Coronavirus (COVID-19): Press Conference with Sarah Fortune, 05/21/20

You’re listening to a press conference from the Harvard T.H. Chan School of Public Health with Sarah Fortune, the John LaPorte Given Professor of Immunology and Infectious Diseases and chair of the Department of Immunology and Infectious Diseases. This call was recorded at 11:30 a.m. Eastern Time on Thursday, May 21.

Previous press conferences are linked at the bottom of this transcript.


SARAH FORTUNE:  I was just going to start by introducing myself. So I am an immunologist by training. And I wanted to just – I know my goal here is not to speak for very long, just extemporaneously, but I wanted to acknowledge what an incredible 10 days it’s been in COVID vaccine development and flag for you some of the interesting trends that are emerging from what I consider to be the four major vaccine stories of the last few weeks. And those are the Oxford chimpanzee adenovirus vectored vaccine, the Sinovac PiCoVacc vaccine, the Moderna vaccine, and then very recently, like as of yesterday, data from a DNA vaccine from Dan Barouch’s lab. And of those, I would say as I look at the data as presented, the two strongest data packages so far from the Sinovac vaccine and Dan Barouch’s DNA vaccine.

And it’s very both heartening, but there are some cautious notes in those data. So both of those vaccines did a good job in protecting against disease. So they put in – these are both in monkey studies, so they protected non-human primates against disease where their disease metrics were either frank clinical disease or virus in the lungs that they took as a quantitative measure of disease. But very interestingly, neither of these vaccines was nearly as protective in protecting against carriage in the nose or the throat, which I think you might think of as a metric for how well that vaccine might protect against transmission. And as we think about vaccines rolling forward, it’s a common paradigm in vaccines to have that some vaccines are going to protect against disease, but not protect against transmission.

And when we think about what we’re going to expect a vaccine to do in the COVID epidemic and specifically providing herd immunity in a population level, I think it’s a little bit sobering to see that while we may get protection against disease and so we’ll be able to protect people from getting sick, we may not get nearly as effective protection against transmission, which means that to protect the population, we’re going to have to be vaccinating many, many more people because we can’t rely on sort of getting to a lot of people and then having the epidemic die out through herd effects. So that was going to be my opening salvo. But I am happy to ask questions, our answer questions about anything you’d like to talk about.

MODERATOR: Alright. Looks like we’ve got a first question.

Q: Hi. Thanks very much for doing this. I have a question. I was hoping you could talk a little bit about the correlates of protection or correlates of immunity and sort of what those are, how immunologists determine what they are for a specific pathogen, and then sort of why it’s important to establish what they are or maybe also why it’s not super urgent in the grand scheme of things.

SARAH FORTUNE:  No, it is so urgent. And I love that question. It’s so dear to my heart. OK. So basically, if you would like to understand protective immunity or immunity generated by a vaccine, right, how are you going to do that? So the most definitive way is to give that vaccine to a whole lot of people, let them get naturally exposed and track disease outcomes and then measure the protective efficacy of the vaccine against disease.

So the problem with that, of course, is it takes a long time and you have to wait for disease outcomes. And those can clinically take quite a while to manifest. So it’s not a very efficient. And it is a very expensive way to test vaccines. And so what you would like is that some blood measure of what how well you’re doing that serves as a correlate of that protective efficacy or immunity. Which sounds like it’s simple, but it is much more complicated than you’d think. One of the nice things about this, actually there were two studies from Dan Barouch’s lab at the BIDMC that were published yesterday. He did the best work that I have seen thus far in trying to look for a correlative community because in one of these studies, they took non-human primates, infected them with COVID, let them go their natural course, and then re-infected them, so looked for who was protected and then looked for blood markers and really antibody markers of that correlate protection of protection against disease.

And in vaccine world, like a common correlate is the ability to take those antibodies and put them in a tissue culture dish and squirt in vaccine and see how well those antibodies prevents the vaccine from infecting those cells, that’s called neutralizing antibody like a neutralizing antibody titer. And so that would be what’s commonly used. It turned out to be a little more complicated than that. Antibodies come in different flavors and it seemed like if you looked at the flavor of antibody, you could get a more robust correlate. But the reason people are doing that is to try to improve the rapidity with which we can understand vaccine efficacy and similarly to try to understand when we look at population surveillance studies and see antibodies, whether that really means that people are protected or whether that just means they saw the virus, generated antibodies, but those antibodies aren’t going to help them in the future. Does that answer the question?

