JN.1 Monovalent mRNA Vaccines: Antiviral Humoral Immunity

Welcome to the Heliox Podcast, where we dive deep into the fascinating world of COVID-19 vaccines and immune response. In this episode, we unravel the complex dance between virus variants, vaccine technologies, and our body's immune system. Join us as we explore cutting-edge research on how new vaccines are adapting to outsmart evolving viral threats, revealing surprising insights about immune memory, antibody responses, and the potential for more universal vaccine strategies. It's a journey through science that offers hope and understanding in our ongoing battle against a constantly changing virus.

Robust antiviral humoral immunity induced by JN.1 monovalent mRNA vaccines against a broad range of SARS-CoV-2 Omicron subvariants including JN.1, KP.3.1.1 and XEC ( Sato Lab )
https://www.biorxiv.org/content/10.1101/2024.11.20.624471v1

Transcript

0:00

New COVID variants in late 2024, huh? I feel like we just can't seem to shake this virus. Yeah, it does feel that way sometimes. But hey, that's why we're here. That's right. To dive into some fresh research today, straight from Biorxa. Straight from the source. A pre-print, actually. Oh, right. You always got to remind me. Meaning it hasn't gone through the whole peer review thing just yet. Yeah, yeah. So we're getting like a sneak peek, huh? And some cutting-edge science. I always feel like it's a little more exciting to be in the know early, you know? Oh, absolutely. So this paper, it tackles this question of how effective these new JN1-based mRNA vax ones are. These new vaccine? Against, well, all these latest Omicron sub-variants. It seems like there's always new ones, right? Always, yeah. They're spreading like crazy. They are. Specifically, we're going to be looking at the ones from Pfizer-BioNTech and Daiichi Sankyo. Okay, sounds good. I think the reason these new sub-variants are causing such a stir is because they're so good at dodging our immunity. Right. The immunity that we've worked so hard to build up from previous infections, vaccinations, all of that. Right. Like they're evolving specifically to sneak past our defenses. Exactly. The virus is constantly changing. It is. And our immune systems are always playing this game of catch-up. Okay, so the study, how did they even do it? Well, they took blood samples from people. Okay, normal. Yeah, before and after they got either the Pfizer or the Daiichi Sankyo JN1 vaccine. So two separate groups? Two groups, yeah. And what's interesting here is that the Daiichi Sankyo vaccine, it uses a slightly different approach. Oh, how so? It only uses what's called the receptor-binding domain of the virus's spike protein. Oh, okay. It doesn't use the whole thing like the Pfizer vaccine does. I need an analogy. Okay, imagine the spike protein is like a key. And the receptor-binding domain is the part that actually fits into the lock. Okay, got it. And that lock being a receptor on one of our cells. So the Daiichi Sankyo vaccine, it's like a smaller key. Yeah, it's more targeted. Well, minimal. Exactly. And so this raises the question, right, does using a smaller key impact how well the vaccine works against these new variants? Oh, that's a good question. It's like the size matter. Right. When it comes to vaccines, well, the results might actually surprise you. Oh. Both vaccines significantly boosted antibody levels. That's great. Against all the variants they tested. Okay, but I need specifics. How much of a boost are we talking? Okay, so the Pfizer vaccine, it showed a 2.4 to 8-fold increase in antibodies. That's pretty good. And get this, the Daiichi Sankyo vaccine, even with the smaller key, it showed an even bigger jump. Really? Between 2.3 and 13-fold. Wow, that's significant. Yeah. So it seems like the minimalist Daiichi Sankyo vaccine, it really held its own against the Pfizer, huh? It did, which is really fascinating. Yeah. Because it challenges this idea that we've had that maybe a more complex vaccine is always better. Right? Right, right. So it opens up possibilities for simpler, more cost-effective vaccines maybe in the future. Yeah, that's a total game changer. Of course, every study has limitations. That's right. We always have to be cautious about interpreting the results too broadly. So what are some things we should keep in mind with this study? Well, they did have a relatively small sample size. Okay. It was less than 20 people in each group. I see. And they also didn't really account for factors like a person's age or their previous infections. Right. Or their overall health, really, which could influence things. Of course, yeah. So more research is definitely needed to confirm these results, but this is exciting stuff. Absolutely. Now, this is where it gets really interesting, I think. Okay, I'm listening. The paper, it also compares how well the vaccines work to what happens when someone just gets infected naturally with these sub-variants. Okay, yeah. And