mRNA Technology: The Launch of A New Era for Vaccines?

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Vaccines have worked in the same way since they were invented more than 200 years ago: they use a weakened version of the targeted virus to create an immune response that the body remembers. Since COVID-19 appeared, a new kind of vaccine has emerged -- the mRNA vaccine. The mRNA vaccine is a unique delivery system that focuses specifically on the cells that are the targets of an infection. And, as Robert Salata, MD, UH infectious disease specialist and Program Director, Roe Green Center for Travel Medicine and Global Health, explains, researchers are now studying how to use this revolutionary technology to fight other diseases such as HIV, rabies and influenza.

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Transcript

Macie Jepson

We're talking vaccinations today. A lot of people get them shortly after birth, of course, again before school starts, and sometimes even later in life. Vaccines have actually been around for more than 200 years. Smallpox vaccine was created in 1796. And ever since then, vaccines were pretty much the same. They all used the virus itself in the vaccine.

Pete Kenworthy

Yeah. That wasn't until mRNA vaccines came along during COVID-19, and just the term mRNA got people pretty riled up. With mRNA vaccines came all sorts of widespread misinformation. There was talk about altering DNA in our bodies, the vaccine causing infertility, even putting a microchip inside of us. And while the technology was new to the general public, mRNA has actually been studied for more than 25 years. Hi everyone. I'm Pete Kenworthy.

Macie Jepson

And I’m Macie Jepson. And this is Healthy@UH. mRNA is short for Messenger RNA. And of course, thanks to COVID-19 this technology is now new to the public. But as Pete said, it is certainly not new to scientists. In fact, mRNA has been researched as far back as the early 90s, and modern medicine has some really big plans for it. This is exciting. That's what we're going to talk about today. Joining us to help understand how it works and what the future holds for mRNA based treatments is Dr. Robert Salata, the Physician-in-Chief at University Hospitals in Cleveland, Ohio, and the Chair of the Department of Medicine at UH Cleveland Medical Center. Dr. Salata, thank you for being with us today.

Dr. Robert Salata

Thank you.

Macie Jepson

To give us some perspective on the science behind mRNA, how long have you been working with infectious diseases? And when did you first hear about this?

Dr. Robert Salata

I've been working in infectious diseases for over 30 years. And we've seen pandemics occur, the last of which was related to the 2009 time period when we saw the pandemic influenza outbreak. But we've never seen anything like this before. And the other important thing about this whole phenomena is how amazing and fast the information has been forthcoming. We, within two weeks of its first being described out of China, we knew the full sequencing, that is the makeup of the virus and moved from there. This led to the development of vaccine technologies in rapid fashion. But on the other hand, we keep saying no corners were cut. It was very important that this was done through an international effort. And the science, I think, is what we base our decisions upon, including the use of vaccines for this devastating pandemic right now.

Macie Jepson

We obviously want to talk about how mRNA works, but first let's start with how a viral infection works. What happens with our bodies when we an infection, and specifically what's going on with proteins?

Dr. Robert Salata

So, the role of a virus and its goal in life, so to speak, is to make more virus. And it only can do that if it takes over the genetic machinery of our own cells, and it attaches to and then gets inside of a cell and then takes over that machinery to make more virus. That's really what happens. Every virus targets different types of cells. And in the case of COVID-19, this is directed against our own respiratory cells lining the respiratory tract, et cetera, et cetera. But we know that this can disseminate widely through the body, cause clinical manifestations and such. But it attaches to our own lining cells of the respiratory tract, it gets inside and then makes more virus. Now the key target or component, if you will, of this virus is what is called the spike protein.

This, we have shown pictures of the spike protein, but that's the projections off the surface of the virus. That allows it first to attach to these respiratory cells and then be taken within it, and the process then takes over. So, in retrospect, during the early 2000s, when we knew about SARS-1, as well as subsequently the MERS virus, another coronavirus in the Middle East, we found that when people developed protective immune responses against the spike protein, this was protective against subsequent infection. And indeed, the spike protein remains the major component of the virus that we target our vaccines upon. And in the cases of the mRNA, this is used to attach to the spike protein of the virus, and then it is delivered to the cells. It has protective layers, because if you don't have that in place, some of which probably have been related to some of the allergic reactions among other things, then this would be rapidly destroyed as soon as it's injected.