Q: Yeah, I guess like the definition or what you’re looking for in terms of establishing what the correlates are, is it both a combination of the mix of the antibodies and also the immune cells? And is it also like the quantities?

SARAH FORTUNE: Yeah. So it can be any of those. So, like a correlate does not actually have to be biologically related to the mechanism of protection. In this case, people, broadly people like correlates that are it seems like by biologically plausible mediators, protection like antibodies and then the titer of antibodies, like how much the quantity matters, the flavor of antibody and whether that antibody seems to have biologic protection in a dish, their neutralisation. They like that. The field – that doesn’t prove that those antibodies are actually what’s doing the job, but that those are the common things to look at. But honestly, if you’re like you gave a vaccine and somebody’s toe turned blue, it had nothing to do with the direct mechanism but it was a good predictor of whether that tracking worked, that would also be a correlative immunity.

Q: Got it. Thank you. 

MODERATOR: Great. Next question.

Q: Thanks so much for taking my question. I found that point about the kind of gap between or the difference between protection against disease and preventing transmission kind of in a similar vein to the last question. What do you, what exactly do you look at to get a sense of whether a vaccine is effective in terms of preventing transmission? And then secondly, in terms of why you highlighted those two particular data packages, Sinovac and from Dan Barouch’s lab, was that just related to the sort of amount of data produced or just specific things within relative to the Oxford vaccine or Moderna? Thank you.

SARAH FORTUNE: Yes, sure. So let me answer the first question about disease versus transmission. So actually in vaccine development, typically people focus on disease and then it’s only kind of, it’s typically with broader use that people begin to understand its effects on transmission because transmission is hard to measure experimentally or even in a small group of people.

And so it’s hard to get a handle on. But vaccines like the acellular pertussis vaccine or the meningococcus vaccine, MenB, they protect people against disease, but they do not protect against transmission. And actually a little vaccine fact here. So we used to use a whole cell pertussis vaccine that had some bad side effects or more commonly had some side effects and we switched to an acellular vaccine, so the whole cell vaccine did better against protecting against transmission. And then people think that the epidemic transmission of pertussis is now that switching vaccines, which protects against the disease very well, but is not protecting against carriage and transmission.

So, in COVID, people are trying to understand protective efficacy against transmission by swabbing the nose or the throat of these experimental animals. It is a poor proxy because we don’t really understand whether that, you know, there’s a lot that goes on between a virus in the nose and whether that virus is viable to be transmitted. But it’s clear that there is the effect in the lung are more profound than the effects in the upper airway from each of those studies. So the DNA vaccine, at least DNA vaccine studies, the Sinovac vaccine and the ad vectored vaccine study. And in terms of the comparative strength of data packages. Yeah, there were more data in the DNA vaccine and the Sinovac vaccine paper. And they more convincingly show dose effects and actually had a little bit better effect in the lung than the ad vector vaccine. In the Moderna vaccine.

I mean, you’ve seen what I see, which is, they gave the vaccine to 35 people. It was immunogenic, so they generated antibody responses. Their measure of efficacy that they reported was that the antibody titers was – so they measured antibody titers in 35 people and in eight people, a very small subset of people, they measured the more maybe biologically meaningful ability of those antibodies to prevent entry of that virus into tissue culture cells, so that’s neutralizing antibody. What they said was the titers were as high or higher than in people who had had natural infection, like the neutralizing antibody titers. The problem is that cohort studies of people who have had natural infections kind of range all over the place in terms of whether that’s good or bad. So there was just a recent study that said that only 3 percent of people who have that natural infection have high titers of neutralizing antibody. Seventy five percent have medium titers and 20 percent have low titers. So to do better than that, it’s not really clear how well you’re doing. So while it was hopeful that Moderna was immunogenic, it was a very low bar for them to cross.

Q: Thank you very much.

MODERATOR: Next question.

Q: Hi. Thanks for doing the call. I’m wondering, so, we’ve got news this morning that AstraZeneca, with their deal with Oxford, with the Oxford vaccine, they said they’re going to have vaccines, three hundred million doses ready by October. And I guess the question is really? What is a realistic timeline for any of these vaccines?

