You’re listening to a press conference from the Harvard School of Public Health with Barry Bloom, the Joan L. and Julius H. Jacobson, research professor of public health and former dean of the school. This call was recorded at twelve thirty p.m. Eastern Time on Thursday, January 28th.
MODERATOR: Dr. Bloom, how are you doing?
BARRY BLOOM: Still here.
MODERATOR: Very good. I sent you a few questions. I don’t know if you had a chance to take a look at those or not.
BARRY BLOOM: I don’t think so.
MODERATOR: OK, if that’s something you would rather do at a different time, just let me know and we’ll figure it out from there.
BARRY BLOOM: You know, these are general questions, and the answer is every state does its own thing. It’s just crazy.
Q: The general consensus, right?
BARRY BLOOM: A general consensus, and I don’t know any way to fix it.
Q: Yeah. I also was curious about kind of walking, not detailed walking, but sort of walking through what the timeline should sort of be from, say, a raw material to in a vial. I don’t know if you have that level of detail.
BARRY BLOOM: I don’t have that level of detail. But raw material into a vial is probably pretty quick. They’re working on essentially an assembly line basis. And that means that the ability to make new increases in vaccine production is very limited unless they set up a separate production line, which is the equivalent of a whole technical factory for producing viruses. So, as you know, Pfizer BioNTech has shut down delivery in Europe so that they can create a new factory production line to increase the supply. With the existing facilities, it’s very difficult. And one of the delusions that I think people have is the idea that the Defense Production Act, which is a way of, for example, taking manufacturers of automobiles and having them make respirators, taking electronic equipment from one place to another, you can’t do that with vaccines. This is a really complex business. And something that it took me a long time to appreciate is something called “know how” you can patent “know how”, but you can’t write it in a textbook. This is a really complicated business that requires highly skilled people that you can’t go by with a Defense Production Act to make vaccines tomorrow. Very highly specialized, what you can do is provide reagents and materials, glass piles, syringes to speed things up. But we are limited to the expertise of the two companies and hopefully a third soon that has developed over the last many years the expertise to produce vaccine. But therefore, it’s interesting that Sanofi, whose vaccines did not produce good immune responses, has offered to help Pfizer to use their production capacity to convert it to producing RNA vaccines. And again, they would have the experience. But otherwise, we are stuck with a very limited and inevitably limited, highly technical, highly expertise and highly safety directed business of producing vaccines.
MODERATOR: I am going to interrupt really quickly because we kind of got a jump on the call before everybody got on. So I’m going to just start the call, if that’s all right, and then maybe we can pick up where you stop. All right, everybody, welcome to Harvard T.H. Chan School of Public Health media call for January 28th. Dr. Bloom, to have any opening remarks?
BARRY BLOOM: Two comments. Viruses are really complicated and producing vaccines is really, really complicated. So if I can’t answer all of your questions, it is because it is complicated and probably behind beyond my expertise.
MODERATOR: I think that’s just fine. Nobody can know everything. Great, Dr. Bloom, thank you very much. Should we pick up then with did you have any other things to say for vaccine manufacturing and those that topic, do you have any questions?
Q: I also just wanted to follow up with the idea that I know that there had been warnings about the potential of exactly the things we’re seeing now, which includes wasted doses as well as the black-market potential. And, you know, the question is, looking at it from that becoming a reality, are there solutions to that or are we in what someone called a Darwinian stage where everyone is just going to be able to get it if they get it and don’t if they don’t?
BARRY BLOOM: For reasons that I don’t fully understand, the process of distributing vaccines makes very little sense in the case of what I would call a national emergency. If you look at the front page of The New York Times about which parts of the country are in the greatest risk for COVID, it’s the whole bloody country and you would expect a nationwide response. But in a country where every state has their own insurance, their own health policies, their own health situations, each of them has to do it differently. And we have not had up until now, terrifically great central government coordination. And I worry starting where we are now, how you could do it. Even in my state, which is a relatively enlightened state, you can’t go on a website in the state to find out when you can get an appointment at which site, you can find out what sites there are for vaccinating. But since vaccines are delivered by the companies to the sites, not through the state, you have to get into each site to get an appointment. This is insanity. There should be a central registry that says I’m seventy-five years of age or over 65 and I have morbid conditions, whatever. Where can I get a vaccine and when? And they should be able to put you on a list. And logistics and computers are very smart. This could be handled, but that’s not how things are being done in the States. Occasionally a state like West Virginia and Alaska can take control. But in other states you have districts and towns that have their own health boards. And it is very difficult to coordinate, which I think is a real tragedy and a hindrance to knowing exactly where the vaccines are needed, exactly how many doses should go, which vaccines they have, the facilities for the refrigeration. I don’t think the huge amount of vaccine doses are being wasted. I think they’re sitting in their freezers because they don’t have enough places for vaccinators or setups to enable people to go to the places to get vaccinated. So it’s really an organizational problem, not that the vaccines, as far as I know, are running away and being thrown away.
Q: Thank you.
MODERATOR: Next question.
Q: Hi, Dr. Bloom, thanks so much for doing this. Looking ahead to the Johnson and Johnson filing, could you help us give a layman’s definition of how the Johnson and Johnson technology, the vaccine is different from the Pfizer and the Moderna ones that we could explain to people what the difference is? And as a follow up to that, any concern that people will think, well, I’m getting two doses of this vaccine, so it’s got to be better than getting just one dose of Johnson and Johnson and maybe explain the variants in those methods.
