2021 was the unofficial year of mRNA—and deservedly so. But the science behind the technology is not always easy to understand. In this episode, we will dive into the miracle technology that saved countless lives and talk about what it holds for the future. We also speak to a biotech company about its non-mRNA vaccine technology for COVID and why the healthcare ecosystem will always need multiple options.
2021 was the unofficial year of mRNA—and deservedly so. But the science behind the technology is not always easy to understand. In this episode, we will dive into the miracle technology that saved countless lives and talk about what it holds for the future. We also speak to a biotech company about its non-mRNA vaccine technology for COVID and why the healthcare ecosystem will always need multiple options.
Speaker 1 (00:08):
Today we have a question which asks, can the mRNA from the COVID vaccines, so the Pfizer and Moderna vaccines, can they incorporate into our DNA? So that's a good question.
Speaker 2 (00:20):
Chips this one could eventually be used to monitor, diagnose, or treat medical problems, but there's a twist. The Columbia team's work also collided with the world of online conspiracy theories, much to their dismay.
Speaker 3 (00:33):
You may have come across a viral news item of Nobel Laureate, Luc Montagnier in which it is purported that the scientist claimed that whosoever took the COVID-19 vaccine will die in two years. If you have not come across it, then you can mark yourself safe from fake news.
Speaker 4 (00:51):
Regarding the genetic COVID vaccines, the science is settled, they're not working.
Dr. Michelle McMurry-Heath (00:58):
As soon as mRNA vaccines for COVID-19 hit the market, misinformation began to infiltrate parts of the media. Social media influencers became scientist overnight. Everyone was an expert. Some people believed the hype and they became fearful of what they viewed as new and untested technology. To be fair, science isn't always easy to digest. Even for people who trust the science, many may find that they don't always completely understand how it works.
Dr. Michelle McMurry-Heath (01:32):
Today, we will dive into the miracle technology that saved countless lives and talk about what it holds for the future. We also talk with a company taking a more traditional approach to developing a vaccine for COVID-19 and discuss why several options can help get more people vaccinated. I'm Dr. Michelle McMurry-Heath, and you are listening to I am BIO.
Dr. Matthew Miller (01:57):
Some of the misinformation that's become rampant in the context of mRNA vaccines. There's the idea out there that they modify our DNA or that there's some sort of gene therapy, which is not accurate. Obviously these vaccines are transient, they don't alter our genomes. That perception is now out there, and it's much more difficult to alleviate those misconceptions once they've already been formed than it is to address them both before they become an issue.
Dr. Matthew Miller (02:47):
So some of that public perception will be a battle for this technology going forward but I think there's also the hope that the tremendously good safety that we've observed in the context of widespread global use of mRNA vaccines during the current pandemic will also provide reassurances that the technology is a safe technology going forward.
Dr. Michelle McMurry-Heath (03:09):
This is Dr. Matthew Miller.
Dr. Matthew Miller (03:11):
My name's Matthew Miller. I'm an associate professor in the department of biochemistry and biomedical sciences in the DeGroote Institute for Infectious Disease Research at McMaster University in Canada.
Dr. Michelle McMurry-Heath (03:24):
Dr. Miller is a viral immunologist and vaccinologist by training. Before the pandemic, he was studying vaccine platforms for infectious diseases like influenza.
Dr. Matthew Miller (03:34):
My group's been interested for a long time in understanding seasonal flu vaccines, and in thinking about ways to design better and broader flu vaccines that would be capable of providing protection across multiple seasons. Our interest in vaccine platforms that can be used to generate immunity is really what drew our attention to mRNA vaccines. And of course, influenza is one of the applications for which we've seen quite a bit of preclinical work, looking at their utility in the context of seasonal and pandemic influenza prior to COVID-19.
Dr. Michelle McMurry-Heath (04:22):
Dr. Miller described for us exactly how mRNA technology works and explains how it differs from traditional vaccines.
Dr. Matthew Miller (04:31):
Most traditional vaccines historically have used either killed pathogens or pieces of killed pathogens to generate immunity. And that process in itself presents some pretty formidable barriers in certain cases. For pathogens that have to be manipulated under high containment conditions like SARS-CoV-2 which can only be handled in biosafety level three laboratories which are highly specialized facilities, it's very difficult to grow large amounts of these pathogens then subject those pathogens to chemical or physical forces that kill them prior to purifying them and administering them as a vaccine.
