Akiko Iwasaki

Supercharging Antibodies for a COVID Vaccine

Air Date: September 28, 2020

Yale University immunologist Akiko Iwasaki discusses the science of antibodies and creating an efficacious COVID vaccine.


HEFFNER: I’m Alexander Heffner, your host on The Open Mind. I’m delighted to welcome Akiko Iwasaki to our broadcast today. She is a professor of immunology at Yale University. Welcome Professor.


IWASAKI: Thank you for having me, Alex.


HEFFNER: Professor, you wrote one of the most uplifting op-eds in recent memory in the New York Times since the pandemic, and I want you to summarize your basic thesis about antibodies, even if they don’t survive in us for more than three months or six months, your thesis is basically that we can still create a vaccine with great efficacy.


IWASAKI: That’s correct. So, many people confuse the immune response generated by natural infection to that generated by the vaccines. And the whole thesis of that op-ed was to distinguish that they’re not necessarily the same thing and that vaccines have a capacity to create a much more robust and long lasting immune response to a particular pathogen.


HEFFNER: And what you were saying, importantly, is that science can create a more robust response in the way that we ingeniously devise it, than nature. How is that possible that the virus can leave antibodies for only three months or six months in our bodies, but that we scientifically can create something that’s more resilient? Could it be for our entire lives or even with booster shots would it only provide a year or two years of immunity?


IWASAKA: Right. So vaccines are really empirical science that, you know, we don’t really know until we try it in humans, but from decades of experience from vaccine research, we know that some vaccines can induce very potent and long lasting immunity, much better than a natural infection with the same virus can. And the reason vaccines can do this it’s because, you know, science can basically design vaccines to target the immune response to the right area of the virus, for instance, the surface protein that is responsible for attaching to ourselves. And also we can add an event, which is sort of what stimulates the innate immune response to trigger a very potent antibody response against that vaccine antigen. So science has come a long way. So now that we can start designing and dosing the right kind of antigen and antibody combination to achieve a long lasting immunity.


HEFFNER: Is that combination what you found in a polio vaccine or other vaccines that were years, if not decades in the making, how does the pursuit of this vaccine differ from earlier research operations to create vaccines?


IWASAKI: Right. So historically people have used, you know, attenuated virus or killed virus as a vaccine, and that does not require any knowledge of, you know, molecular biology, as long as you can grow these viruses in culture and inactivate them or attenuate them. And that’s been sort of you know, old-school vaccines that people have used for decades. And they work very well, and they’re very safe as well, but the modern vaccines, the ones that are being currently tried are very, very sophisticated including the mRNA vaccine that basically takes the genetic material of the virus and introduces it into the host cells so that we can generate immune response against those antigens and also DNA vaccines and recombinant vaccines, which really focuses the immune response to a particular region of the, the virus.


HEFFNER: These are living vaccines versus the inactive ones that you described in polio?


IWASAKI: No. So the living vaccines are the ones that have been classically used, like the MMR vaccines they’re there they’re all live attenuated, you know living vaccine, whereas killed vaccines are polio vaccine comes in both forms killed and live attenuated, and they both work well. But the ones that I’m talking about it’s really sort of the very newest of vaccine, which is the nucleic acid based vaccines like RNA or DNA or recombinant vaccine, which only takes one protein out of the whole virus and sort of makes that one protein the antigen.


HEFFNER: Can those new ones on at scale be as effective as the old ones, we don’t really know yet, right?


IWASAKI: That’s correct. So all of these new, they were versions of the vaccines, we have much less experience with, for instance, the mRNA vaccine, if it were to be approved would be the first time that a vaccine that’s made of mRNA will be approved as a vaccine. So this is really cutting edge frontier, and we don’t have a lot of experience to rely on.


HEFFNER: But, you’re basically saying that you think that this path of the more modern renditions of vaccines, it’s the only avenue or versus the sort of older school approach, one strand of protein with what we’ve experienced for a novel corona virus and pathogen, it seems remarkable that that could have the efficacy of the older school rendition of vaccines. But you’re saying it can, potentially.


IWASAKI: That’s correct. I am not dismissing the old school vaccines at all. In fact, you know, they are also being tried in multiple different countries. So right now I’m not really bidding on any horses. I want all of these vaccines.


HEFFNER: Yeah. When you delineate between the approaches that we have Oxford and the drug companies that are involved, Johnson and Johnson, Pfizer, can you tell us what you think the two or three most promising ones are, and how scientifically they might be able to generate the antibodies that would provide herd immunity ultimately to the population?


