that may contribute to why this is having a better survival effect. If the mutation was one that compromised finding antibody but also compromised binding to the cell, it wouldn’t survive very long in the competition of other strains. So there is a constraint on how wildly this virus can mutate to be able to escape antibodies. Someday that might happen. But it doesn’t seem likely early on. And another reason why that is true is that there’s a big difference between when we make a host immune response, and we treat someone with a monoclonal antibody. An example, measles virus is neutralized by essentially serum from anybody in the world. We take serum from anywhere in the world, ass it to measles virus, there’s an antibody in there since almost everybody had measles that will neutralize the virus. Any single monoclonal against the appropriate antigen will produce a mutant in a week. And what that says is that even if one piece of the binding site is mutated, you have antibodies to other parts of the binding site. So the probability of having mutants that escape all the various antibodies, high and low specificity and affinity of escaping a whole range of antibodies that every human being makes, is remarkably low. Very different than would be the case if we made only one antibody to one determined. So the hope is that the vaccines will work for quite a long time. There is a likelihood someday that this will lose the ability of the vaccine strain to induce neutralizing antibodies. And the beauty of these new virus vaccine platforms is with very little effort, and my guess is the work is already underway, people are putting genes from the new variant into the platforms so that if it did seem to be more resistant to antibodies generated by vaccines, they would have in the icebox vaccines against the new variant strains that are worried. And that’s something that could not have been done without the new platform. So there is an awful lot of thought going into trying to keep these vaccines updated can be as effective as possible.
MODERATOR: Next question.
Q: Thank you for this conference. I have two questions. The first question is a follow up question to Dr. Bloom’s answer. So you said that basically the new platform will enable us, basically to upgrade vaccines very fast and create the new vaccine, which are active against the mutations. But if a new vaccine is created, that’s set to go through all the testing stages, like a toxicology effectiveness again? Or is already approved for further utilization? And the second question is, there is a lot of emphasis on vaccines, but I wonder if the governments and the pharmaceutical companies should also invest a little bit more on drugs, given the fact that the vaccines will not be available to the population for at least one year to come. So I’m wondering why they didn’t come up on a vaccine with the drug strategy to protect people who cannot be vaccinated in the next month. And also, I was told but you can confirm that drugs can not only prevent the disease, but they can prevent infections. So they are a little bit on a more advanced line in the protection against coronavirus?
BARRY BLOOM: I think I can answer to some extent the first part of the question, I’m not sure I understand fully the intent of the second part. The first question is, if there were a variant that antibodies generated by vaccines were less effective against, would you have to go through the whole rigmarole of thirty thousand people tested in randomized controlled trials for a period of time as the virus is perhaps more threatening by simply updating the RNA to cover the new variant strain, or if it’s an adenovirus vaccine and it’s ever proved, that you could put the new spike protein into the new platform for adenoviruses. The answer is, I don’t think that has been formally discussed and agreed to by anyone, the FDA would be the one that has to decide. But we have a very good precedent. And the precedent is there are influenza strains that arise, as you know, every year, quite different strains, so that very often the vaccine worked last year or two years ago isn’t going to be effective against the new strain that comes from China or Australia or elsewhere. And the FDA has dealt with that by saying if all the production procedures are identical to the ones that have worked for the previously approved vaccines, then with minimal safety data showing that the new construct for the new strain is as safe in in vitro experiments and has the right properties in safety in animal experiments, it can simply be added to the list of new vaccines for flu without going through enormous amounts of human randomized controlled trials. So I would expect in the case, if there were a variant that was less affected by the vaccines against the current strain, as long as the RNA platforms and the companies did the same things, they would have very little difficulty in getting rapid approval to put them out. On the second question. I don’t know if I understood the question, how do you protect people while we’re still taking an enormous amount of time to roll out the vaccine to everyone? And at the moment, I don’t think we have a way to do that. There are compounds that have reported chemical structures that are reported to compete for the binding site similar to antibodies. They haven’t been in clinical trials yet. We don’t know anything about their adverse effects or how well they would work compared to antibodies. And I don’t know of any other drugs that would guarantee the people not able to get a vaccine would be protected, a priori.
Q: Well, just a short, follow up question. Actually, I mean, I’m in touch with a few researchers in the US and Europe, which are developing the drug against the community, and they are judging I think it’s in the phase two of the trials and it looks quite good. The thing is that governments are not putting as much money on drugs as they did on vaccines. So if you have less money, you have to invest more time to develop something. So I was wondering if you feel that the government should invest as much in drugs.