BARRY BLOOM: I don’t want to give a long disquisition, but it’s a fantastically important question and the answer is pretty complicated. So starting with your first question, what’s the difference between an mRNA vaccine and the recombinant adenoviruses vaccine? RNA is what codes for proteins and the protein that codes for is the major protein in the virus and in the RNA vaccines, you get the RNA and in a delivery system that activates an immune response pretty well and you make the antibodies to the viral protein that you make. You’ve never seen the virus. There is no virus. You can’t get sick from it or you can’t get virus from it. You can’t get COVID from it. You’re simply making the protein that ordinarily would be made by a company if you were getting a tetanus shot. And it’s best to do it that way. Extremely efficient to do it that way. And I think beyond most scientists’ expectations, the production of antibodies that neutralize the virus at the ninety-five percent level and protect against disease is better than anybody expected. So this turns out to be not only quick and efficient, but it is effective. The strategy for the Johnson and Johnson and the AstraZeneca Oxford vaccine is again a well thought out novel strategy is we know that you have a virus like an attenuated strain of adenovirus, which is not able to cause disease, but it is ordinarily a normal respiratory pathogen. What would happen if you remove its major antigen in protein and replace it from the spike protein of the coronavirus. Exactly the same principle. You want to generate an antibody that neutralizes and T cells that recognize the major antigen of coronavirus 19. And in this way, you stick it into a non-disease-causing virus that you will recognize as a virus. Recognize the COVID protein in the virus and make an immune response to that. So the target in all of these cases is the same. It’s a portion of the protein that is what’s essential to enable coronavirus to attach to and invade your cells. And if an antibody can block that, then the virus can’t infect yourself, whether the spike protein is in an RNA that you produce as the antigen, whether the spike protein is an adenovirus that you recognize, and trigger is a good anti spike protein response or as a company called Novavax is doing. If you just take the protein and put it into a mixture of immune stimulants called adjuvants. The sole strategy is to get an immune response as big and complex as possible to the critical region on the spike protein that enables the virus to get into cells. And if you can do that, you can block efficient infection, and you can block, obviously, disease. So the strategy is how to get there is quite different, but the target is exactly the same. The antibodies produce can be measured in the same way. Do they protect against the virus getting into cells?
Q: So in Johnson and Johnson, they’re using the virus to get the protein into the cells to be able to repel it, but it’s not a virus that’s going to make you sick or virus that is in any way related to coronavirus?
BARRY BLOOM: You’re absolutely right. It’s a different virus. It is attenuated. It can’t grow and cause disease. But the way we describe all this stuff is RNA is a platform. Adenoviruses with foreign proteins is a platform and purified proteins with adjuvants is a platform. And what a platform is designed for is any new virus comes and you identify the critical target antigen you can clone by recombinant DNA into production of that antigen in each of the different platforms. So that’s why this has been so quick. The platforms were developed over the last 20 years, not just for COVID-19, but they were sitting there ready to go. Once you knew that the protein was the critical protein to get the virus into the cells, some labs and companies had experience with RNA. Others were with large AstraZeneca in Oxford and Johnson and Johnson and others like Novavax and Sanofi with protein in those platforms were sitting there waiting for a pathogen to come. And that’s why this is the vaccine production level unprecedentedly quickly, because it was all anticipated before the infection in the epidemic occurred.
Q: What about the possibility, as I mentioned, that people will look at this and say, oh, it’s better for me to get two vaccines from Moderna and or Pfizer as opposed to this one vaccine. What do we say to people about how one vaccine in this case could be just as effective as a regimen that requires two vaccines?
BARRY BLOOM: It’s a really important question, and if the J&J vaccine actually turns out to be a single shot vaccine, it’s going to raise exactly those questions, but in a different context. Which is the problem. The great advantage of the adeno vaccines, probably in addition to having a lower price, is the fact that they don’t require deep freezing at minus 80 degrees centigrade or minus 20 degrees centigrade. They can be kept in a refrigerator in your doctor’s office. The other vaccines can’t do that. So the ability to distribute the Pfizer, which is the most difficult, that requires really cold conditions and can only warm up at one time on a dose of vaccines for five hours. The Moderna vaccine that requires less cold, but still difficult. This is a vaccine like flu and like every other vaccine that can be distributed to every drugstore and every doctor’s office that has a refrigerator. That’s a huge advantage, and when you ask the question, where is that an advantage? There are two obvious places. One is in rural areas that do not have the infrastructure to deal with very cold vaccines. And the other is in those areas, in urban areas, with large numbers of people with high vulnerability, which is particularly black and brown, people who are difficult to access in any case, minus 80 degrees is not a common feature of inner-city neighborhoods. And so this vaccine becomes very much easier and accessible to get to the most vulnerable neighborhoods with high density housing. And that can be delivered the most easily. The question then is, are they getting the best that we could do? We don’t know the answer because J&J hasn’t published how effective their vaccine is. If it’s 90 percent effective, that would be fantastic, with one shot, I would have absolutely no questions about that. If it was 50 percent or 60 percent, and they had been able in their studies to show if they gave a second dose, it went up to 90 percent, I would say I would push hard to get them to do two shots like everybody else, because we want the level of protection to be as high as we possibly can. We don’t know the answers to that. The expectation is in the next two weeks or so, they will be able to reveal the data on how protective the vaccine is. And my understanding is they have done subsets in their volunteers with one shot in subsets with two shots so that we should know whether one shot is as good as we need to get high levels of protection.