this is where things get a little weird. Okay. The study suggests that getting infected with these JM.1 sub-variants might actually lead to, well, weaker antibody protection than if you got the vaccine. So the vaccine may be better. Yeah. Isn't that kind of counterintuitive? Like, don't we usually think of natural immunity as being the strongest? That is what we usually think, yeah. This study really challenges that notion. So why would a vaccine be potentially offering better protection than actually getting infected with the virus? Well, it's not totally clear from this study alone, but we can speculate a bit. Let's hear it. Maybe the vaccine, because it delivers the antigen in such a specific way, it's better at, you know, training our immune system compared to, like, the chaotic environment of a natural infection. So it's like a personal trainer for our immune system. Exactly. I like that. And this is really important because it has implications for, you know, public health messaging. Sure. It emphasizes how important vaccination is, even if you've already had COVID. Yeah, that's really interesting. Now, you mentioned something earlier called immune imprinting. Oh, yes. Can you explain what that means? Sure. It means that our past exposures to viruses, well, they shape how our immune systems respond to new variants in the future. Like our immune system has a memory. Yeah, exactly. And this study hints at how that memory might be playing a role in how effective these new vaccines are. So it's like our immune system is carrying this backpack full of experiences. I like that. And those experiences can either help or hinder its ability to adapt to these new challenges. That's a great way to put it. And this leads us to another weird observation from the study. OK, tell me more. The researchers found that the JN.1 vaccine, while not specifically designed for the XBB.1.5 variant, it actually did a better job at generating antibodies against it than the XBB.1.5 vaccine itself. And how is that possible? Yeah, I know, right? I mean, it suggests that maybe previous exposures to other Omicron variants might have primed the immune system to respond better to XBB.1.5. Even though it wasn't an exact match? Even though it wasn't an exact match, yeah. So our immune history is kind of influencing how well these vaccines work against new variants. It seems like that's what this is pointing to. It's all so complex. It really is. Yeah. And it raises a big question for the future of how we make vaccines. If our immune history matters this much, what does that mean for how we design and actually give out the vaccines? That is the question. And that's a question we're going to delve into further in part two of our deep dive. I'm ready when you are. We'll be back after a short break. OK, sounds good. To explore those implications of immune imprinting and all the strategies scientists are considering to overcome this challenge. Should be interesting. Stick with us. Absolutely. So we're back diving deeper into these JN.1 monovalent mRNA vaccines. Back at it. Yeah. Before the break, we were talking about this whole idea of immune imprinting. Right. Our immune system basically developing a memory. A memory of all its past encounters with viruses. And how that memory could actually be impacting, you know, how effective these new vaccines are against all these emerging variants. It's like, OK, our immune system has this backpack full of all its past experiences. And sometimes those experiences, well, they can help. But sometimes they hinder its ability to, like, adapt to new challenges. Yeah. It's a fascinating area of study. It really is. And it makes you wonder, what does all this mean for the future of how we develop vaccines? You know? Right. If we have to think about everyone's unique immune backpack. Yeah. How do we even begin to design vaccines that are going to offer, like, broad protection to everyone? That's the big question, isn't it? It seems like the really monumental task. Like, we're trying to predict the future of how these viruses are going to evolve. Right. But scientists, they're exploring different approaches, you know, trying to get ahead of it. OK. Like what? Well, one strategy is to develop vaccines that, you know, offer broader protection. OK. By targeting the parts of the virus that are less likely to mutate. So instead of, like, chasing after every single new variant with a specific vaccine. Yeah. We could try to make something more universal. Exactly. Something more universal. So not like what they're trying to do with the flu vaccine. Precisely. Like, if we could just identify and target those parts of the virus that are more stable. Yeah. We might be able to develop a vaccine that would offer more durable protection against a wider range of variants. Even the ones that haven't even emerged yet. Yeah, that's the hope. That would definitely make things simpler, but it sounds really hard. It is very challenging. Like, how close