BARRY BLOOM: I can’t speak for your government. I can speak for our government. There is, in fact, a significant increase in investment for drug development at various levels of preventing infection in preventing disease and preventing death. And thus far, we haven’t seen an awful lot that looks particularly promising in animal models. So you may have access to information of a drug that is more promising than anything that I know about. But as I like to say to my students, I do vaccines, not drugs.
Q: OK. Thank you.
MODERATOR: Next question.
Q: Thanks very much. I have two questions, the first one is whether either of you have an opinion or a take on the approach that ACIP has taken to vaccine allocation in the United States, where it seems like they’re trying to both balances limiting deaths and limiting the spread in the choices of two groups that they make. Is that a good approach you think they’ve taken just in general, or how should vaccine allocation be done?
BARRY BLOOM: Let me ask Bill to comment and then I’ll comment.
BILL HANAGE: Yeah, it’s an interesting one. There’s always the issue that arises with any new vaccine of whether or not you vaccinate the people most at risk or the people who are most likely to be doing the transmitting. And that decision is being made at the moment within the context that we are not altogether clear, although there is some evidence from Moderna when they went to give the second dose as to whether or not the Moderna vaccine is able to prevent transmission infection in the first place as well as developing disease. But we don’t actually know necessarily very well for the mRNA vaccines, the extent to which it prevents the development of severe disease or the development of transmission. I suspect Barry knows more about that than I do. Obviously, if you have a vaccine which can prevent transmission, then it makes more sense to give that to people who may be doing a lot of transmitting than it would to give a vaccine that does not be very effective preventing transmission. So ACIP is trying to balance that. I suspect Bernie has more insights into what’s been going on in their thinking. I would point out, however, that over time, it’s quite interesting to note that the individuals who have been most at risk and the characteristics of the communities that have been doing most transmission have changed quite markedly. I mean, if only because of the fact in the spring it was the high-density populations in the Northeast that were most severely affected. But that’s because that’s where it happened. It’s not necessarily that high density populations are more likely to get infected. And so you need to be thinking about a number of these issues as you’re trying to roll things out. But at the moment, it’s just a question of most vulnerable and most likely to be involved in transmission and the interaction between them. And then I’ll look at hear what Barry has to say and look forward to being educated.
BARRY BLOOM: Let me just start by saying, you know, this is a really vexed question. You have a limited supply of a vaccine that has the potential to keep people from dying because both vaccines have been shown to have dramatically improved protection against severe disease. In one of the trials of a slew of people with severe disease, only one was in the vaccine group, for example. So the challenge is how does one equitably distribute that? And I would say these are really hard decisions. I think the CDC came up with a fair set of rather general recommendations. Clearly, the category number one, the top category was the most vulnerable since 40 percent of all deaths are in people over 75 years of age. Clearly, that is the most high-risk group that was targeted. And the second is while people who work in hospitals to deal with COVID patients do not, because of protective equipment, have the highest death rates. If they get sick and they are getting sick, the hospitals can’t function and we’re back to where we were to bend the curve because people, as we know now in the Midwest, people are beginning to talk about how to set out priorities of who gets to get a hospital bed and who gets sent home to die. And those are things that I would never imagine we’d have to contemplate. We are contemplating that now. So protecting hospital staff was why everybody and I think every state has agreed with the first category. The one disagreement after the ACIP meeting was one member of the committee who looked at the hospitalization rates for people 65 and over versus 75 and over. And they’re about the same. And his objection only was that the sixty-five-year old’s and over should have been included in the first group. So that seems to me a quite reasonable set of arguments. And I think the basis for the CDC or the ACIP was that we just don’t have that many vaccines to expand initially to that large number of groups. The more difficult challenges come when you go beyond that to the issue of essential workers, and that’s a much more arbitrary decision than an age cutoff. And so that’s been defined as people who work face to face directly in contact with people who may be transmitting HIV. And that’s, again, people who work in hospitals and health centers at the first line that are before even individuals know whether they’re positive or not, are likely to have contacts. And then obviously balancing those people to prevent them getting infected is the people who are likely to have the most severe illness if they do get infected, which was the comorbidity argument. People of a younger age group with comorbidities. Every state that has an adviser, two things; Massachusetts has an advisory committee on vaccines, which I have to say is one of the most extraordinarily inspiring groups of people I’ve ever worked with, people from religious groups, mayors of a town heavily burdened by COVID, representatives of minority groups and underprivileged groups and districts and towns that are burdened with infection all across the state.