SARAH FORTUNE:  Well, normally it’s much longer than October. The world has the most experience with ad vectored vaccines and platforms, the manufacturing platforms that scale, I guess, are more robustly developed for those ad vectored vaccines. I do think you’re right to be skeptical though, because there are a lot of challenges with that scaling issue and then lots of challenges with packaging, delivery, the cold chain, you know, that whole downstream manufacturing process is really complicated and I think one should view those announcements with a degree of skepticism.

Q: Thank you.

MODERATOR: Next question.

Q: Hi. Thanks very much. This has been a fascinating discussion, so I have to apologize for changing the subject. But I wanted to ask you, the topic I want to talk about was about the reopening of states. And I’m wondering what you think about the different approaches that states are taking. Does it matter that I can go get a haircut in Maine and I can have dinner in Rhode Island and I can’t do either of those things in Massachusetts? I mean, what are the what are the risks and hazards of having such heterogeneity in states’ response?

SARAH FORTUNE: OK, let me give you two sides of the coin on that answer. The first is that obviously this is incredibly challenging for the states because there has not been coherent federal guidance. And so individual states, relying on the guidance of sort of their individual collection of experts, have to make the best decisions they can. And those decisions reflect both the opinions of their experts and honestly, the other pressures, economic, political pressures at play in the state.

And that’s hard for those states. I mean, that’s usually a level of scientific and economic, the integration of scientific and economic factors that normally occur in the federal government, not asking every state to make their own decision. And some of those decisions are going to turn out to be fine and some of them are going to turn out to be real misses. There are definitely going to be mistakes. And, you know, you can just understand that there are going to be mistakes that are policy mistakes. And I don’t want to necessarily say we know what those are. So, obviously like going out to dinner is different than having your haircut because I don’t think it is so obvious. I mean, except for things like nightclubs or bars or something that are highly dependent on close congregative behavior. But so some of those decisions will be policy mistakes.

And we’re going to unfortunately, we’re going to discover that post-hoc, but we’re also relying on individual people to then integrate these sort of guidelines about infection control in their own businesses. And some people are going to do that better than others. And some individuals in the community are going to abide by those better than others. And that’s – sort of how well people do at a community level really is going to determine the success of the reopening plans. And that puts a lot of burden on individual people.

Q: So is that inevitable, though? Or is there another way to do it?

SARAH FORTUNE: Well, certainly other countries have chosen different ways, so other countries have been much more prescriptive in how reopening happens, much more prescriptive, and have just been able to have a little bit better control over the points of transmission. Even in other countries though, the success or failure of those measures does come down to individual behavior. And so where you see individuals who make bad decisions, you know, those can really have – especially if they happen to, of course, be, you know, the super spreader, always works that way – then it really can have profound consequences on local dynamics.

Q: Do we even know which aspects of the shutdown were most effective?

SARAH FORTUNE: Which aspects. I think that viral transmission always depends on people coming together. So, any aspect of the shutdown that really limited people coming together, I think you can from first principles say that those were important aspects of limiting transmission. But if you’re asking did  the decisions about construction versus office workers versus restaurant, were any of those more important than the other? No, I don’t think we know that. We are left with very blunt tools and then trying to understand from that very blunt perspective how to make more fine grained decisions based on our understanding of how transmission occurs and what behavior looks like. But it’s a very imprecise science.

Q: Thank you.

MODERATOR: Next question.

Q: Hi, Dr. Fortune. If cases do go up and we need to shut down or restrict again, are there are there things that you think we’ve learned this time around that will allow us to do it better or more in a more targeted way?

SARAH FORTUNE: Well, I wish I had a resounding yes for you. I think we have, okay. There are resources that we have that are going to allow us to do better in a more targeted way, and that might be as good as lessons learned. So we clearly have vastly more testing capacity than we did when we had to shut down the first time. And by July, we’re going to have five to 10 times even more capacity at a state level anyway.

And so I think we understand that testing and testing on cases is important. And as we develop more and more testing capacity, what that’s going to allow us to do is not just test symptomatic individuals, but to test contacts of symptomatic individuals. And I think that our ability to do that will allow us to be smarter and then will allow us to understand where, through our contact tracing will allow us to understand where transmission is occurring. So that’s old fashioned infection control.

But old-fashioned boots on the ground epidemiology really help you understand where things are going wrong in a concrete way. So, I think that the fact that we’ve developed this testing capacity in a contract tracing that work will enable us as we see more transmission, and I think we should expect to see more transmission, will enable us to sort of track that down and react to it and be adaptive in our responses moving forward.

