What Will The Next Generation Of COVID-19 Vaccines Look Like?

IRA FLATOW: This is Science Friday. I’m Ira Flatow. It’s been a little over 2 years since the first COVID vaccine was approved, and since then, we’ve seen the virus continue to mutate, and with each new variant, the virus seems to evade our current vaccines more effectively, faster than we can make effective new mRNA boosters.

What’s more, coronaviruses frequently spill over from animals to humans. Think the original SARS and MERS viruses. Both are coronaviruses. So how can we make vaccines to better protect us against the emerging variants, and even prevent future pandemics?

Researchers are working on the next generation of coronavirus vaccines that do not depend solely on the mutating spike proteins. Joining me now to talk about her work on a new type of vaccine, which offers protection against COVID-19, as well as a large group of other coronaviruses, is Dr. Pamela Bjorkman Professor of Biology and Bioengineering at Caltech based in Pasadena, California. Welcome to Science Friday.

PAMELA BJORKMAN: Thank you for having me.

IRA FLATOW: Nice to have you. So let’s start off. Can you explain how your vaccine works? I understand you create a nanoparticle from eight different types of coronaviruses.

PAMELA BJORKMAN: That’s right. First, let me just say that the theory behind this is that if we could make a vaccine that would direct our immune system to recognize the conserved parts of various coronaviruses, then we would, in theory, be protected against whatever might spill over in the future or whatever variant of the current SARS-CoV-2 virus that’s causing the COVID-19 pandemic right now.

IRA FLATOW: So you’re basically creating a vaccine that attacks the parts of the virus that don’t mutate, that don’t change very much.

PAMELA BJORKMAN: That’s right. There’s parts that tend to stay the same. And we studied this for quite a while structurally, looking at the three-dimensional structures of these spikes. When we inject this into animals, in our animal test experiments, we actually do raise these conserved antibodies. But if we inject the homotypic nanoparticles, we raise what’s usually raised by the current vaccines, which is the more variable antibodies.

IRA FLATOW: So how effective does your work show that any new variant that shows up, people would be protected using your new vaccine?

PAMELA BJORKMAN: Yeah, that’s a great question. I mean, we’d have to actually do all of those protection experiments in people to prove that. So we’ll be doing a clinical trial that’s funded by CEPI, the Coalition for Epidemic Preparedness Initiative, but that hasn’t happened yet.

But what we can do is we can extrapolate, because when we started this work, there were no SARS-CoV-2 variants. I mean, we started at the beginning of the pandemic. We didn’t know about alpha, or beta, or any delta, or any of the omicrons. But as those arose, we started using those in laboratory evaluations, and we’re observing neutralizing activity against the variants that didn’t even exist when we started.

IRA FLATOW: When do you think you could do the studies in humans?

PAMELA BJORKMAN: Well, it’s scheduled for some time in 2024. There’s a lot of regulatory things and manufacturing things. It’s a complicated vaccine to make.

And I did want to be careful about– we have observed neutralization of SAR-VCO viruses, meaning SARS-like betacoronaviruses, but the conservation between viruses doesn’t extend to, say, common cold viruses or to MERS, which is a different type of betacoronavirus. So this is not a universal coronavirus vaccine, by any means. I’m not sure it would even be possible to make one of those, although people are trying.

IRA FLATOW: We’ve reported on the show the monoclonal antibodies we’ve relied on this far in the pandemic to treat people with severe infections are no longer effective on current variants. I understand that your research could also lead to better treatments. Is that correct?

PAMELA BJORKMAN: Well, the great thing is, when we inject the mosaic eight nanoparticles into mice, we can make monoclonal antibodies that target conserved regions, and that would work against new variants because as long as you target that conserved region, it’s not going to matter, for the most part, the variations that occur in these places that are separated from the conserved region, and the monoclonal antibody therapeutics were targeting the more variable regions.

IRA FLATOW: Will you be making them?

PAMELA BJORKMAN: Well, we’re certainly going to make them in the laboratory. I run an academic lab. We don’t manufacture products for use in people, but I’d be very happy for this technology to be used.

IRA FLATOW: Well, maybe when people hear about this.

PAMELA BJORKMAN: Yeah, maybe.

IRA FLATOW: Some company’s listening.

PAMELA BJORKMAN: Maybe.

IRA FLATOW: Might get some interest. Speaking of things that aren’t working as well anymore, we’ve now had several rounds of mRNA COVID-19 boosters, and I’m talking about those from Pfizer and Moderna. What are the drawbacks of that approach versus looking into other kinds of vaccines like the ones you’re working on?