Q: Thank you so much.
MODERATOR: And I have a link I want to put into the chat, if you would like to see, it’s to the New York Times. I have a very nice explainer for how the different vaccines work too. Next question.
Q: Thanks very much. I am wondering, I know nothing’s been set yet, but I’m sort of wondering if you have thoughts on, I guess when basically it will be time to update the vaccines based on whichever’s with mutations, the virus picks up as it goes? How do you know if it reaches a certain threshold? Like what can you extrapolate from looking at Sarah in labs against variants to know when it might be time and what sort of like regulatory steps do you think, I guess tweaked vaccines should have to clear, if any.
BARRY BLOOM: Wonderful question. And this is a question that I am somewhat obsessed about, because if the mutations occur to the extent that the virus is no longer recognized by immune responses developed against the initial strain. That’s a big worry. And so the comfort is, I think, a couple of things. There’s basically one site on the virus, the so-called receptor binding domain. The combine to the host cell receptor, the virus in the cell. So the good news is, there are not an infinite number of mutations, I don’t think that can constantly be coming up and escape immune response because most mutations that seek to avoid the immune response will actually no longer bind efficiently to the host receptors. And in fact, we know that the only mutations that initially arose were ones that found better than the original Wuhan virus. So they were looking for, this is the Darwinian question, the battle of the virus is not the struggle for the fittest between humans and the virus. It’s which variant of virus can compete against all the other viruses. And the first ones that arose initially in England turns out to bind better to the receptor. And that may be why it seems to be transmitted more efficiently. You get a limited number of hits that cause disease because once it hits, it makes an infection that can produce the disease. What’s interesting about that English strain is that the antibodies work better on that, because they bind to the same site and the immune response appears to be absolutely as or more effective against that first.
What’s worrisome is strains in South Africa and Brazil and probably elsewhere have mutations that clearly, in my view, have been selected by the immune response where the virus is trying to escape the antibody response to the receptor binding domain. And the data as of the moment, I think are interesting and from a journalist’s point of view, not going to be easy to explain in the following sentence. First, what they’ve looked at is serum or plasma from people who have recovered from the natural infection, so called convalescents serum, to see what their antibodies see when you run them by a panel of mutants or variants. And what we learn is that some people who have recovered react perfectly well and, in a test tube, neutralize viruses containing the spike protein as well in the mutants as they do in the wild card virus in the original Wuhan virus. Other people who’ve recovered and we’re talking about maximum 40 for people who’ve been looked at in one study, six people in another study. These are enormously detailed studies of many artificially made mutants. So we don’t have huge amounts of data. But the data suggests that there are some people who react at least tenfold, less well that have recovered from their virus infection, but they react tenfold or more less well, against some of the mutants like the South African and Brazilian mutant.
So against the same mutants, you have a range of human responses that range from absolutely as neutralizing as it would be for the original virus to a hundred or more-fold less efficient, which would worry you as to whether it was good enough to protect. All of the neutralization data is done in the test tube. We do not know how that translates in terms of protecting against disease. We will learn that from further studies of people who have either recovered or get reinfected. And when they’re infected, they’re very tiny numbers of demonstrated infections after a primary infection. And to make that clear, that means you have to have the RNA sequence of the original virus and the RNA sequence of the second infection to be sure that you really got two separate infections. And that’s been done in a very limited number of cases. And in those cases, we don’t fully know what the answer is, but it looks like in some cases people just never made antibody in the first infection against the S protein. They just didn’t do it. And by the second infection, they did, and they got over it. Whether some of them actually are found to no longer be able to protect against variants, and in the second infection, they are infected with variants, we don’t know, not yet. And more importantly, are there people who have been vaccinated, are infected with the equivalent of the South African strain or the Brazilian strain, where we know there is a diminished ability to be neutralized by convalescent serum, diminished ability to be neutralized by monoclonal antibodies. The question is, are those people more susceptible to disease? And the good news, which makes it hard for journalists, is human immune responses are enormously heterogeneous. Some people can see the same protein and see different parts of it. Some people can see none of the parts of it. And in the variants, what I would expect to see is a huge variation in people who see different parts of the protein that give you protection and others that don’t in the variants. And we’re going to have a whole range of susceptibility to the variance. It will not be everybody is resistant, and this is a so-called escape, or everybody is susceptible.
So with that, we know none of the data beyond the test tube level as to whether in people infected with the variants. They make enough antibodies to different parts of the spike protein or different antigens in the virus protein that are protective even that they lack the particular variant determinants. So they don’t see the variant well, but they see other parts of the molecule well. We don’t know that yet. That’s a real hope. And there’s some expectation there are more than a few patches on the S protein that enabled the virus to be neutralized at more or less efficiency. So when people say there is still hope that the vaccines will protect against the variants, what they’re saying is even if you knock out a few sites on the viral protein, there may be other sites that people in their heterogeneous immune responses still make good antibodies to that will be protective in vivo, not just in vitro. And there’s just a huge amount we don’t know yet that is testable in the serum of people who have now been vaccinated. And so I am hopeful that the hope is that even if some of the sites are mutated, there’ll be other sites that are protected.