Therefore, it gets inside the cell because it has this protective layer. But once it does, that is removed, and our own cell products destroy the mRNA. So, one of the things that people have been concerned about is whether or not this RNA, genetic code so to speak, is incorporated forever. And that is not the case. It is destroyed rapidly. But it delivers the goods, so to speak. So, the spike protein then is expressed on the outside covering of the cells, and that's what the immune system sees and to which there are two types of immune responses that occurs. One is the so-called antibody response, which has been most written about, and that's very important. And the other are T-cell responses. And these are even longer lasting. And we don't know yet the full impact that these T-cells have on protective immune responses, but they probably are very important in addition to the antibodies. So, that's how this works. But viruses, and by the way, with your opening comments, we also have plenty of vaccines that are directed against bacteria as well. So, all these microbes. And it's revolutionized the whole approach to prevention of infection around the world. And this one, particularly with regard to the use of COVID vaccines, has done the same.

Pete Kenworthy

So, mRNA, it sounds like from what you were saying, it's almost like a delivery van, right? It comes in, it brings what you need into your body and then it gets destroyed, right? So, how does that compare to the vaccines we were used to, right? We were used to when you were injected with the dead or the weakened virus, like the flu vaccine, right? So, how is that different from mRNA vaccines?

Dr. Robert Salata

Well, it's this unique delivery system that's very different in terms of what we've seen before. But because we can deliver the goods, as I said before, get them expressed on the very cells that are the targets for the infection, this really has been a revolutionary approach in terms of how we've approached vaccinology. And we'll talk about this later, but there are many applications of this technology now that we know it works, and it's well tolerated for the most part in terms of other infectious diseases and even outside of infections, how we might use such technology.

Pete Kenworthy

But previously, if you look at like the flu vaccine or other vaccines that used dead or weakened virus, how did that work? Just so I understand the difference.

Dr. Robert Salata

In a similar way. Again, it would cause an immune response, but not so elegantly as this does with regard to being incorporated into the very cells which are the basis for the infection of the COVID-19. So, that makes it different. Whereas in these other cases, we're just relying upon the vaccine, you know, even without it being delivered on those very cells to the immune system, and you get immune responses that way. So, this really has been a major advancement, I think, in terms of vaccines and will be applied in other circumstances.

Pete Kenworthy

And because it's so targeted, we hear about this 95 percent, you know, 95 percent of people who got it are protected. And you talk about the flu vaccine, you're talking 30 to 50 percent, right? So, it's a game changer.

Dr. Robert Salata

It is.

Macie Jepson

I really want to talk to you about this influenza and this being a game changer. And we're going to get to that in just a moment. But let's go back to what you said about changing DNA. I think it's really important for us to stress this because that's what we've been hearing. And yet people still say, nuh-uh. How do you know? So, let's discuss that and any other myths that concern you, Doctor.

Dr. Robert Salata

Well, this is an important point because many people still live with the idea that this is changing our genetic makeup. This is an RNA, so it's different from DNA. So, it has nothing to do with that. There are other vaccines in the COVID armamentarium such as the AstraZeneca vaccine that's used outside the United States, but also Johnson and Johnson, which are DNA-based viruses. And it's using another virus called adenovirus to deliver the goods into which the genetic material from the COVID virus is packed or inserted. So, this does not change DNA in any shape and form. As I said, it's destroyed. We've looked at this in animal models and also in the initial volunteers that have received the vaccine for any telltale sign of the, of any remaining RNA, messenger RNA. We've also looked at transmission through the placenta in women who are pregnant. So, we have not seen any of this happening. And for that matter, many of the other myths, since you're talking about this, Macie, related to infertility, et cetera, were suppositions by a few so-called scientists about this phenomena, but it's never been shown to be the case. So, it has been studied extensively now in over 20,000 women, particularly if given in the third trimester, and it's not been shown to affect any element of the reproductive capacity in these women then or subsequently.

Pete Kenworthy

So, we mentioned this is not new technology, that it started in the early 90s. And it was since studied to fight things like you mentioned, influenza, Ebola, SARS, but it didn't work out then for those. Why not? Why didn't it work before?