PAMELA BJORKMAN: The problem here, again, is, even though the mRNA technology is so fast, you can’t possibly keep up with the variants these days. You could do that. You can keep changing it, but you’re just fighting a losing battle. But we think our approach would just not need updating.

IRA FLATOW: And that’s what your competitive advantage is, is that your vaccine, your technology is not just chasing new variants, but you’re there for anything new that comes up.

PAMELA BJORKMAN: Yeah, I think so. Our evidence is we tested it against very distant SARS-CoV-2 viruses that are found in bat caves in Russia, for example. So really distant from SARS-CoV-2. These have not spilled over into humans, but they could.

And in fact, these SAR-VCO viruses spill over into humans all the time. So people who live near bat caves, if you look at their blood, you find they make antibodies against these bat viruses because they’ve been exposed. But, fortunately, they don’t transmit the viruses, or even get sick.

And then, every once in a while, unfortunately, a virus transmits that’s able to then infect someone else, and then, if it’s a transmissible enough virus, we end up with a pandemic. And so we have no idea when the next one is going to happen. And so we’d like to provide protection ahead of time to prevent another pandemic.

IRA FLATOW: And you think this would do it?

PAMELA BJORKMAN: We hope so. We definitely hope so, yes.

IRA FLATOW: Well, Dr. Bjorkman, thank you for taking time to be with us today. Fascinating research. Thanks for describing it.

PAMELA BJORKMAN: Well, thank you. It was a pleasure.

IRA FLATOW: Dr. Pamela Bjorkman, Professor of Biology and Bioengineering at Caltech in Pasadena. And now, I want to talk about another promising next generation COVID vaccine, nasal vaccines. The hope is that this type of vaccine will offer broader protection, used in conjunction with the currently available mRNA vaccines. But nasal vaccines have faced major roadblocks in getting approval, unlike the original shots from Pfizer and Moderna, which benefited from funding and support from Operation Warp Speed, which no longer exists.

Joining me now to talk more about her work on a nasal vaccine is my guest, Akiko Iwasaki, Professor of Immunobiology and Molecular, Cellular, and Developmental Biology at Yale University based in New Haven, Connecticut. She’s also a co-founder of Xanadu Bio, which has licensed her nasal vaccine technology. Welcome to Science Friday.

AKIKO IWASAKI: Thank you so much for having me.

IRA FLATOW: Nice to have you. OK, let’s start off by explaining to me how the nasal vaccine you’ve developed works in conjunction with the mRNA vaccines many of us have already received.

AKIKO IWASAKI: So the vaccine strategy that we developed is called prime and spike, and it leverages the immune responses that are already developed by the mRNA vaccines and directs that immune response to the nasal cavity by using a nasal spray booster that works in conjunction with the current vaccines. So now that we have all received multiple doses of vaccines, or have been infected prior with SARS-CoV-2 virus, we now have existing immune responses that are circulating throughout the body, but very little is actually maintained within the nasal cavity and the throat where the virus actually enters our own body. So what we want to do is to convert that systemic immune response by using a nasal vaccine to prime a mucosal immunity in the nose.

IRA FLATOW: So you want to attack it, basically, as it enters the body in the nose?

AKIKO IWASAKI: Exactly. We want to have the shield placed right where the virus actually attacks us.

IRA FLATOW: And we’ve been discussing new variants of COVID-19, how they’ve been cropping up faster than scientists can develop mRNA boosters to attack them. Would your approach solve this problem?

AKIKO IWASAKI: Yeah. So we think that our approach of nasal booster will solve part of that problem because the nasal immunity relies on a different kinds of antibody called IgA, and IgA, unlike the IgG, which is circulating throughout the body that’s induced by conventional vaccines, IgA has four arms to attach to the virus surface, whereas the conventional antibodies are two arms. And we think that having the four arms to attach to a virus means that there is more ability of that cross-reactive response provided by IgA, and we’re hoping that would cover some of the mutating variants of concern.

IRA FLATOW: Well, so what you’re saying, if I understand you correctly, is that while the vaccines we have now prevent us from getting severe diseases, from going to the hospital, possibly, your nasal vaccine would prevent the initial infection. Is that correct?

AKIKO IWASAKI: Yeah, that is what we want to achieve, if we can prevent all the infection, at least reduce the amount of infection. And also, that means that we can reduce the amount of transmission that a person can have if you’re vaccinated in this way.

IRA FLATOW: And you published your research in Science last year showing your vaccine is effective in reducing transmission of the virus in hamsters, but you have faced some pretty major roadblocks, have you not, in moving forward with the next stage of research. Please, tell me about that.