IWASAKI: Right. So like I said, I’m not going to pick any favorites at this point, but what I am seeing is pretty promising results from both nonhuman primate, as well as human vaccine phase one and phase two results from all of the vaccine companies that you’ve mentioned. And so whether a vaccine can provide a robust and long-term immunity, that can only come in you know, phase three trials and we still don’t have any data from that yet.


HEFFNER: What is your assessment of the challenge vaccination proposals, so the idea of deliberately infecting people, do you have a particular take on whether that’s either scientifically smart or ethical to do?


IWASAKI: Human challenge experiment using SARS-Co-V-2, I think would be unethical because we just don’t know what the long-term consequences of this disease is, even in people who recover from so-called milder disease. And so I’m not in favor of human challenge experiments.


HEFFNER: Right. And that’s being discussed at Oxford and some other sites of early investigative work around vaccination. You don’t think, you think maybe that would be more disadvantageous even though theoretically it would expedite the scientific evaluation processes.


IWASAKI: Right. What we’re learning about this virus and its pathogenesis is you know, quite surprising, like every day we learn of new kinds of symptoms or disease or organ involvement. And I wouldn’t want even the healthiest of humans to become a subject of a challenge experiment.


HEFFNER: Does it also make it more difficult as a scientific experiment because we still don’t really understand the precise nature of asymptomatic or pre-symptomatic transmission?


IWASAKI: Right. And that’s why vaccines become absolutely critical because of this long period where people are either asymptomatic or pre-symptomatic from the virus and not being aware of whether you’re infected and infecting others. Really the only way to tell is whether doing like a daily, you know, testing or having a vaccine that would prevent that transmission altogether,


HEFFNER: From your perspective is there anything in the immunology that can say with some certainty or confidence, ultimately, that we understand more specifically the incubation period, or more specifically the nature of asymptomatic or pre-symptomatic transmission?


IWASAKI: Yeah. Well, that’s what we’re trying to do right now. The type of experiments that are required to understand the incubation period in pre-symptomatic period is a little bit challenging because you would kind of have to follow on infected persons you know, prospectively to see whether they get exposed and they become infected and how the viral titers change during the first few days of infection. And those data are really hard to come by. But we are trying to capture those events.


HEFFNER: And our program is only half hour. So our viewers don’t mistake us we don’t want to take any more time than we absolutely have to. With respect to genetic, our genetic composition and how we each country, each DNA sample roaming this earth has responded respectively for those who’ve been infected. How much are you interested in the diversity of genetic responses to infected cells? How much of that is your study?


IWASAKI: Right. So I think that genetics play a major role in how each individual responds to the virus. And we are really at the tip of the iceberg in terms of digging into the genetic sort of components. But there have been studies that are already coming out of different countries. There was a study from Netherland that showed that for young men who had severe, COVID had mutations in one of the key innate sensor genes known as Toll-Like receptor 7. And so it’s already revealing that, you know, genetics plays a major role in how we fight against this virus and how we respond.


HEFFNER: Do we know anything yet, Professor about the genetic composition that is perhaps strongest, most formidable in responding to the spike protein, that novel nature of this virus compared to other viruses?


IWASAKI: Right. That would require a lot bigger study. Right now the genetics that are coming out are people who have very severe diseases. And those are easier to spot than who are very robust because we’re not catching those people who are absolutely resilient cause they’re not coming to the hospital. So we always start from the most vulnerable to the most robust. And we’re not there yet.


HEFFNER: Did you think kind of from a bird’s eye view of someone who studies this that the next pandemic would be and the next novel virus would be the spike protein type of Corona virus? I mean, do you think you and your colleagues were anticipating that the next big endeavor scientifically would be having to create a vaccine or therapeutic to respond to a kind of coronavirus specifically?


IWASAKA: I wouldn’t think so. It wasn’t like the most top predicted virus to become pandemic. People were much more paying attention to avian flu or some other kinds of pandemic flu. But you know, as you say, it’s actually really not easy to predict where the next pandemic is going to come from.

HEFFNER: Your op-ed suggests, but correct me if I’m wrong is that you could potentially create a vaccine that would address future coronavirus epidemics, or pandemics based on how similar the pathogen might be to what we’re experiencing now, is that right?

IWASAKI: Right. I think it is possible to design a more universal type of vaccine that would block spike protein that is, you know, commonly shared against different types of coronavirus or different types of influenza virus. And there’s a huge push towards making a universal vaccine to influenza virus. So in the future, I think it is possible. We’re not there yet though.