Dr. Matthew Miller (05:27):
In addition, those older technologies that use inactivated pathogens or components of inactivated pathogens sometimes present challenges when it comes to boosting. Because if we have immunity, partial immunity to those pathogens already, what happens is that when we inject them, our immune system sort of immediately eliminates some of the vaccine such that it's not capable of restimulating our immune system.
Dr. Matthew Miller (06:02):
MRNA vaccines are different because we're not providing the component of the pathogen directly. What we're doing is we're providing our cells with a code that teach the cells themselves how to make that pathogens component. And one thing that's unique about mRNA based vaccines is that instead of delivering an antigen or a component of a pathogen directly in the vaccine, what mRNA vaccines do is they deliver the message for how to make a particular component of a pathogen into our own cells and then our cells make the antigen themselves.
Dr. Matthew Miller (06:45):
The reason that's important is because in addition to generating strong antibody responses, when our cells make antigen the way they would during a natural infection, they also are capable of stimulating other branches of the immune system more effectively, especially T-cells which are the other major important branch of the adaptive immune response that vaccines are designed to elicit in order to protect us from subsequent infection.
Dr. Michelle McMurry-Heath (07:16):
And although mRNA technology was discovered many years before the pandemic, scientists hadn't quite figured out how to deliver an mRNA vaccine into the body.
Dr. Matthew Miller (07:29):
There's been a lot of excitement in the vaccinology field about the potential of mRNA vaccines for some time. But historically, there had been a few major challenges that we needed to overcome before mRNA vaccines were really ready for wide scale use. One of the major issues is that mRNA as a biomolecule is very susceptible to degradation.
Dr. Matthew Miller (07:57):
And so we had to find ways to protect the mRNA so that when we vaccinate individuals, it finds its way into immune cells and can then generate immune responses. And that was really non-trivial. It required a lot of bioengineering expertise to change the structure of the mRNA itself to protect it, but also the design of the nanoparticles which are used to deliver mRNA was also a really important advance that has allowed these vaccines to get to market.
Dr. Michelle McMurry-Heath (08:30):
Once the delivery obstacle was discovered and overcome, the rest as they say is history. Billions of mRNA doses have now been administered around the world. When we combine all types of vaccines, the total is 11 billion, quite a remarkable achievement. But everything wasn't smooth sailing for the mRNA vaccine. Dr. Miller explained some of the challenges of getting these vaccines distributed.
Dr. Matthew Miller (08:59):
Cold chain requirements for the distribution of mRNA vaccines, this was a really pressing issue at the outset of the pandemic when these technologies were first being distributed because they needed ultra cold storage in order to maintain activity. Subsequent work has shown that those cold storage requirements are not as stringent as we initially thought.
Dr. Matthew Miller (09:23):
Nevertheless, they do require strict cold chain maintenance, and that can sometimes limit the accessibility of these vaccines in resource poor areas, low and middle income countries, et cetera, which are often the places that would really benefit most from these vaccines. There's a lot of work being done on technologies to thermally stabilize these vaccines so that they're more amenable to transport in situations where it's more difficult to maintain strict cold chain requirements.
Dr. Matthew Miller (10:04):
All of the mRNA vaccines are designed to generate immunity against spike. For certain pathogens, it's beneficial to generate broader immune responses against a multitude of the pathogens' proteins. This can, in some cases, create more effective immunity, but can also guard against declines in vaccine effectiveness that we see as pathogens mutate as we're currently observing in the case of variants of concern, for example. It is possible to make mRNA vaccines that contain multiple antigens but the scaling becomes increasingly difficult. And in certain cases, there may be other technologies for which doing that is more straightforward.
Dr. Michelle McMurry-Heath (10:52):
There is no question that mRNA vaccines changed the course of the pandemic and saved countless lives. And we are grateful to all of the scientists and researchers who made their delivery possible. But how can we take this breakthrough and adapt it to other diseases, many of which have stymied scientists for generations?
Dr. Michelle McMurry-Heath (11:15):
When we come back from a break, Dr. Miller talks to us about some exciting mRNA based treatments for diseases that have previously been difficult to address.
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Speaker 7 (12:22):
The implications for this messenger RNA go way beyond just the current COVID-19 pandemic. Experts say that messenger RNA technology could be used to combat both emerging and existing viruses and diseases.