AKIKO IWASAKI: Right. So the pre-clinical animal studies look really promising, and we’re very happy to proceed with that. But as you said, because we don’t have a Warp Speed type of effort anymore, we are just sort of back to the normal speed of vaccine development, which normally takes years. So some of the roadblocks include the fact that we don’t have funding to be able to start a phase I clinical trial, as well as not having access to the mRNA vaccines that are currently thrown out when they’re not used. We don’t have access to that kind of mRNA vaccine in order to even do further studies in the animal models.

IRA FLATOW: Wait a minute, you can’t get the mRNA vaccine that they’re throwing out, that Pfizer and Moderna may be chucking out?

AKIKO IWASAKI: That’s correct. So the providers of vaccines have signed a contract with the government saying that they will not be using the remaining vaccines for any other use, and that was put in place, I believe, in the very beginning of the pandemic in order to prevent misuse of the vaccine. But that contract still exists, which means that we cannot use the wasted vaccine for our research purposes.

IRA FLATOW: So you had to pay a lab, you had to pay for it to create mimic vaccines, I understand.

AKIKO IWASAKI: That’s correct. There are companies that are making mimic vaccines that people like myself and other scientists are having to use in order to do more research in this mRNA vaccine field.

IRA FLATOW: So if you could do more research and move forward, how soon could you begin clinical testing in people?

AKIKO IWASAKI: Well if we are to somehow miraculously raise enough money to–

IRA FLATOW: How much money are we talking about raising?

AKIKO IWASAKI: I think we are talking about tens of millions of dollars, because that’s what it takes to develop a GMP quality material which is fit for use in human clinical trials. And of course, you have to pay a lot of other parties in order to develop a first phase clinical trial. So it’s not something that a research lab can easily do.

IRA FLATOW: So you need a partner.

AKIKO IWASAKI: Yes. Yes, absolutely.

IRA FLATOW: So you’re desperately seeking one.

AKIKO IWASAKI: Yes, desperately seeking partners who are able to help us launch a first phase clinical trial of our promising vaccine approach.

IRA FLATOW: This is Science Friday from WNYC Studios. If you’re just joining us, I’m talking with Yale immunobiologist Akiko Iwasaki about her work on developing a nasal COVID vaccine. Nasal vaccines, as you say, are newer. Are you still working out the best way to measure how effective they are?

AKIKO IWASAKI: Yeah, so that’s the other, not a hurdle, but something that we have to work out as a scientific community, is to be able to measure mucosal immunity in a standardized way. Because for the circulating antibody levels, there are standard ways of measuring antibody levels, and potentially, correlates of immunity, but for nasal vaccines or any mucosal vaccines, we don’t have a mucosal correlate of immunity yet. So what we need to do is first find out, what is the standard method? What is the best method to measure these antibodies? And what are the levels of antibodies needed to prevent infection and transmission?

IRA FLATOW: It seems like your vaccine would be especially important given now that we’re, again, seeing a new variant dominating. I’m just surprised to see why we aren’t seeing the type of investment, as you say, that we saw with Operation Warp Speed, which generated the original COVID vaccines.

AKIKO IWASAKI: Yes, I’m equally puzzled and frustrated for not being able to move faster with our vaccine strategy. We’re not even asking for Warp Speed. We’re asking for lightning speed to be able to bring this to human clinical trials as soon as possible.

IRA FLATOW: People are tired of talking about COVID, right? And it seems like the government has less appetite to push these things through. There’s money even stalled in Congress for moving forward with COVID issues.

AKIKO IWASAKI: Absolutely. So that’s the other issue that we’re dealing with, is that a part of the society has sort of decided that this is no longer a priority, but we are still in the pandemic. It’s not over yet. And we are also seeing some very concerning consequences of having even a mild infection with COVID turning into long COVID. And so that’s the other reason we want to promote a nasal vaccine that will prevent any diseases downstream.

IRA FLATOW: As I wrap up here, I want to broaden a bit, if you will. I mean, how can what you and other researchers are learning with these next generation vaccines be used for other viruses?

AKIKO IWASAKI: Yeah, that’s a great question. Our approach can be adapted to any other respiratory viruses, because all we’re doing is to leverage the existing immunity that’s developed by either immunization or infection and really strengthening the nasal mucosal immune responses. So we are currently expanding our approach to influenza virus and other respiratory viruses to be able to see if we can combine these kinds of approaches for other respiratory diseases.

IRA FLATOW: We have run out of time, Dr. Iwasaki. I want to thank you for taking time to be with us today. And good luck in finding the funding you need on this really interesting research.

AKIKO IWASAKI: Thank you so much, Ira.

IRA FLATOW: Dr. Akiko Iwasaki, Professor of Immunobiology and Molecular, Cellular, and Developmental Biology at Yale University, of course, based in New Haven, Connecticut.

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