And these are hard issues to debate. And I think that good faith and the listening and the willingness to think through how to decide our priorities is very inspiring to me and my scientific colleagues. And we’ve learned a great deal from that just listening to what the needs are in different communities. And one of the recommendations for lower groups has to do with a social vulnerability index that has been created, that has been proposed for consideration by CDC, that takes account of the increased vulnerability of crowded and economically disadvantaged and often racially increased groups. And at the same time, we have data that shows which districts in the state have the greatest burden as of this week or last week to disease, and a melded picture has been put together to when vaccines come into any age or other category, that 20 percent of those would go to that group that is regarded as most vulnerable. So that all I’m trying to suggest is deciding who gets vaccines first and second is really an emotionally and intellectually very grinding decision. And the experience that I have, if you bring people of goodwill and different perspectives together, you make a better decision. And I am stunned that the majority of states in the US do not have advisory committees of scientists and Lehmann’s and public officials actually weighing in on that. And I don’t know who’s making the decisions on priorities in those states.
BILL HANAGE: I’m going to echo that and I’m going to just point out something which is, I think, a story which could do with more reporting, which is kind of remarkable. Barry just mentioned the Dakotas and the fact that they’ve been getting to the point where really horrific clinical decisions of the kind he mentioned, who’s going to be given a hospital bed and who’s going to be sent home are being made. North Dakota is currently fourth in the nation among states for per capita mortality. And almost all of that happened since the start of October. So this is a place which has been aware of the virus, which actually witnessed what happened in the northeast and in the south over the summer, and has still undergone a very rapid surge of infections and has gotten to the place where it is now. I’m staggered that that happened, and I’m staggered that it has been allowed to happen in various parts of the country. And then I’ll shut up and talk about other stuff.
Q: I did have a follow up question, which was wondering if you had any advice for us as reporters in describing the effectiveness of the vaccines that come up here, as it’s said, ninety-four-point one percent effective, and then people push back on Twitter. What does that mean? What’s the difference between saying they’re effective versus efficacious, for example? And how should we report that? And, you know, should we be pointing out that the people who are in these trials were wearing masks and social distancing? It’s not like they were running around and diving into pools of COVID-19 to test them.
BARRY BLOOM: That’s a really tough question. These are really very tough questions. So in the world of reporting vaccine efficacy and effectiveness, a distinction is made and a valid distinction between vaccine efficacy as defined in randomized controlled trials, and vaccine effectiveness, which refers to real life, real world ability of vaccines to prevent whatever the endpoint is, infection or disease. A classic example that makes it clear of a vaccine against typhoid. That was tested in a major vaccine center on college students in the United States that was found many years ago to be 85 percent effective. It was then put in the field in Thailand, where it was found to be 65 percent protective because these people were just in a different state of health, different state of nutrition, different state of exposure than healthy young college students in a country that doesn’t have or see typhoid fever. So the trial results are efficacy data and effectiveness data is what we will learn once this vaccine is put out and there is tracking of who gets the vaccine and what percentage of them over time in the real world. And we will learn that there’ll be variations in effectiveness in different communities that will be somewhat different, I hope not very different, than those in the trial. But we don’t know until it’s actually put out into the real world. Does that help at all?
Q: That’s helpful. I just need to know how to think about it. Thanks very much. Sorry to take so much of your time.
MODERATOR: Next question.
Q: Hi, can you hear me all right?
BILL HANAGE: Yeah.
Q: OK, great. So I wanted to ask, some people are suggesting giving one dose of the Pfizer and Moderna vaccines instead of two so that double the number of people can get vaccinated. So what are the possible risks and benefits of doing this? And what is your opinion on whether or not it should be done?
BILL HANAGE: I’m very curious to hear what Barry thinks about this. I do have my own thoughts, but you can go first.