HEFFNER: What are the major hurdles? And, the size the novelty is it, does it always come back to the spike protein and how we respond to it? I would like you to give us an education on the T cells and the realities of COVID-19 that are not the realities of influenza,


IWASAKI: Right? So every virus has its Achilles heel, which is different and the spike protein, because it’s the one that the virus uses to attach to our host cells, without that it’s not infectious. And so spike protein is the target of vast majority of vaccines and monoclonal antibody endeavors. But you know, there are more than just antibodies. Immunity consists of multiple different cell types, including antibody secreting B cells, but they’re also T cells and T cells also respond to viruses in a unique way that it can distinguish influenza versus coronavirus based on the amino acid sequence of the viral protein. So T cell based vaccines are also being considered, it’s again, not at the cutting edge front yet, but I think having T-cell inducing ability, as well as antibody inducing ability will be a sort of a complete package with respect to a robust vaccine against this virus.


HEFFNER: Now you’re involved in the laboratory, right?


IWASAKI: That’s correct.


HEFFNER: So can you take us inside a day of what it’s like to study our pandemic emergency response?


IWASAKI: So, I’m an immunologist, so we study the immune response to the virus. And so what we do is we enroll patients who are coming into the hospital we collect various bio-specimens from the patients to be able to analyze what’s going on in terms of immune response against this virus. So we will, for example, collect blood cells from the patients and in real time analyze what compositions of blood cell types there are, as well as what kinds of cytokines they’re secreting. And that has allowed us to kind of predict signatures of immune response that are associated with recovery versus worse disease. And so, yeah, daily, we are collecting blood, analyzing them and trying to understand immune response.


HEFFNER: And, and this has to really be a tag team with virologists, right? So the immunologists on one side and the virologists on the other side, how does that work as a unit?


IWASAKI: Oh, it works very well, especially where I work. At Yale we have really integrated team, so not only virologists and immunologists, but also the clinicians and the nurses and the staff that are, you know, collecting and enrolling patients, collecting samples. There are transporters that run the sample across the campus to the laboratories. We also have virology colleagues that are sequencing the viral genome to be able to tell whether it is something unique about the virus is causing people sick. So as you say, it requires a village to really try to understand this pandemic. And we have one here.


HEFFNER: Despite the early warnings of mutations that really hasn’t been manifested so much in terms of your study or virologists’ study of COVID-19, right?


IWASAKI: So, like any other RNA viruses, Coronaviruses do acquire, you know, variants, but it doesn’t appear to be that there is a variant that have escaped the immune response or that are much more virulent than others. So those haven’t been seen so far.


HEFFNER: On the college campus, how do you expect this fall to operate in terms of how effective medical schools that have this important investigative function with the new realities of teaching digitally do you think that will help or hamper the ongoing investigation for a vaccine?


IWASAKI: Right. So it’s a very unique time and none of us are used to this, but I think it’s also an opportunity. It’s an opportunity to learn and opportunity to teach. And so I teach medical students here at Yale and what an opportunity to be in the medical school, during a pandemic period and I think we have to take advantage of what we, what we have here.


HEFFNER: And the next generation may well help you in resolving this crisis and providing health and medical security for generations to come.


IWASAKI: I hope so.


HEFFNER: So that’s, that’s the hope, but from your perspective, as someone who’s responding to immune reactions to the virus, you have to, you likely think about colleges reopening with some trepidation, just in terms of the spread and the contagiousness of this and some of those novel aspects of this that make it, what it’s been dubbed, the invisible enemy. So, you know, for those who are viewing that, or either studying remotely or who have reengaged in some kind of socialized educational experience now, what would be your suggestions in how we monitor patients or potential patients and immune responses within these largely student communities, but student and faculty communities that are so concentrated and sometimes densely populated,


IWASAKI: Right? Yeah. I do share your worry about a potential transmission. I, especially because students are coming from many areas of the country in which the COVID is still on the rise, whereas in Connecticut, we have sort of been able to control the first wave. And so I think monitoring, you know, monitoring and really quarantine people who are found to be positive and having that infrastructure would be key to contain the spread, but the potential spread of the virus on the campus.


HEFFNER: From the immunologist perspective, you know, we’ve reached a point with COVID where it’s necessary, that will, will require a vaccine or a therapeutic that is effective, but, you know, it depends on how well you mitigate it. And for instance, with SARS, the original SARS there was a contained response to the point that a vaccine was not imminently necessary, but when you think of the requisite steps now to target the protein and the sort of viral sample that will be integral to the vaccine, what is the timetable that you think is realistic? And is there a point of containment even with millions around the world infected and some dead and some with lifelong medical complications and injury, is there a point of containment where the way you approach the vaccine would change versus a wildfire of virus spreading all around the world?