Q: And you said we should expect to see more transmission, which I guess, I guess makes a lot of sense. Is there one metric that you would think or that you’re looking at to see if we do get to a place where we need to reverse course?

SARAH FORTUNE: Well, I think I say I don’t think given where we are, where we don’t have – given the tools we have on hand, I think of the governors metrics are not unreasonable. And so those would be sort of percent test positive – of course that can fluctuate depending on how many tests you have available to deploy – but also your hospitalization rate and your ICU occupancy. Now, those are very again, blunt and they lag way behind what’s actually happening. And so, you know, to the extent that we can use our testing resources to get a handle on real time infection dynamics and then use serologic testing to do better population surveys, I think that that will be important.

Q: Good, thank you.

MODERATOR: Great. Next question.

Q: I got a follow up. I was wondering as well, we’re talking about mobility and and seeing more transmission because of people moving around more, I’m wondering if we’re actually able to see any difference in the rates of transmission from people changing behavior like wearing masks for one thing, maybe giving people a little bit more, you know, a little bit more space. I saw the the new Imperial College model came out saying that they’re basically doubling the number of deaths over a two month period because of increased mobility. But they don’t take into account things like mask wearing and testing, tracing also. So I’m wondering, it is maybe premature to to say but can we see impacts of mask wearing and behavior change on transmission? Do we know that opening up is going to cause the same level of infections as we saw before, you know, before we locked down?

SARAH FORTUNE: Yeah, that’s a good question. And I think you’re absolutely right that we should not – I mean, hopefully – we should not expect to see the same level of transmission before we locked down, because we do know, for example, from hospitals where the measures, so mask wearing, attention to surface hygiene, and distance, and symptomatic screening, really, really, really did a great job at limiting within hospital transmission. So people still got, health care workers were still at high risk to get infected from their patients, especially in the EDs and the ICU.

But those measures did a really good job at preventing health care workers from infecting other health care workers or infecting other patients, which is sort of a very contained example of a population that’s at high risk of transmitting among themselves. And so I think that – but it’s only in those pretty defined circumstances that I think we have evidence that we can limit transmission through these measures. And it’s just, you know, the cautionary note is health care workers are, of course, extremely motivated to observe all those safety measures very assiduously. And so, we as a normal people and the community should also be highly motivated to observe those safety measures assiduously to maximize their efficacy.

Q: Thanks.

MODERATOR: Next question.

Q: Hi. Good morning. Thank you for this conference. I would like to ask you a retrospective question that I always ask experts like you. I know that many pharmaceutical companies which are developing the research on vaccine, they are building their current research on the results achieved while they are doing research for a vaccine against the SARS outbreak in 2003. And I would like to know if we had the vaccine already tested on humans against SARS in 2002/2003, would we try to use it against the novel coronavirus or at least speed up the vaccine against novel coronavirus, upgrading the former vaccine? Would it make a difference actually?

SARAH FORTUNE: Well, it would make a difference and it did make a difference. So that vaccine research got pretty far along before people lost interest in SARS-CoV-1 and sort of let those vaccines molder on the shelf. But we learned a lot. So we learned actually about the complexity of the downstream process. So many of those vaccine efforts had a sort of interesting and concerning safety signal. So we don’t really have enough data out of our current vaccine efforts to, I think, make any confidence statement that we’re not going to see this time around. And the safety signal was that the vaccines, actually, sort of protected against viral take in the lungs, so the virus’s ability to infect the lung, but then they recruited the wrong type of immune response in a subset of animals.

And this is actually been seen with RSV vaccines and people. So, like it looks fine and looks fine, but a subset of people got the wrong kind of immune response or an immune response that looked a little bit more like allergy than viral protection, and then it made them really sick. And in the case of RSV, actually vaccinated individuals did worse than unvaccinated individuals just because of the numbers of people who would normally even get sick from RSV. So, I think we learned a lot about what to look out for and how to do this better. And I think if we had taken it all the way through and had a licensed vaccine for SARS-CoV-1,  we definitely would be trying it. But that wasn’t wasted effort.

Q: So, you’re saying that there wouldn’t be a chance that the vaccine against SARS-CoV-1 would work?