Dr. Michelle McMurry-Heath (12:35):
We're back with Dr. Miller who describes what this science can accomplish.
Dr. Matthew Miller (12:40):
So I think there's a very exciting future. We've also learned a lot about the particular strengths of mRNA vaccine platforms. And so applying those strengths to other high priority pathogens is something that will be relatively straightforward because one of the major benefits of mRNA vaccines is that they're very amenable to being updated.
Dr. Matthew Miller (13:04):
Many people refer to them as a plug and play platform, meaning that you can sort of plug and play antigens from whatever pathogen you're interested in into that system in a relatively straightforward way that doesn't require fundamental changes to the technology or the way those vaccines are produced.
Dr. Michelle McMurry-Heath (13:26):
But it's not only infectious diseases that can benefit from this technology. Research is now being done on what we call that therapeutic cancer vaccines, which are fundamentally different from vaccines that protect us from a future infection as Dr. Miller explains.
Dr. Matthew Miller (13:44):
The way that many of these vaccines are being used is in a therapeutic setting. And the way this works and the reason it works is because in many types of cancers, our bodies express mutated proteins which are called cancer associated antigens. They're essentially mutated proteins that are unique to cancer cells and not typically found on other healthy cells and tissues in our body. And our immune system is capable of recognizing those cancer or tumor associated antigens.
Dr. Matthew Miller (14:19):
If our immune system can recognize those effectively, it can selectively kill tumors and thereby protect us from cancer and help to eliminate preexisting cancer as well. Some of the early clinical trials and the preclinical work looking at mRNA vaccines for that application, I think have been really promising too and it's a really novel approach. But I think there's a lot of excitement around looking forward to mRNA vaccines that may have clinical utility in treating and maybe even preventing cancer going forward.
Dr. Michelle McMurry-Heath (14:56):
The bar is a bit higher when it comes to cancer because cancer cells develop from within, they don't enter our bodies from the outside like pathogens that cause infectious diseases.
Dr. Matthew Miller (15:08):
As a general principle, it's easier for our immune systems to make responses against things that are what we call foreign immunologically, meaning things that don't naturally occur in our bodies. So components of viruses or bacteria or fungi, or parasites are things that are not supposed to be parts of our body. And so using vaccines, it's more straightforward to be able to train our immune system to recognize those things.
Dr. Matthew Miller (15:39):
Because as we develop, our immune system learns not to attack our own cells. When it does, obviously it leads to significant problems like auto immunity. So we've evolved in such a way that our immune system learns to ignore what we call self antigens or components that are found in our own bodies. In the context of cancer, what we often see with tumor associated antigens is either the expression of proteins, which sometimes arise during development, but aren't normally expressed as we are neonates and then into adulthood.
Dr. Matthew Miller (16:21):
And so we can, with some work, teach our immune system to see those things as foreign. And ditto for proteins that sometimes become mutated as a result of the genetic instability of cancer cells, they still have qualities that make them look like a self antigen, but there are sufficient differences that we can train the immune system to see them as foreign. It's just the bar is higher to do that because our immune system tries so hard to protect us and not attack our own cells.
Dr. Michelle McMurry-Heath (17:08):
As we heard from Dr. Miller, mRNA vaccines for COVID-19 are not the only options we have. Vaccines developed with very different technology have been around since Edward Jenner's experiments with a smallpox vaccine in 1796.
Silvia Taylor (17:25):
Our vaccine has been approved in markets all over the world. We have authorizations that if you look at it in terms of potential lives covered, 6 billion people potentially would have access to our vaccine based on the fact that the vaccine either is authorized in their market or is covered under WHO emergency use listing.
Silvia Taylor (17:51):
Our vaccine has been authorized so far in Europe, Canada, Australia, New Zealand, Indonesia, India, the Philippines, and additional markets as well. And we're actually already vaccinating people in Indonesia and many countries in Europe, New Zealand, Australia, and in the United States where we have filed for authorization. We hope to get a decision from the FDA soon.
Dr. Michelle McMurry-Heath (18:19):
This is Silvia Taylor.
Silvia Taylor (18:21):
I'm Silvia Taylor. I'm the senior vice president for global corporate affairs and investor relations at Novavax.