If not, the third part of your question is the companies are already making RNA vaccines, for sure, against the mutants that I’ve talked about that seem to be the best at eluding immune responses that have three mutations in exactly the areas that neutralizing antibodies bind to. And the expectation of the companies is it’s just another RNA and they could make a booster shot containing those new variants that should be as good at generating immune responses as the original vaccines. And in this case, they would be boosting the original immune response, but targeting the response to the variant antigenic sites. And if that’s the case, they should be back to 90 percent of the new mutation. And I go back to the first comments that I made. How long can this game of mutation continue? Can it be infinite? Can the virus keep changing all of the sites all of the time? And the answer is, it will. But there’s a limited amount that can change that will enable it to bind to the host. And that’s the restriction on the number of variants we have to worry about. We don’t know what that number is. It’s not infinite. So maybe we need only one new kind of booster if there are triple mutants that are not well seen by the immune response, that would be fantastic. Everybody could get a booster and that could be done with any of the platforms. The booster could be in the adenoviruses, it could be in the adjuvant in protein and will almost certainly be in the messenger RNA vaccines. And as Tony Fauci likes to say, we have to stay one step ahead of the virus and we can now anticipate the kind of mutations that are arising. We can make a vaccine that will get ahead of.
Q: Just a really quick follow-up. You were saying it seems fairly easy and the companies have said this to sort of tweak, I guess, vaccine design to better suit whatever mutations emerge. Is that so? That’s the design question. But is it easy to switch over manufacturing to that newer recipe almost, because that’s obviously been our hurdle so far?
BARRY BLOOM: In principle, yes. It’s just a different party with a few mutations in the RNA. There’s no particular obvious reason why it should be more difficult to produce or to generate an immune response in someone injected with the RNA. But we don’t know that until it’s tested.
Q: Thank you so much.
MODERATOR: Next question.
Q: Hi, thanks for taking my question. My question is in regard to the vaccine rollout. Minnesota is doing this pilot program where they’re doing like a lottery system where people enter online for appointments for limited doses of vaccine. Do you see that being something that we do in the future? What are some pros and cons of that?
BARRY BLOOM: So, I have read the National Academy report on how to think about prioritizing vaccines during this period of time, their availability is limited. I’ve read the Advisory Committee on Immunization Practices at the ACIP, the committee that advises the CDC on all vaccine recommendations. And I have a pretty clear view of what sort of ethical principle should pertain, and the first ethical principle is every life counts. And if you look at the mortality rate of COVID-19 and you believe preserving life is the great target or goal of vaccines to keep people from dying, then we know that the mortality rate was COVID-19 sharply increases over 50 years of age, greatly increases over 65 and it’s highest in people over 70. So if the goal of implementing a vaccine program is to save lives, this explains why the priority in most states has been people at greatest risk of dying or having serious disease that times intensive care units and hospices. And that is very strikingly clear in tables from the ACIP presentations where age 75 and over, it’s a ten-fold greater risk in that group for dying, for hospitalization followed by death than in any other age group.
If you’re asking the question how do you keep society open during a pandemic, when the answer is we can’t suffer the shutdown of hospitals, not just for COVID, but people with heart attacks, strokes and automobile accidents and every other acute condition that hospitals have to address. We know from a year ago and 2019 to last year 2020, there was an equal number of deaths, what we call excess deaths, deaths from lung disease in hospitals, because people either didn’t go when they had acute conditions, or the hospitals were so tied up with COVID they wouldn’t treat them and people died. So from my perspective, what you want to do is save as many lives as possible. And every life count, and that includes people at high risk, which would be vulnerable communities, African-Americans and Latinx individuals who on the scale in risk for disease is higher than most people in other parts of cities and countryside, rural populations where they don’t have access to high health care. So these are the considerations that every crazy enough, every state has to evaluate. Maybe the most efficient way is to have a lottery, but it will not save the most lives that much the statistics in the models have already shown. It eliminates the question of why is it that I get, for example, as a member of the advisory committee in the Commonwealth of Massachusetts, I get a lot of letters. Why aren’t grandparents in the top group? Why aren’t type one diabetics? Why only type two diabetics as a comorbidity? Why isn’t this group why being that group? That’s the one question solved by a lottery. But that’s not the critical question. The critical question is what’s the best way to do three things, which are the ethical principles, one is beneficence, the best for the most people, which is how do you save the most people’s lives? The second is, how do you do it in the fairest way, so everybody has more or less equal access. And that’s done to prevent those that are rich from having these benefits that the poor do not. That’s a way of categorizing people with disease age over 75 age over 65 people with various diseases. That’s one way to ensure fairness. And the third is equity, how to compensate for the increased risk of poor and disadvantaged and vulnerable populations by making sure they’re not the last to get vaccines, but among the first in any of their categories. Those are the reasons why I think a lottery where anybody can line up and get their vaccine is not the fairest, doesn’t do the best for the most people because it doesn’t save the most disease. And almost certainly the last to sign up for a lottery would be the disadvantaged population.
Q: And what about for phase two? What if we just did a lottery system for phase two, like we already vaccinated phase one, A, B and C. So we made sure, let’s say, people over the age of 55 are vaccinated, those with comorbidities and essential workers and health care workers for the rest of the population, would it work better then or not? And why?