BARRY BLOOM: OK, you want me to go first? I’ll stick my neck out. We’re in a circumstance of a major problem and an enormous skepticism about vaccines. We have real life data on over forty-five or fifty thousand people who have received either of two of these vaccines and what the effect is of prime immunization and a boost. And we know in childhood vaccines that one shot doesn’t do very well. It does something. And we know that if you gave kids boosters at the appropriate times and age, you expand the number of antibodies producing cells, you expand the diversity of antibodies produced, and you expand the affinity, the binding activity of antibodies with boosters. So if you were a vaccine company that wanted to prevent liability and wanted to protect as many people as possible, you would optimize the conditions under which you put the vaccines out. And the companies have done that with different times for boosting based on empirical evidence or a good guess rather than real data, whether twenty-one days for the booster, twenty-eight days. In one of the trials, there is evidence of partial protection between the priming dose and the boosting dose, suggesting that the vaccine was effective on people who were asymptomatic and didn’t develop disease over the three- or four-week period that was being studied. We have data on the effectiveness for about six months, five months of the two shot vaccines for both during the trials, and those are the only real data we have that would tell people this is something that we can predict. If you’ve got protection for six months, you probably have most of your protection for a year. We don’t know anything about how long or how strong the immune response would be from a single vaccine dose.
BILL HANAGE: Absolutely.
BARRY BLOOM: And if scientists start guessing what the evidence should be, as opposed to building on evidence, it may save more lives in the short run. But then we come into a very sticky problem, which is when it wears off, how will we know it wears off? We know getting someone back for a booster shot for any vaccine twenty-one or twenty-eight days later, is going to be one hell of a challenge. If we give one shot vaccines now, and then decide at six months, it isn’t working very well. And the people who thought they were protected went out into crowded places and are now coming down, A, we will inform the public that the vaccine didn’t work and that people who take the vaccines are not really being protected. And when you try to find people six months or a year later, you’re not going to find them. So on purely scientific credibility grounds, I would go with what the data we know about that we’re explaining to people that we’re confident about will provide a certain degree of protection with a certain degree of risk. And I wouldn’t speculate on scientific grounds of what might happen if we have a single shot vaccine. I think it could be very difficult six months or a year from now if we find that it doesn’t work very well. And the last point I would say is that I think people don’t always appreciate. Everybody gets the same vaccine, but the duration of immune responses in individuals for any vaccine varies extraordinarily widely. It’s a wide curve from people who fall off from the Corona SARS virus in 2003, for example, some of them have antibodies that lasted a year or two and others had antibodies from the same vaccine at 18 years later. And there’s no way to predict who’s going to have an antibody that persists and who not. So I would think on scientific grounds, you want to maximize the effectiveness to protect people for sure as best you can, and also to protect the credibility of the vaccines so that they don’t fail and crash six months to a year.
BILL HANAGE: Yep, I mostly agree, I think it’s a question that it is reasonable to ask, but it’s an empirical question as to how effective a single dose would be for the reasons that Barry laid out. The problem is, if we assert that it is going to be more effective, that depends on some assumptions about how effective it will be and what it will do, which are not at the moment grounded in scientific evidence. We have evidence that a vaccination, one dose followed by another twenty-one days later provides a certain amount of immunity. We don’t have evidence for one dose without the full dose 21 days later, in the absence of that evidence, I think that’s problematic. However, collecting the evidence perhaps in the trial is not an unreasonable thing to do. But once we have collected the evidence from the trial, then we would be in a better position to be able to make those kinds of recommendations. And as Barry said, it’s hard enough getting some people in for one vaccine dose. And once you start saying to people, well, maybe you don’t need two vaccine doses, then a certain proportion of people will not take up the vaccine dose in the first place. And so a lot of this has to do with public health messaging and preserving confidence within the vaccines.
MODERATOR: Do you have a follow up question?
Q: No, I don’t. Thank you so much.
MODERATOR: Next question.
Q: Thank you for having me. A couple quick questions. Both of them are about pursuing population level herd immunity through vaccination. The first is about children. So just from a crude number’s standpoint, if children and teens make up some 20 percent of the population, I’m curious how the US would ever approach 70 or 80 percent vaccine coverage that would be desired to push toward herd immunity. I’m curious whether your understanding is that realistically, we really won’t ever reach these levels until children are also being vaccinated or if I’m miscalculating in some way. Second related question is just about the speed at which society would need to pursue herd immunity through vaccination. And you commented on this a little bit, but I’m curious, as we go into 2021, if we were to approach 30, 40, 50 percent vaccine coverage across the country, if people are skeptical of the vaccine and they’re dragging their feet, is there a valid concern that immunity could even sort of wane in those who have been vaccinated before the virus can really be thrown into the ground? I’m wondering if there’s a speed factor here in terms of getting everybody covered quickly.
