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mRNA Technology in Vaccines


Vaccine mRNA technology has revolutionized the vaccination landscape.

James Lewis, PharmD, FIDSA: ThemRNA technology for vaccines is really different from the other platforms we’ve seen historically. It causes the body to produce a structure that’s a key component of a virus that you’re trying to go after. For example, take the COVID-19 mRNA vaccines. A piece of mRNA was encoded and injected as part of the vaccine, and it went into the cell and caused it to produce the spike protein of COVID-19. You didn’t take a chunk of the virus. You didn’t take a live virus and kill it. You didn’t take a chunk of the virus and conjugate it into a protein. You actually cause the body to make a little key structure of that virus by having mRNA get translated into the patient’s cells. It’s a slick and brilliant way to do this. Also, it creates a situation where you don’t have to inject the whole virus or worry about partially killing things. It’s really slick, and it’s amazing.

One of the reasons we’ve been excited about mRNA technology for flu vaccines for a long time is that it’s very easy to change the vaccine. We’ve seen this with the boosters and the omicron boosters with COVID-19. If we had tried to do that with conventional vaccine technologies, it would have been a lot harder to change that vaccine. But the mRNA technologies allow you to swap in templates for that mRNA very quickly. You can modify vaccines very quickly to go after things that have evolved or changed. One reason the mRNA technologies are so exciting is because of the flexibility of that platform. The speed with which you can change the platform is like something we’ve never seen. That’s why it’s nicely fitted to an influenza vaccine that you need to change every year. You don’t have to worry about whether the virus grows in eggs. With the flu, every year, we all hold our breath: “I hope the virus grows in eggs. Please grow, please grow.” You don’t have to worry about the virus growing. If you have a virus that grows poorly, if you have a virus that’s hard to get your hands so you can work with it, you just need the sequence. Then you can build an mRNA vaccine just from that. [It offers] lots of flexibility, speed, and customizability. The technology is amazing. The opportunities that it presents are a huge step forward over what we’ve had historically.

The 3 vaccines we’re going to see the soonest will be RSV [respiratory syncytial virus], CMV [cytomegalovirus], and influenza. We’re going to see an RSV vaccine very quickly. I expect to see a CMV vaccine in the not-too-distant future. Although we need to wait and see, the phase 3 study is ongoing. I haven’t seen top-line results on it. CMV has proven to be a nasty little beast in the past to get under control. I’m cautiously optimistic that the mRNA vaccine in development for it will be successful. The third thing you’re going to see in the near future will probably be an mRNA influenza vaccine. Those are going to be the 3 things, over the next year or 2, that you have a high probability of seeing in this space. There are certainly other disease states I’m less familiar with, but there are other things that the mRNA platforms are investigating.

In the noninfectious disease space, could mRNA vaccine technology be useful for treating cancers and whatnot? That question is generating some real interest. This is a space that bears watching over the next 5 years. COVID-19 fast-forwarded [mRNA] technology, which has been proven to work and is safe. We’re getting better. One problems with mRNA is that it’s not stable. You saw that with how cold you had to keep the COVID-19 vaccines originally. It’s not easy to work with, but we’re getting better at finding ways to stabilize the mRNA. There’s a lot of opportunity, and it’s a very fast-moving field.

This will be a really interesting space: how the evolution of mRNA vaccines could improve outcomes for patients that payers might be worried about. Let’s take influenza and RSV because they’re going to come online fairly soon. We have good data for the impact of those viruses in populations that payers are going to be worried about. Every year, influenza results in [tens of thousands of] hospitalizations, interactions with health care, and whatnot. Having an mRNA-based influenza vaccine is better in efficacy…. You may have an mRNA vaccine for influenza. The question is, will its efficacy be better than what we see? That’s what we need: something that improves efficacy. I’m less clear that an mRNA vaccine, as it stands, would improve in efficacy over what we’ve got. That’s an important piece. But influenza vaccination keeps people out of the hospital, cuts down on missed days at work, cuts down on doctor visits, is an antibiotic steward, and cuts down on antibiotic use. There are a lot of things to love about a properly influenza-vaccinated population.

This is a reason that payers need to think about what they can do to ensure vaccinations. Everybody in the United States over 6 months old is recommended to get a flu vaccine every year. We’re not there. We’re not even close. Unfortunately, COVID-19 did a number. It’s going to be very interesting to see what our influenza vaccination numbers look like for the last year or 2. I have a bad feeling they’re going to look like our numbers at OHSU [Oregon Health & Science University], which isn’t good. As a health care system, we need to think about how can we effectively communicate to our patients that this is important, that it is safe and does work. That same messaging is so important for health care providers, societies, organizations, and developers of content for continuing medical education. We need to get this message to our frontline health care providers. I’m amazed at what’s happened in the last 2 to 3 years, with people getting so much misinformation from the internet and social media about vaccines. That includes flu vaccines. We’ve got a new struggle in that space. We already weren’t doing as well as we could have or should have.

RSV is also going to be tricky because it’s thought of as a pediatric problem. But the data clearly show that it’s an adult problem also, especially over age 60. Looking at the impact of RSV, if you prevent severe disease and hospitalization, that’s a win. From a cost perspective, that’s a win all day, every day. It’s certainly a win clinically. Influenza and RSV are the 2 spaces that I’d encourage payers to take a long, hard look at as we move forward. You’re going to see an mRNA vaccine for RSV—you’re definitely going to see an RSV vaccine pretty soon. With influenza, we’ve still got a lot of work to do. We’ve got a lot of work to build back the faith and trust of society in this vaccine. We need an influenza vaccine that works better at preventing disease than 50% to 60% vaccine efficacy, which the CDC [Centers for Disease Control and Prevention] reports every year.... A lot of times those numbers are in the 35% range. There’s definitely a lot of room for improvement.

Transcript edited for clarity.

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