BARRY BLOOM: So you can open it up to everybody. This is a debate, for example, many states have opened things up over age 65 because they like the over 75’s, have very high rates of about five-point seven-fold greater, in the 75 it’s about tenfold greater risk. The problem is we don’t have vaccines. And once you say, OK, we’ve opened up the criteria so everybody can apply, what you end up doing is frustrating a lot of people building unrealistic expectations that if I’m over 65 or if I have two comorbidities, I can line up for a vaccine. If the states don’t have the vaccines, it creates a lot of unhappiness, angst and disillusionment with the inefficiencies. Whereas if you target them to a specific group and you can get the vaccines out and in some states, they have been able efficiently to use 90 percent of what they’ve got within those categories. So as in the case of West Virginia and Alaska, other states are not able to deliver them even to the restricted groups that would have high priority. That’s an efficiency problem, not an equity problem. And my sense is every state has to decide what it can live with. I don’t see a great advantage opening up the categories when you build expectations, and you don’t have the ability to deliver the vaccine. And I would say I think the companies are close probably to their maximum capacity. So their hope is without any production failures, which is always a problem. Every state is going to get an X number of vaccines every week. That’s not going to double, triple and quadruple until spring. So building expectations that will miraculously have great scores of new vaccines from somebody’s freezer, they don’t exist. Is that helpful?
Q: Yes, thank you.
MODERATOR: Next question.
Q: Yes, Barry, can I ask your views on the antibody cocktails developed by the likes of Regeneron in any other. They have been taken up an awful lot in their EUA under for mild to moderate COVID-19, but they’ve got some new data on the uses, prophylactic immunization that’s just been published. So what’s your views on the usefulness of those therapies, particularly, for instance, in immunocompromised individuals and what barriers do you foresee in their uptake?
BARRY BLOOM: So it’s again, it’s a somewhat complicated answer. So let’s start in a world that has only the original strains and virus from the Wuhan or the English strain, which appears to be equally well neutralized by the monoclonal antibodies. I don’t think the data are clear precisely when they are most effective, but it does appear from the earliest symptoms, if you can reduce virus replication with the monoclonals that are very efficient at neutralizing viruses in the test tube, you may be able to avoid severe disease and death. And obviously one needs more data on that. That seems a new addition to the very limited armamentarium of Remdesivir, which doesn’t seem to be all that terrific. And dexamethasone is really just keeping the worst of outcomes possible in the percentage of individuals. So if you could start with the monoclonals earlier on, that would be a good thing. And they have huge disadvantages. One is they’re difficult to produce in vast amounts. They take large amounts of protein given intravenously and infusion centers, and nobody wants coronavirus patients going to infusion centers that are used mainly to treat cancer patients. So you have to set up a separate facility to safely be able to do intravenous multi-hour injections of large amounts of these proteins.
And finally, the biggest worry is we now know that at least the South African variant is largely resistant to at least one of the monoclonals in the Regeneron copter, totally resistant, also resistant to one of the antibodies in the Pfizer vaccine. So when you have variants that are resistant to the single monoclonal, how long will it take to be resistant to both? And the reciprocal question is, if you’re selecting with a single antibody against the single site, you can almost guarantee over some period of time you were selecting for a mutant to resist that antibody and you will select for an escape route to the one site that remains. So there are plenty of worries with the idea of the antibodies. Clearly, a new monoclonals could be made that we’re recognizing the sites in the new variants just as the RNA vaccine people are doing. But that’s a big problem and it will not lessen the cost. So I think using them while you can, while we’re not dealing with those variant strains that we know already would be resistant to the existing monoclonals, that strikes me as a good idea if it prevents people from getting acutely ill and dying. Once those mutants come, if they do, I would be very cautious in how to use those monoclonals if in fact they don’t neutralize and only select for resistance to one of the other, determine. Does that make sense?
Q: Yes. I think the Regeneron, that’s got a subcutaneous formulation, so that’s how I make things a little bit easier.
MODERATOR: Are you all set then?
Q: Yes, thanks. Thank you both.
MODERATOR: Perfect. Next question.
Q: Thank you, Dr. Bloom, for doing this call. You know, I cover education for USA Today and, you know, we’ve seen a lot of discussion about teacher vaccines potentially being the linchpin to getting more kids back to in-person learning. But, of course, teachers are not being prioritized in all states. Should they be from a public health perspective? And if so, do you have any ideas on how that could be better coordinated?
BARRY BLOOM: You know, it’s an absolutely fundamentally important question that really challenges both the data and the ethical issues. What we know is everybody in the public health business understands not having kids able to have it in class learning is exerting an enormous price on education, learning, socialization. The price that kids are paying for this epidemic may be ultimately the greatest crisis of anyone, and it’s not measured just in economic terms. On the other hand, kids are the least likely to have severe disease, and we know that kids can be infected. We know that they can transmit, although less efficiently than older age groups. So the concern that you raise is if we could vaccinate teachers, could we open schools? And my personal view is that would be absolutely fantastic to be able to do that. The problem is that would not meet the criteria that the people at greatest risk for death and severe disease. Most schoolteachers are not over 75, most are not over 65. Most don’t have multiple comorbidities, although I would expect some overlap.