SARAH FORTUNE: No, no, no. There was a chance but those vaccines had a safety problem. So a safety problem that we don’t know if our vaccine is going to have yet. So, yes, it may be that we would have had a home run. But even what we uncovered in that effort is really helping shape our thinking about what are important parameters to be measuring in vaccine development today.

Q: OK. Thank you.

SARAH FORTUNE: You know, and I guess what the other thing I should say, it’s not as if you could use the vaccine necessarily to vaccinate for SARS-CoV-2 and really get good cross protection because your immune system is extremely, exquisitely sensitive to very small differences in the viral antigen that it’s using. And so your immune system can see the difference between A and B or A and A Prime pretty well. And so I don’t think we should think that we missed the chance to have a vaccine in hand that would work perfectly against SARS-CoV-2.

Q: I was just wondering if you can basically update the vaccine against novel coronavirus the same way the researchers or pharmaceutical companies upgrade the vaccine against the different strains of seasonal flu.

SARAH FORTUNE: Yeah. You know, so, it’s an appealing idea. There’s a little bit about the biology of the virus that’s a little different that makes me think that while you probably could get an immune response that would translate, the safety signals might be different and that it’s not quite as easy as swapping out the antigens in a way that we do with a flu vaccine.

Q: OK. Thanks a lot.

MODERATOR: Next question.

Q: Thank you very much. So something, a kind of debate that that pops up from time to time is on the mutation of the virus in one direction. You know, more virulent after that Los Alamos study, now in Italy in the other direction that it may be weakening to the point where you may be able to change policy. On the other hand, you have obvious compounding factors like a less acute outbreak will make you see people with less symptoms. It may appear to be other, you know, something maybe caused by something other than the virus, just what to get the usual time frame might be to to see those kind of mutations and the type of evidence you’d like to see to to be able to sort of confirm that that’s actually the cause of any changing trend.

SARAH FORTUNE: OK. I’m not a viral evolutionary biologist, and I guess while I read those papers with interest and it’s clear that there are different evolutionary trajectories for the different clades of this virus, I am wary of interpreting any one of those as evidence that we should be able to change policy because of exactly what you just said about the confounding effects. And so, what you sample and what you see, or what you see is highly impacted by what you sample, which can be conflated by all sorts of issues. And then what the trajectory of evolution is is also highly dependent on sort of both selective forces and bottlenecking in that population. And so I feel like they have the potential to be confounded by highly regional effects and make me wary of over interpreting them.

Q: Great. Thank you very much.

MODERATOR: Next question.

Q: Thank you so much. Have a general question about the different vaccine approaches that are being explored. So of course, some of the most advanced vaccines are using, you know, DNA, these DNA and RNA based vaccines but the technology behind these, of course, is unproven. You know, we don’t have a licensed RNA or DNA vaccine yet. So I just want to kind of get your general take on, you know, how likely is it that one of these genetic vaccines is going to be, you know, the vaccine that we have in a year. Or do you think it’s more likely that we’ll have a vaccine that relies on a more established technology?

SARAH FORTUNE: Good question. So, you know, the most established way of generating a vaccine is to take a pathogen and kill it, right? Either kill it just heat kill it or take a pathogen and sort of attenuate it. And the Sinovac vaccine, that’s the Chinese vaccine paper, that’s exactly what they did. So if you want to established, that is exactly what they did. And then the ad vectored vaccine, the ad platforms are much more established and have been used in a variety of different infections in large scale population trials. As you may know, the nucleic acid vaccines are appealing because of scaling and downstream manufacturing issues.

But you’re absolutely right. There’s a lot that has to be shown. And there are – you’re going to give a vaccine to a whole lot of healthy people. And so there are important safety parameters that have to be taken into consideration that I don’t think we have a good sense for in the nucleic acid based vaccine. And so I would expect that we’re going to have multiple vaccines with different efficacy profiles and different safety envelopes. You know, and that different, honestly, that different populations might have access to different vaccines, depending on the weird political, the nationalization of vaccine development. And I expect that probably a nucleic acid vaccine might be a part of that whole portfolio and I don’t know how it’s going to stack up against the more traditional, more established vaccine platforms.

MODERATOR: Do you have a follow up?