BILL HANAGE: And I think the first comment I would make about this is that I think it’s extremely unlikely that we would be able to eradicate this virus. We have only successfully eradicated one virus, which had a particular set of properties that made it amenable to eradication, and that’s smallpox. We have been struggling with polio for decades, actually, one of the reasons of vaccine effectiveness the Barry was talking about, but I won’t get into here. So I think that in reality, we have to accept that it is not likely that we are going to be able to eradicate the virus. However, we should be able to get to a point where we are going to be able to live without it, you know, markedly damaging our lives or leading to surges which damage health care or large excessive mortality. That, I think is what we’re seeking to achieve. And that will start to be achieved when we start getting up to a reasonable fraction of the population. You said 50 to 70 percent. I mean, those are I will point out, relatively, it’s not that they are wrong, but the results of the simplest models, it may be a little bit lower than that, somewhere around 50 percent that we would need to vaccinate to achieve sort of effective vaccination levels of immunity before we were able to go about our lives without the risk of catastrophic outbreaks of this. I think that the question of waning immunity in groups which could lead to potential resurgences and indeed whether or not infections within those groups are like they were before, because it may well be the case that with waning immunity, you can be infected, but very unlikely to have mild symptoms is going to be the sort of thing that we’re going to be studying for quite a long time to come.
BARRY BLOOM: I agree with everything that Bill said. Let me take on the children’s issue. Children represent something on the order of one percent of all deaths from COVID and a smaller percentage than any other age group of disease. So in contrast to influenza, where kids and old people are the major victims of that disease, there is some lesser urgency of getting children vaccinated that might otherwise be. Second point with respect to kids is kids cannot give informed consent, so the idea of testing vaccines on a population that doesn’t know what’s happening to them and that’s not given any consent, but depends on parental consent, who represent a population of adults that have a fair amount of skepticism about all vaccines, but particularly a new one being tested on their kids. The decision was made, and I support that decision. And I testified in front of ACIP at an earlier meeting, that I don’t think that you could test a vaccine that wasn’t shown to be safe and effective in adults for the first time in children without knowing that and if I were a parent, I would have a lot of concerns about doing that. Having said that, the minute that that vaccine was approved as being as safe and effective as we know it could be and knowing that there is many children dying or almost as many children dying, even though that’s a small number of COVID, is with influenza in current years, I would be and am keen to have trials begin on kids and they are beginning from both of the two vaccines we’ve heard of. And my guess is from the other vaccines as well. And there the problem is a little complicated in that kids are not adults. They don’t necessarily respond either to adverse effects or protective immune responses as effectively as adults. And that means that there are age groups at which the vaccine may have to be used at a lower dose. And that requires trials to ascertain whether as you drop the dose of the vaccine to ensure safety at younger and younger ages, you get the same degree of protective antibodies, which by itself means it will take more time to work out the conditions to vaccinate kids. So that I think that everybody is keen to be able to bring the vaccines down to protect children, both to protect them per say, and since we know kids can transmit, protect them from transmitting for extended family members with whom they may be in contact. But I don’t think you test an unknown vaccine in terms of safety and effectiveness on kids until you’re pretty sure it’s not going to do them any harm. And I’m pleased that both companies have started to think about testing kids bringing the ages down from 18 to 16 in the case of Pfizer and will bring it down to 12 in the case of Pfizer, a little higher in the case of Moderna, but carefully bringing it down to lower age groups. In terms of herd immunity, something like one hundred and sixty million doses of vaccines a year are given to kids and adults in this country. We know how to get the vaccine to kids a lot more effectively than we do to adults. So if, like Bill said, this becomes a an endemic infection that we need and immunity doesn’t last lifelong, which I think with an RNA vaccine, is extremely unlikely, it means that we’re in a circumstance that we will need to be vaccinated every year, every two years, every five years. We don’t know. And that means we could put a safe and effective, appropriate dose childhood vaccine at the appropriate stage in childhood and get that eighty to ninety-four percent of all kids, which we do for other vaccines. So that’s why I think kids have to be last on the list for testing an unknown vaccine.
Q: Thank you.
MODERATOR: We have one more question, I believe. Could you both stick around for about another five minutes or so, would that be possible?
BILL HANAGE: Yeah, I can have another meeting, but I can wait for five.