So if the focus is on saving lives, then as you’ve seen in most states, school teachers don’t score the top if you focus on creating conditions for society to function. I would put schoolteachers at the very top with people who are facing levels in emergency rooms and hospitals, and that’s a tradeoff that every state seems to be able to have to make if and when we have enough vaccines. I would hope every state would get past the number of people aged 75 and 65, which is not an insignificant number. But then in the next group, very much this is what we call essential workers, which include at the top of that list I would put schoolteachers, but that depends on having enough vaccines. And as you well know, there are a lot of schoolteachers that have to be vaccinated. So, again, the question is, you start with elementary school teachers, where the biggest damage in compromise is education and socialization are occurred. Or you start with teenagers and high schools and junior high who are most likely because of their social habits or college students, most likely to be the major transmitters of infection. And that leads to the fundamental issue. Are you trying to preserve life and present those at highest risk for death, or are you trying to preserve an important social value like schoolteachers, or are you trying to prevent transmission? And we have very little data on any of the vaccines, on how effective they are on preventing growth of the virus in the lives of parents, and whether even if you’re protected against disease, you are protected against transmitting infection. That’s not yet known. So that’s another argument for saying till we do, we know we can protect against the disease and death by taking vaccines to the people in nursing homes and conjugate settings that we know is the highest risk for dying. It’s terrible, and I really feel for the governments that have to make that decision.
Q: And one quick follow up. There are some groups that are calling for waiting to reopen schools until we vaccinate all children as well as all teachers. Is there public health data to back up that kind of, you know, the sort of universal vaccination schedule considering we don’t have a vaccine for kids?
BARRY BLOOM: So, as you know, on everybody’s list, because children have the risk of getting severe disease and dying quite different, for example, than in the case of influenza, where it’s children and the elderly that are higher, the highest risk for death, vaccinating children has been the lowest priority. The companies are now reducing the age groups, the original age group was 18 to 55. All the vaccines are now testing people over 55 because we have to know if they were in age 65 and 75, which is, you know, don’t generally do as well as younger people. So that’s an important thing to find out, and the data from Pfizer and Moderna to everybody is really is they seem to be producing as much neutralizing antibodies in the elderly as they do in people at the younger ages, which is fabulous. So that’s very good. Getting down from 12-year old’s and younger is more complicated for a couple of reasons, one of which is we don’t know whether the dose is given to adults are appropriate for giving to younger children. And that means more studies and more trials to reduce the dose to get the maximum immune response with the least amount of toxicity. I don’t believe kids are simply little grownups. I think there are risks to adverse effects will be different and the companies are going to have to run trials. Maybe not three hundred thousand people or thirty thousand people trials, but they’re going to have to figure out doses. And we have so limited doses they want to get the doses that they have and to people to save lives.
MODERATOR: Are you all set?
Q: Yes, thank you.
MODERATOR: Next question.
Q: Thanks Dr. Bloom, and one final question for you. And thank you so much for the time. On the variance part of it, we know that Moderna at least is working on that booster and of course, the others are likely to follow. What do you anticipate the timeline for manufacturing and production to be as a result of that? Should we expect sort of a similar slow ramp up or are our parts of the process already expedited at this point?
BARRY BLOOM: I think the way they’re thinking about it is a booster shot for people who’ve already been vaccinated. So the timeline would be dictated by whether the variants or the mutants that are less well neutralized by the current immune response is produced by the current vaccines when they become a problem. And they are not yet a problem here. And with a little luck, they may not be a problem. While they are resistant to some extent and some of them in individuals tenfold or more, all of them seem and the limited studies that have been done able to be neutralized by some level in most vast majority of convalescents serum. So it may be that you can have a variant which is highly resistant, but there are other signs that people’s immune responses, which, as I indicated, are highly heterogeneous with different people, see maybe enough to get you through. If, for example, you have a tighter of one to ten thousand and the variance is neutralized at only ten percent, the level you still have a level of one to a thousand that is guaranteed to protect and neutralize. So just having a neutralizing mutant that is less well neutralized doesn’t mean that it is totally unable to be neutralized. And that’s what people have to go look at people who’ve been vaccinated with the current vaccine. How many of them remain susceptible to disease and are they all mostly protected, in which case, even if the companies have the booster shot, they may not be necessary. Whether that will be the case or not, how well the new variants will fare in competing with the other viruses remains unclear at this point. And we don’t have many in the country and we don’t have the testing ability to screen for variant viruses, which I dearly hope the new administration will allow. We only have about six thousand viruses that have been completely sequenced. So we don’t even know what’s here at the moment, whether it’s spreading or not, whether the new variants, when they get here, they appear to be here, whether they do well or not well and whether we have to worry about them. So there’s no quick timeframe that the see, until most people are vaccinated with the existing vaccine.
Q: Right. My question was more geared towards the manufacturing of those vaccines and whether or not it would require sort of a whole new ramp up and time timeline or if it would just follow along, if it would just be easier to do and quicker to do, because it would be a tweak essentially.
BARRY BLOOM: In terms of the FDA, I think the process would be very much like influenza, which is every year we have new flu vaccines and every year we have new strains of influenza. They do not have to run thirty thousand trials with each new vaccine. They have understood that if they make it by the same process that worked for the older flu vaccines and don’t change the process significantly, the FDA will accept it if they share that each lot is safe and some level of effectiveness. So the expectation here is they wouldn’t have to do very large trials if they simply substitute a variant protein into the current existing process. What I worry about is whether the production capacity is such, whether they would have to set up a new factory or a new production line to make additional vaccines for the variant or whether they have to shut down an existing production line to make their own vaccines, which means less of the old vaccine in order to get a start on the new vaccines. Production of vaccines as I started this conversation is incredibly complicated and the only expertise and facilities are the ones we have.
Q: Thank you.
MODERATOR: We have a couple more questions, Dr. Bloom, would you be willing to stay for a couple extra minutes?
BARRY BLOOM: OK.