Q: No, I think actually I do have a question about the manufacturing aspect, and that has been, you know, one thing that, you know, Moderna and pursuing the nucleic acid vaccines have, you know, said that these are much better able to be scaled up much more quickly because the, you know, the starting materials can be can be produced fairly quickly. But I mean, I guess there’s not really a track record of of these vaccines being produced in large quantities. And for, I guess, other manufacturing facilities that are producing different kinds of vaccines, I mean, how easily would, you know, another facility be able to kind of quickly switch over and produce this? I guess I’m just curious about, you know, those claim of, you know, how easy is this really able to be manufactured?

SARAH FORTUNE: Well, I think what they’re saying is it’s not a biologic. So if you make an ad vector vaccine or you cook COVID and make it a vaccine, that’s a biologic product where you actually have cells in culture that you’re having to expand and then grow that virus. And as a biologic, there’s a lot that can go wrong in the biologic process, namely contamination. Like if you just think about the scale with which you’d have to do some the biologic manufacturing processes, adhering to the standards, the manufacturing standards for contamination and purity. That’s a hard process. And you can think of those nucleic acid vaccines to almost more like chemicals. You synthesize them, you’re not growing them. And so there is an inherent layer of simplicity. But you’re absolutely right. In part, we say that because we haven’t tried to manufacture and deliver one of these things, you know, at the scale of a billion doses. So it is possible that in scaling of that, we will discover problems in either the supply or delivery chain supply, manufacturing or delivery chains that really have not been evident before.

Q: Yeah. Thank you. That was really helpful.

MODERATOR: Yeah, great. Next question.

Q: Thanks for doing this. Do you have a sense of how many people worldwide would have to be vaccinated, in the US or worldwide would have to be vaccinated to provide herd immunity, to provide enough protection?

SARAH FORTUNE: So actually, that comes back to this – the point where we started was whether this vaccine is going to just protect against disease or it’s gonna protect against transmission. And so a vaccine that protects against transmission, actually, we are not going to have to deliver as many doses as the vaccine that protects against disease. Basically a vaccine that protects against disease means if you want to be protected, you have to get the vaccine and anybody who doesn’t get the vaccine is still at risk. And so it’s only by mitigating transmission that we’re gonna be able to achieve a meaningful epidemiologic, like a profound improvement on need at the demonology of the epidemic. And because we don’t really know yet if these vaccines are going to protect against transmission or to the extent to which they’re going to protect against transmission, it’s hard to predict. Except to say that the data that’s emerging suggests that there is a differential and there’s greater protection against disease than against at least carriage in the nasopharynx,  which might be a proxy for transmission.

MODERATOR: Do you have a follow up?

Q: Sorry, what would one have to look at? Yes. Thanks. What would we have to look at or what what are the things that would tell us one way or the other in looking at this data?

SARAH FORTUNE: Well, it’s hard. Transmission is really hard to measure. So what people are looking at is whether in these animal studies where they infect the monkeys after vaccination, they’re looking at the lungs to see disease, like did that monkey get COVID pneumonia and how much virus set up shop in the lung. But they’re also looking at viral carriage in the nose and throat, which they’re taking as a proxy for transmissible virus. And the vaccines that have the most – well, both, actually, all three: the DNA vaccine, the Sinovac, the ad vector vaccine – they do better against disease, so better in the lungs than they do against viral carriage in the nose and throat. Recognizing that viral carriage in nose and throat is just sort of one step towards transmission and we don’t really 100 percent know that’s going to be the correlate effect on transmission that’s going to be most meaningful.

Q: And of course, we don’t know how long immunity will last either by infection or a vaccination. Right. I mean, none of it.

SARAH FORTUNE: That is exactly true. Now, I do think that you’re absolutely right. And so when people have looked at immunity to other coronaviruses in settings of other vaccines, you know, it’s not like life-long immunity, it’s a couple years. And so, in experimental settings. So, I think your point is well-taken that the durability of immunity is also important. And that is probably going to be a feature of the vaccine platform itself. So that some vaccines are going to generate more durable immunity than others, and probably all of those vaccines are not going to do as well as natural infection. That’s the sort of common paradigm in infectious diseases.

MODERATOR: Next question.

Q: Hi, thank you, Sarah. My question is about the furin cleavage site that this version of SARS has. And I wondered whether that has an impact on vaccine development in any way.