are we to actually achieving that? It's still pretty early, I would say. OK. But there are definitely some encouraging things happening. Like what? Well, researchers are looking into different vaccine platforms. Yeah. Including, you know, what are called nanoparticle vaccines. OK, I've heard of those. Which could potentially deliver multiple antigens from the virus all at the same time. So instead of just giving our immune system, like, one target to practice on, we'd be giving it an array of targets. Exactly. OK, interesting. What about those mucosal vaccines that I keep hearing about? How do those fit into all of this? Oh, mucosal vaccines. Those are really interesting. Yeah, tell me more. So unlike traditional vaccines, which are injected into the muscle, mucosal vaccines are delivered through, like, the nose or the mouth. OK, and why is that important? Well, think about it. The mucosal surfaces, like in our respiratory system, that's the main way the virus gets in, right? Yeah, that makes sense. So by delivering the vaccine directly to those surfaces, we could potentially stimulate, like, a more targeted immune response right where we need it. OK, so instead of waiting for the virus to, like, get into our bloodstream and then our immune system's like, "Oh, I've got to fight it off," we're meeting it head on right at the border. Exactly, like border patrol for our immune system. I like that. Mucosal vaccines, they could potentially even prevent infection altogether, not just reduce how bad the disease is. Wow, that would be amazing, a total game changer. Yeah, there's a lot of potential there. It sounds like there's a ton of potential. With all these new vaccine technologies, it's pretty exciting. But let's get back to the study we're talking about, right? This research, it wasn't about nanoparticles or mucosal vaccines. Right. But it did show something really interesting about that Daiichi Sankyo vaccine. Oh, you mean how it uses just the receptor-binding domain of the spike protein? Yes. And it still, like, created a really strong antibody response. Right, it was really effective. I have to admit, I would have thought that you needed the entire spike protein to get a good immune response. It seems logical, but this study suggests that maybe sometimes a more targeted approach is just as good. Or even better. Yeah, potentially even better. And by focusing on that receptor-binding domain, you know, that key that lets the virus in, we might be able to stimulate a more precise and more powerful immune response. So it's not just about brute force. It's not. It's about precision targeting. I like that, precision targeting. Okay, I want to talk more about this whole immune imprinting thing. Yeah, let's do that. Because it seems like it's playing a big role in all of this. It really does. You mentioned that our immune system has this memory. And sometimes that memory can be a double-edged sword. Right, it can protect us from viruses we've seen before. Yeah. But it can also make it harder for our immune system to adapt to new variants. It's like our immune system gets stuck in its ways. It does, kind of clings to its initial impressions. Even though the virus is changing all the time. Exactly, and that's why it's sometimes called, you know, original antigenic sin. Original antigenic sin. That sounds kind of biblical. It does, doesn't it? Yeah. But it basically means that our first encounter with a virus, it can leave like a permanent mark on our immune system. Interesting. And that initial imprint, it influences how our immune system responds the next time it sees a similar but slightly different version of that virus. So our immune system can't really learn new tricks. It can be tough to teach an old immune system new tricks. And that makes developing vaccines really hard. Especially when you're dealing with a virus that mutates as fast as this one. So how do we design vaccines that can overcome this original antigenic sin? Well, scientists are working on it. One approach is to include like multiple antigens in the vaccine. Okay. So it represents a bunch of different variants. Oh, I see. So it's like we're showing our immune system a photo lineup. Yeah, like a photo lineup of all the suspects. So it's prepared for anything. Precisely. We're broadening its recognition skills. Okay. And are there any other strategies? There are, yeah. Another one is using what are called adjuvants. Adjuvants. Remind me what those are again. They're basically substances that we add to vaccines to boost the immune response. Like booster rockets. Exactly. Booster rockets for the immune system. They help amplify the immune system's reaction to the vaccine. Okay. So it's like we're giving our immune system a little extra help. Yeah, to break free of those old habits and learn something new. To learn some new tricks. And there are a lot of different adjuvants being tested right now in clinical trials. And some of them are looking really promising. It's