Dr. Michelle McMurry-Heath (18:27):
Unlike mRNA vaccine, the Novavax product contains harmless copies of the spike protein of the Coronavirus itself. It works with an adjuvant, which is an ingredient used to strengthen the immune system.
Silvia Taylor (18:41):
Novavax's COVID-19 vaccine is built on a protein based technology platform. This is a tried and true technology platform that has been in use for quite a while in vaccines that people normally take such as for HPV, shingles and influenza. Novavax's proprietary technology platform takes our protein based antigen and add to it our proprietary adjuvant which kind of supercharges the immune response and results in the clinical efficacy of 90% and well tolerated safety profile that we saw for our COVID-19 vaccine in our clinical trials.
Silvia Taylor (19:28):
What also makes our vaccine different is that we do not require being frozen. Our vaccine is stored at standard refrigeration temperatures and distributed using existing vaccine distribution channels. So we also think that's part of what makes it different and is what comes from the fact that we are a protein based adjuvanted vaccine.
Dr. Michelle McMurry-Heath (19:52):
The Novavax vaccine stimulates the immune system to produce antibodies and T-cell immune responses.
Silvia Taylor (19:58):
The adjuvant is the portion of Novavax's vaccine that essentially turbocharges the immune response. Because we have an adjuvant which is a molecule that is added into our vaccine, we're able to use very small levels of antigen, that's the protein based component of our vaccine and generate a durable and higher level of immune response, which we believe translated into the clinical efficacy and safety that we saw in clinical trials.
Silvia Taylor (20:30):
Novavax's entire technology platform is built on being a protein based vaccine. We have a unique approach to it. Our approach is we make our vaccine around a nanoparticle core and then we use our adjuvant. And this is what we have had in use for several decades, where we have been pursuing vaccines for other infectious diseases, such as influenza, and now COVID-19. So it is our expertise and it's how we chose to find a solution to the global pandemic in COVID-19.
Dr. Michelle McMurry-Heath (21:07):
In our discussion with Silvia, she talked about her company's development of vaccines for other infectious diseases.
Silvia Taylor (21:15):
Novavax is a company that has been in existence for 30 years. We have developed vaccines for Ebola, MERS and SARS, vaccines that ended up not getting to market, not being needed after they were developed. We have a phase three study that showed that our vaccine performed very well in influenza. When the pandemic hit, we had to refocus our priorities on the public health needs, which were to focus on COVID-19, but we're moving our vaccine forward in evaluating a combination vaccine with influenza and COVID-19.
Silvia Taylor (21:52):
So that's something we're really, really excited about. Going forward, our technology platform, specifically our matrix M adjuvant is being used in collaborations with other academic institutions and other researchers around the world in therapeutic areas like malaria. So we're really excited about the broad applicability of our technology platform and the progress it holds for other infectious diseases as well.
Dr. Michelle McMurry-Heath (22:18):
We ask Silvia how important it is for people to have multiple options when it comes to vaccines.
Silvia Taylor (22:25):
We believe it is very important for people to multiple options. At the end of the day, we want people to be vaccinated, and we believe that having options is an important driver for people to choose to get vaccinated. Additional options also can help people feel more comfortable with the vaccine that they're taking.
Silvia Taylor (22:43):
And what we have seen in this pandemic is that people are incredibly educated and well versed in different technology platforms and have an opinion of what they want to take and an environment where more vaccines are available and different technology platforms are available. We think that will be an important driver in convincing people to get vaccinated, which is ultimately the end goal.
Dr. Michelle McMurry-Heath (23:06):
More options can lead to more vaccinated people, which in turn brings us closer to normal. It also helps to increase public trust in vaccines and science, which is important when it comes to fighting other diseases or a future pandemic. Thanks to researchers and companies like our guests, we are on our way. Thank you to today's guests and their contributions to advancing science and building a better tomorrow.
Dr. Michelle McMurry-Heath (23:38):
Make sure to subscribe, rate and, or review this podcast and follow us on Twitter, Facebook and LinkedIn at Iambiotech and subscribe to Good Day BIO at bio.org/goodday. This episode was developed by executive producer Theresa Brady and producers, Connor McKoy, Cornelia Poku, and Marilyn Sawyer. Sound design and mixing by Jay Goodman, theme music created by Luke Smith and Sam Brady.