SARAH FORTUNE: I do not think so. So, you know, these vaccines are taking different approaches, like Dan Barouch’s vaccine. He has six vaccine constructs that have different bits of the virus in it and I do not think that there is a way that that site is actually changing the immunogenicity of the spike protein or the receptor binding protein. But if you really cared about that, I would have to look more precisely.

Q: Okay. And I had one other question. Yeah, I heard that people who were infected with the first SARS virus, many of them are still carrying antibodies 18 years later. Do we have any sense of whether those antibodies might be neutralizing?

SARAH FORTUNE:  That is a fantastic question. Okay. So you know what that is? That is a) evidence of how  primary infection is just an incredible immunogen. I have not – and what you’d asked is kind of are those antibodies still neutralizing against the original SARS-CoV-1. And I have not seen that done. I think the exhortation would be that it would look like their original antibody response, so probably in most people they have a degree of neutralisation. Some people not, some people are great. But what it really highlights is if you have a primary infection, wow, it’s just like your body has seen that in a different way than a vaccine. And it really, really has a profound immunologic memory of that infection.

Q: Thank you.

MODERATOR: Next question.

Q: Thank you very much, last one, I promise. So it’s it’s just the one slice of human safety data we have is that pretty skeletal release from Moderna. But I just wanted to hear what your reaction was. Obviously a really small number of patients in the high dose, which they’re not moving forward with. You know, three transient great three flu-like symptoms. Is that in the realm, even given the sample size of what we might expect to see going forward. Or is that any reason for concern?

SARAH FORTUNE: OK. So when they talk about safety in this teeny phase one study, right, basically, they’re talking about really profound tolerability issues. So in the phase one study, they’re looking for tolerability, but they’re also doing dose finding, right. And so it is not uncommon to have tolerability issues at higher level doses. That happens all the time in both vaccines and drugs. And then you use that as a way to march your dose back. So that’s sort of acute tolerability. That is not quite the same thing as the safety issues that get most vaccines into trouble.

Most vaccines that have gotten into trouble, they find a dose that’s tolerable, right, and then they give it in the population, but in the population level, you know, we’re all different. And some of us very –  well, we’re all different, as you know, because most people get COVID and they’re fine and some people get sick. So at a population level, what we need to do is make the most of those who are gonna be fine, make sure they don’t then get sick. And the people who are going to get sick, either protect them or make sure we don’t make them sicker, right. And it’s that level of untoward interaction between the individual’s immunity and what happens, a challenge that gets a lot of vaccines into trouble. And the Moderna trial did not come anywhere close to addressing that more complicated safety question. Really, it was just like, did we poison you or not?

Q: A perfect – thank you. That’s a good way of putting it. I appreciate it.


MODERATOR: Next question, I think this might be our last one.

Q: Yeah. Thank you for give me the chance to ask another question. I don’t know if you mention also the progress made by the company Novavax. Nope. Anyway, I talked to a Novavax advisor and basically they said that their company developed some years ago in the wake of the SARS outbreak a vaccine or antibody, which actually targets the common pox, the common portion to better coronaviruses. So, basically their vaccine can target, and detect, and deactivate. Is it this possible? Or it’s plausible?

SARAH FORTUNE: It is possible. Honestly, I’d have to look at the Novavax vaccine data a little more carefully. I don’t have it at the top my head sense the validity of that. You know, you asked about flu earlier and what Novavax is talking about in that has been the holy grail of flu. Like, can you target something common to every flu strain so that you don’t have to get a new flu vaccine every year when it changes up its service parts., Right. And biologically, that’s really hard because the bits of the virus that it uses to invade are often the ones that are most impressive in terms of the kinds of protective immunity if you target them. And if you target some little bit of the virus that it doesn’t really care about but is shared across all viruses, you get an immune response but it didn’t do much. And so that’s called a universal flu vaccine. I know a lot about it in flu and I don’t know enough about it in coronavirus to know whether that’s plausible or not. But it is a biologically a holy grail, but it’s been a biologically really hard problem.

Q: OK. Thanks again.

MODERATOR: It looks like that’s our last question for today. Doctor do you have any final words before we go?

SARAH FORTUNE: No, thanks. It’s been a pleasure.

This concludes the May 21 press conference.

Howard Koh, Harvey V. Fineberg Professor of the Practice of Public Health Leadership (May 20, 2020)

Joseph Allen, assistant professor of exposure assessment science (May 19, 2020)

Michael Mina, assistant professor of epidemiology (May 18, 2020)