IWASAKI: Right. So I don’t think vaccine should be the only kind of way forward. We have to practice physical distancing measures, wearing masks, washing hands, all of these public health measures at the same time, even when the vaccines come on, because we’re not going to have billions of doses of vaccine on day one – it’s going to take a while to distribute the vaccine and to develop immunity in the persons who are immunized it may likely require a booster shot, you know, and so a few months of immune response has to be developed before you’re really protected. So you know, it’s not an instantaneous shot in the arm and you’re good. So I want people to remember that all of these other, you know epidemiological practices absolutely important until we reach a point where everybody’s vaccinated.


HEFFNER: Given the maladministration of the government here, and in many other countries that fail to respond adequately. I mean, you’re going to do the science, but it’s hard because you can’t ensure that it’s not manipulated and that you know, scientific processes are heated. Do you have confidence that despite some of the anti-science governments that exist now that the drug companies and universities like your own will ensure that whatever the first vaccine is on the market and subsequent boosters are scientifically sound?


IWASAKI: Absolutely. So I think the scientists are coming together too in solidarity to support that kind of research. And so that’s why we speak out when there is misinformation or panic. And that’s part of the reason I wrote the op-ed with Ruslan Medzhitov. It is really, we have a role to play in the society with respect to educating the society, as well as kind of you know, demystifying some of these information and rest assured that the vaccine companies are doing their best to ensure safety and efficacy because even in the pendant, especially during the pandemic, this becomes really important that the right kind of scientific studies are done before the distribution of the vaccine occurs.


HEFFNER: Right. I mean, if you think of just this, the threats, not to public health, but to information literacy, you know, if you release a vaccine prematurely and you see horror stories of death, and the percent is not exaggerated, but the anecdotes that emerge immediately are negative ones, then that will shade a whole year’s worth, if not longer of public opinion on this. So, you know, you have the threat of a vaccine that you think works, but then it doesn’t work as well as it’s projected to, or, you know, you have, you have a kind of mis-statement misrepresentation of what’s happening. I mean those must be central to your thought process right now.


IWASAKI: Absolutely. And it’s really important to fight back when there is misinformation. And I think we’re doing our best, but the public has to buy in to the importance of science. Otherwise we cannot really communicate the importance of that.


HEFFNER: Scientifically, have we ever been in the same space where like, we’re unsure of the efficacy, potential efficacy of the vaccine and then we have to ethically make a decision about when to pull the plug if the first vaccine ultimately is, is harmful and not helpful to people’s health?


IWASAKI: Absolutely. So that’s why the phase three results are really important because then thousands of people are going to be tested against a particular vaccine, if there’s any unusual or harmful effect from the vaccine, the vaccine company will be the first to pull that vaccine out of the market, because that will be detrimental.


HEFFNER: But you have confidence in both the scientific rigor and ethics that are being implemented in those companies, that we should feel confident that they are going to go by the scientific method?


IWASAKI: I do have confidence in that.


HEFFNER: And finally, just the last question very quickly is what percent do you think would, would mean that you’d have to pull the plug on a virus? What percent of patients or vaccine recipients who have inimical health results, like is that 15 percent? Is that 7 percent? I mean have we even been here before as a society to determine what that percent should be?


IWASAKI: Yeah. The percent is likely going to be low because the, you know, we are giving vaccine to healthy people. And if we’re seeing, you know, even like 1 percent of the population vaccinated, having such a harmful effect, I am sure that that’s going to trigger a red flag on the side of the regulator, as well as the vaccine company.


HEFFNER: And, in the seconds we have left, what will be the best way to know that it’s working?


IWASAKI: Oh, the best way to know it’s really to see how well the vaccinated people are protected from, you know, infection or disease from this virus. And that will be compared to people who are vaccinated with placebo vaccine or non-vaccinated.


HEFFNER: Professor. Thank you so much for your insight. And, and most of all, thank you for the extraordinary task you’re undertaking with your colleagues at Yale and around the world.


IWASAKI: Thank you very much, Alex. My pleasure.

HEFFNER: Thank you. Please visit The Open Mind website at Thirteen.org/OpenMind to view this program online or to access over 1,500 other interviews and do check us out on Twitter and Facebook @OpenMindTV for updates on future programming.