Q: Hi. Thank you so much for taking this call. So there was a strong recommendation made in both of the advisory committee meetings to use a blinded cross over design in order to both meet the quote, Ethical concerns that volunteers in the placebo arm be able to get the vaccine and at the same time maintain the blind. The FDA has not required this of the companies and has left it for the companies to decide what they’re going to do. And neither company is apparently adopting that methodology. And I’m wondering if you have concerns about loss of blinded data because of this, or do you think that we can get enough information with how they’re approaching it?
BILL HANAGE: Personally, I don’t think I know enough about exactly how the trials were designed in order to be able to comment on this. I would make the comment that hopefully, we have enough information already to be making good decisions.
BARRY BLOOM: So the concern has to do with the fact that anyone in a clinical trial is free to withdraw from a clinical trial. That is autonomy, one of the cardinal ethical values of experimentation on human subjects. And with the availability of vaccines that now and increasingly will show effectiveness, what happens if you’re in a trial? The trials are blinding. You don’t know whether you’re in the placebo group or you’re in the vaccine group. And if you’re in the placebo group, you know you’re at risk. And so there is every rational reason for people once there’s a safe and effective vaccine without knowing their status in the current trial as vaccine volunteers to pull out of the trial and say, I want a vaccine that’s 95 percent protective. And they would have the right to do that, provided they are within the right category of phases to be able to receive the vaccine, and that’s been one of the recommendations that has been made that, yes, if you want to withdraw from the trial, there’s no reason that you should be allowed to go to the head of the line before people that are at higher risk of dying or have comorbid conditions are essential workers. You would be able to do that. I think there are two things going for the efforts to keep people in trials. Even in a crossover trial where everybody has vaccine, you lose data only if people withdraw from the trial. And so the intent here would be, yes, you would have the ability to find or get another vaccine as long as in the trial we know what you had. But we would like to follow you for two years, which would add enormous amounts, more data if you have chosen to get a vaccine and if you are committed enough, as all these volunteers were, to risk your life, to take a vaccine for the benefit of knowledge and protecting everyone else, many of those people will stick it out if they’re not in high-risk groups and we will be able to get long term data. What the proposal for the crossover studies would have been, this could have all been planned in advance, anticipating the problem so that the statistics would have been there, enabling people at the appropriate time to cross over and take a new vaccine and stay within the trial, rather than have people randomly at random times withdraw whatever time they felt like it. It’s unfortunate, but that proposal was not on the table, as far as I’m aware at the time that these trials were originally designed. But I think the major point I would like to make is whether people withdraw from the randomization and get another vaccine or get the vaccine dose and unblind themselves. It would be really great if they stayed in the trial. That will enable us, if everybody at that point would have had a vaccine, to learn something more quickly about the safety of the vaccine.
Q: Just a real quick follow up, I mean, why not just require that blinded cross over now? Everybody would get the vaccine and as you said, we’d have enormous amounts of data that could be followed.
BARRY BLOOM: Right. So the answer to the companies is you have forty-five thousand people in the vaccinated groups and an equal number of people in the control groups they randomize, the companies are not privy to who they are and they would be absolutely no way, in a practical sense, to randomize forty-five thousand people while you’re trying to get everything else done on the trial. So it’s very difficult once the genie is out of the bottle to go randomize and deal with individuals out of a forty-five thousand group or fifty thousand group or sixty thousand group into two vaccine trials and actually get this done simultaneously. It’s just practically unfeasible. Could have been done in the beginning.
Q: Thank you.
MODERATOR: I think that’s it for our questions. Dr. Bloom, do you have any other comments before we close up?
BARRY BLOOM: No, I thank you for the wonderful questions. This is going to be a challenging six months, both because of the disease and what I would predict would be a change from a huge amount of skepticism to an increase in demand for vaccines that the supply will not allow to be met and pressures on every state government of people trying to find ways to get their sub-group preferential treatment to get vaccines, which is going to be challenging the integrity and credibility of the system, unless we’re absolutely open and transparent and stick to guidelines and not allow people to jump the line.
BILL HANAGE: Yeah, I would I think that’s a very, very, very great point that Barry’s made. I’m going to close with an observation that I obviously have a very good job explaining what’s happened with the new variance in the UK. But I want to point out that given that it’s already in Australia, Italy, Iceland and Denmark, it’s quite probable that it is already in the United States as well. Those places which have protected it, all those that have good systems for this kind of surveillance, which the United States does not have, really at all. So I think, in fact, if something like that had arisen in the United States, it might be quite hard to detect, depending on which part of the country it inhabited. So I’m sure we can expect more of it in the coming weeks.
This concludes the December 22nd press conference.