Dr. Robert Salata

I don't think we had all the technology down at that time. Plus we have to be really cognizant of the type of infectious agent we are dealing with. We have subsequently had more successful vaccines against Ebola, for instance. We use influenza vaccines all the time, although we're still searching for one that will be given and will be effective for over a much longer period of time than on an annual basis. In part, and this applies to COVID as well, we see changes in the influenza virus all the time. And that change or mutation with influenza can be sometimes subtle or major. And if it's major and not a great many people have been exposed to that form before, we are set up for an epidemic, which happened in 2009.

Macie Jepson

Let's fast forward to 2017. There were human trials underway for mRNA vaccines, HIV, influenza, Zika, rabies. Scientists were moving the needle at that time, it seems. Was it because those human trials were already underway that science was able to move so quickly for COVID-19 vaccines? I mean, I imagine quick funding had a little bit to do with it as well.

Dr. Robert Salata

Quick and ample funding was an important step in that regard and also cooperation among many, many countries and scientists around the world. But because this technology was already advanced to a point, we were able to take advantage of that, all that previous work and incorporate that into the design of mRNA-based coronavirus vaccines.

Pete Kenworthy

So, it sounds pretty awesome, really what science is able to do here. And looking at the future of mRNA vaccines, treatments, we've mentioned human trials already underway, right? HIV, rabies, influenza, but I've also read about malaria tuberculosis, hepatitis B, Cystic Fibrosis. I mean, it sounds truly amazing, but is it? I mean, are the possibilities really limitless for this technology?

Dr. Robert Salata

We have to take baby steps here. Yes, the technology is really easy to work with, and if you want to change it from one bacterial or viral process to another, you can do that relatively easily. We are going to undertake relatively soon a trial phase one trial, which is the earliest form of human investigation for vaccines and other products like that, where we're going to be mainly focused on safety and looking at an influenza vaccine that is linked to the mRNA technology. And we think this may provide the opportunity to have a more effective vaccine because of how this works, again, which we discussed before. Because as you mentioned, Pete, the efficacy rate on an annual basis of flu vaccine is on the order of 30 to 50 percent. We need to improve that.

Macie Jepson

We've been talking a lot about viral infections, so I may be off-base here, but I just, this seems like the superstar of the future. So, we, I have to ask about cancer treatments. Is that even on the horizon?

Dr. Robert Salata

So, to have targeted treatments for cancer is really what we want to do, and therefore avoid all the so-called collateral damage that occurs with our own cells in our body that is rapidly dividing. And that's what happens with current chemotherapeutic regimens, that there are other cells that are by-standers of the effect. So, if we can target this more so, we're doing some of that now with immune-based therapies in the context of cancer, this will be revolutionary. And mRNA was first being developed at the outset for the purposes of cancer therapeutics. So, I think we'll see a return to that. And I am saying right now that some of the folks originally involved in the development of the mRNA technology, including then and now, will likely be Nobel Prize winners in the end.

Macie Jepson

Wow.

Pete Kenworthy

That's incredible to think about. I'm guessing, and you mentioned ample funding when we said funding, but I'm guessing that's a huge part of it, right? I mean, for any of this development, it was the funding, the ample funding you mentioned was quickly available during a global pandemic. Obviously, everybody was on the same page there. But for these other things that we mentioned, the whole world may not be working together as we did during COVID-19. Is that the stumbling block for whether it's for cancer or Hepatitis B, Cystic Fibrosis, at any of these things, is the stumbling block the funding, or is it the technology itself? Or both?

Dr. Robert Salata

The funding will be a challenge, but I think as this has been so successful in the context of COVID vaccine development, that you'll see a significant willingness by the funders, including the National Institutes of Health, to make these resources available for further development.

Macie Jepson

Well, one thing is certain … mRNA is not a foreign term to the public anymore, and the future looks bright for use in a lot of ways. Dr. Robert Salata, Physician-in-Chief at University Hospitals in Cleveland and the Chair of the Department of Medicine at UH Cleveland Medical Center, thank you so much for joining us today.

Dr. Robert Salata

Thank you, Macie and Pete.

Macie Jepson

And remember, you can find and subscribe to this podcast on iTunes, Google Podcasts, Stitcher or wherever you get your podcasts. Search University Hospitals or Healthy@UH depending on where you subscribe.

Pete Kenworthy

For more health news, advice from medical experts and Healthy@UH podcasts, just go to UHHospitals.org/blog.