MODERATOR: Thank you. So that the reporting on monoclonal antibody treatment is confusing. And I believe you talked about monoclonal antibodies earlier and I got a phone call, so I missed that. Apologies that this is a repetitious there was something out this week that suggested that using the antibodies could interfere with the COVID-19 vaccine uptake. Do you have an opinion on who, if anyone, should be seeking monoclonal antibody therapy right now?
BARRY BLOOM: Sorry, could you repeat the two parts of the question?
MODERATOR: Sure. So she said that there’s something out this week that suggested that using the antibodies could interfere with the COVID-19 vaccine uptake. Do you have an opinion on who, if anyone, should be seeking monoclonal antibody therapy right now?
BARRY BLOOM: OK, that’s pretty straightforward. The vaccine is designed to protect people who have not been infected, to generate an immune response that will keep them from getting sick. That’s the end point of what we know. The monoclonals work with people who have been infected and early in infection to keep them from getting sick and dying. It is possible you could use the monoclonals to protect normal people, but the supply and the expenses such that will not replace vaccines and I don’t think I see any obvious reason why the monoclonals, which are designed to prevent serious infection, would compete with vaccines. I don’t think there are enough of them or the infusion part to deliver them that would make it something that everybody wants to take. I think it has a very special place. It could be very important in that place, but it doesn’t replace in any manner, shape or form vaccine.
MODERATOR: So that special place that that monoclonal antibodies should be used for is somebody who thinks that they have been infected and, in this case, would not also have been given the vaccine recently.
BARRY BLOOM: I’m not sure that I would agree with the second part, if they’ve already been infected, looks like they’re having a bad course of getting sick, I would have no question about giving them in addition to what they have in the vaccine, because, as we’ve said, the vaccines are 95 percent protective against disease, but there’s still five to six percent. And as I started by saying, there are some people who receive vaccines, have got infected very small numbers. They just never saw the spike protein in their immunization for whatever reason. And so those are people who would benefit from the monitoring. So I would still focus in on people who are infected with the risk of getting sick or have clinical symptoms that you want to protect. That’s where I would use the monoclonals. And if they had the vaccine, they shouldn’t get sick. But if they do get sick, the monoclonals might, in fact, help.
MODERATOR: Next question.
Q: Thank you for doing this, I have a question about the roll out of vaccines in the developing world. Obviously, it hasn’t really started yet, but I’m wondering what we can learn from the experience in wealthy countries, particularly in Europe at the moment with the kind of hiccups in production and distribution. Should we, given that timeline, seem to be moving back in wealthier countries? Is that bad news potentially for the rollout in poorer countries that seem to be sort of next in line? I guess I’m wondering what we can learn for that sort of broader picture.
BARRY BLOOM: Thanks. So what we have, what we can learn, I believe, in watching particularly the situation in Europe and the low and middle income countries is that WHO much criticized in the past, particularly by our country was out in front saying that the inequities of this world are such that if somebody doesn’t think about how they get vaccines into poor countries, this virus is going to wreak havoc in the world. And if variants emerge in Brazil and in South Africa, we know they will get to the first world. And we know that not everybody wants to take a vaccine. So until we can get control, as we did for smallpox, for measles, everybody in the world having access to vaccines, there is a risk that this disease will continue to come back and cost lives and fortune. They proposed a mechanism by which the rich countries would contribute money or vaccines to enable an impartial and internationally representative group of people, foundations and otherwise, to assign vaccines a percentage. The expectation was to provide 20 percent of the population needs to be able to keep the hospitals, the medical communities and the most vulnerable, giving them access to vaccine. Not one hundred percent for everybody, but enough to not have the health system crushed by this virus. What’s happened there? Rich countries have put in contracts. Canada has contracts for six times the entire population of Canada, six times more vaccines promised to Canada than their bloody total population. I would guess the US is not quite that high, but we also have no extra contracts. Israel has a forty five percent already have contracted with vaccines and they are individually contracted. So it is now the law of the jungle. Every country that wants vaccines rather than having it dealt with through an international agency designed to represent the fairest way to provide the best, in fairness and saving lives and essential functions is that dissipates, and it isn’t over yet. And I’ll come back to that. It means every poor country has to pay their resources at a premium, which is what Israel pays, what Indonesia has paid a high price to be able to get vaccines from the existing companies. And that puts the poorest countries, the countries, ninety-two of them at the end of the line. That’s a very sad global circumstance. The variable that has changed is the Biden administration has indicated they will return to WHO, they would like to contribute to the COVAX program, and there are two ways they could do that.
One is to commit money to enable countries or WHO to buy the vaccines or actually GAVI is the administrator for this, the Global Alliance for Vaccines and Immunization, which provides children’s vaccines to all the poor countries in the world, a wonderful organization. They are in the business of contracting to be able to distribute vaccines that are provided through products. What they need is vaccines or money to buy vaccines. And what the US’s role will be remains in the four days of the new administration, unclear. I would like very much to hope that there would be enough funds contributed not just by the rich countries, by the middle-income countries and even possibly poorer countries to say we want access to vaccines and what, we don’t have big dollars to contribute. We would rather contribute to an international effort that is fair than having to pay a premium of six times the price to get vaccines at a later time from somewhere that may not be the best vaccine available. And as you can tell, some of the countries are buying vaccines that have not yet been through phase three trials, have not yet been published, have not yet been evaluated for safety and effectiveness. We have no idea. But China and other countries are producing. That’s a worrisome sign that could lead to great trouble and compromising the integrity of the whole vaccine process. If some of those vaccines may be in abundance and at low price, turn out to be not safe or not effective. So it’s in everybody’s advantage to have, I believe, an international distribution of vaccines and a national effort, as we did with smallpox, to be able to get vaccines to every part of the world to get rid of this pandemic.
Q: Just the quickest follow up, do you think the fact that we’ve seen such troubles rolling out vaccines in rich countries is a bad sign for poor countries, even if only because they’re, as you said, next behind the rich countries in line?
BARRY BLOOM: At the moment, it’s not a good sign. I would hope that the difference is confounded by the Brexit exit because the UK has lots of vaccines and they have contracted vaccines, that must be very painful for the Europeans from Pfizer that are made in Belgium. And the Europeans are really unhappy that Belgium produce vaccines, are going to the UK and Canada. And I understand their unhappiness that was to have been settled by an agreement that was interrupted by Brexit. I am hopeful on the world scene they would recognize the failure of organizing that and getting consensus of what the fairest way is to do internationally and would rectify every country on its own. I’m not optimistic.
Q: Thank you.
MODERATOR: Just this is maybe more of a legal or an IP question, but if pharma companies can license their products to other producers so as to increase their production, do you know if that’s a possibility or is it just not in their own best business interests to do that?
BARRY BLOOM: I think it’s a wonderful question. And my sense is that at least some of the companies would welcome that in the sense that from the beginning, the AstraZeneca Oxford adeno vaccine, was licensed to the largest vaccine producer in the world, which is the Serum Institute of India, which produces the majority of childhood vaccines in the world, really high class, high quality, high production capability. And they have agreed to produce the AstraZeneca vaccine at the concessionary price, 50 percent of their product would go to low- and middle-income countries. So there is no hesitation for some of the countries if they can be assured the production, quality and capacity is there, which is capable of producing significant amounts of high quality vaccines in any country with a commercial license. I gave a lecture to people at the University of Cape Town and had some homework for that lecture. I was stunned to learn there is not a single vaccine producer in all of sub-Saharan Africa. Now that there is no one to license the vaccine production to because the expertise and production capacity is not there. There is one vaccine company that does finish until it takes the vaccine made in an industrialized country and puts it into vaccines and vials and distributes it. That’s not the same as adding to the production capacity. So I would welcome that. I think some of the companies would welcome that. That’s not going to happen in the next six months.
MODERATOR: A follow up question.
Q: Hi, thanks for taking my question. Just a quick follow up. What is the assessment in terms of capacity for four potential producers who now no longer really have the IP licenses to produce? How much capacity essentially are we losing? And I’m talking about both in the developed and the undeveloped world. In the developing world, in terms of, you know, companies that clearly, they don’t have a license to go forward but may have the capacity. Do they exist? Are they marginal? Can you give us a clue?
BARRY BLOOM: It’s a terrifically important and valuable question. I really don’t pretend to know about the quality vaccine producers in low- and middle-income countries. I think it’s even hard to find out, for example, given the lack of published data of the quality and effectiveness of vaccines that we know about that are produced in large amounts in China. So you need to have data to be able to answer that. We know that there is a biotech industry in India. We know there are two vaccines in India. I mentioned the Serum Institute of India producing the AstraZeneca vaccine. There’s another company named Barra, and I cannot find out how effective and safe there are studies on in that vaccine, but they clearly have vaccine capacity. There’s another company called Asunta in India that has produced vaccines, but not COVID in the past. So there are reservoirs of companies that have produced vaccines for local consumption, whether they are technologically able to produce high tech RNA vaccines, whether they’re able to produce recombinant adeno vaccines, whether they’re capable of producing high level protein vaccines and complicated adjuvants is totally unclear to me. But in sub-Saharan Africa, what I can say is they don’t exist there. And I find that absolutely shocking.
Q: So then the real issue of MSF and others have basically advocated a waiver on COVID-19, that’s not really an issue, in other words.
BARRY BLOOM: I’m not an expert on the issue, but I know in the HIV realm, a number of years ago when Jeffrey Sachs was at Harvard, one of his fellows in a study on the question of whether African countries restricted the use of antiretrovirals in Africa and the result was striking. Thirty-one countries, only five, have ended agreement on the international trade and partnership agreements. The rest of them could do whatever they wanted. They weren’t bound by any agreement. The problem is the rest of them didn’t have the capacity either to produce the drugs or certainly a vaccine. So what we learned in that period is whether you were signed up for the intellectual property rights agreement or not, if you don’t have the capacity to make vaccines, you don’t have to worry about violating intellectual property rights. I don’t think that’s likely to be limiting in this case. There may be a couple of special places where you’d have to sign those rights, as India has done. But I would guess four places in sub-Saharan Africa, there are only a few countries that could make them. Places like South Africa or Kenya would be obvious places. And as you remember, that’s what broke the backs of the monopoly of the antiretrovirals when South Africa showed them the antiretroviral drugs producers who were so stigmatized by denying lifesaving HIV drugs, they dropped the IP issues and they enabled the drugs to be distributed in Africa, which was one of the great lifesaving events of my lifetime, making a completely lethal disease to a chronic illness that depended on that South Africa decision and the companies willing to forego the licensing agreements.
Q: Thank you very much.
MODERATOR: I think that’s our last call question for today, Dr. Bloom, do you have any final thoughts for us?
BARRY BLOOM: No, I’m always being stretched by your questions. I need to do more homework on international vaccine production capacity. And I hope to be more informative at our next meeting.
This concludes the January 28th press conference.