amazing how much work is going into developing these new vaccines. It really is. Very inspiring. Now, remember that surprising finding we were talking about earlier? About? The JN1 vaccine being better against the XBB.1.5 variant than the XBB.1.5 vaccine. Oh, yeah. Yeah. That was a weird one. Well, it turns out that might be another example of immune imprinting at work. Really? How so? So the people who got the JN1 vaccine, maybe they had been exposed to other Omicron variants in the past. Okay. That were more similar to XBB.1.5. So their immune systems were kind of already primed. To recognize and fight off that new variant. Yeah, even though they hadn't seen that exact variant before. So their immune history was giving them an advantage. It's kind of like we're all walking around with these unique immune histories. Yeah. Shaped by all our past encounters with these viruses. And that makes it really hard to predict how any individual is going to respond to a specific vaccine. Yeah, it's like trying to predict the weather. Right, you can have all the data in the world, but there's always going to be some unpredictability. Okay, I see your point. That's why this research and all the monitoring is so important. It is. We need to keep learning more about these vaccines, how the virus is evolving, and how our immune histories are factoring into all of this. Exactly. It's a complex puzzle. But at least scientists are making progress, right? They're starting to understand all the intricacies of this virus. Absolutely. And all those efforts, they're paving the way for new and better vaccines in the future. Yeah, I hope so. We've covered a lot in this segment, from the challenges of this immune imprinting to all the potential of these new vaccine technologies. We have. But before we wrap up this part of our deep dive, let's touch on one last thing from the study that we haven't really talked about yet. Okay, what's that? They noticed that the antibody response to the J.M. Mose 1 vaccine, it actually varied a lot from person to person. Oh, yeah, that's interesting. And that's something that researchers really want to understand better. Why are some people responding so much better than others? So even though the study showed that overall antibody levels went up, some people might have a much stronger response than others. Exactly. And that leads to a bunch of new questions. What are the things that cause this variability? Can we even predict who will respond best to a certain vaccine? And can we, you know, tailor vaccine strategies to get the best response from each person? Wow, that's a lot to think about. It is. These are all really important questions that researchers are trying to figure out. And in part three of our deep dive, we're going to dig into some of those latest findings. Sounds good. And explore what this means for, you know, personalized medicine and the future of vaccine development. I'm looking forward to it. We're back, ready to wrap up our deep dive on these J.M. Mose 1 vaccines. It's been quite a journey, hasn't it? Unpacking all this new research. I know, right? So much to learn about these vaccines and, well, how our immune systems are dealing with this constantly changing virus. It really does feel like every time we think we're getting a handle on things, the virus throws us a curveball. It does, but that's what keeps things interesting, right? It certainly does. It's like this constant challenge to stay one step ahead. I like that. In the last part, we were talking about how people can have such different responses to the same vaccine. Right. Some people have a really strong immune response. Right. While others, not so much. And that makes it hard to know for sure how well a vaccine is going to work for everyone, right? It does. So as we wrap up, I want to kind of zoom out a bit. Okay. What are the big takeaways from all this research? Okay. Good question. I think one of the most important things we've learned is that these new JN1-based mRNA vaccines, they're looking pretty good against those latest Omicron sub-variants. That's good news, especially with winter coming up and all. Exactly. When those respiratory viruses really like to spread. For sure. And it's really interesting that the Daiichi Sankyo vaccine, the one that uses just the receptor-binding domain. Right. That smaller key. It's working just as well as the Pfizer vaccine, which uses the whole spike protein. Right. Which is really promising. Yeah. Because it could mean we can get the same protection with simpler and probably cheaper vaccines. Which is a huge win, especially for getting vaccines to everyone around the world. Absolutely. It could make a big difference for global health. And then there's that really surprising finding about natural infection. Oh, yeah. That one was a head-scratcher. It seems like actually getting infected with these new sub-variants might not give you as much protection as getting the vaccine. That's right. And it really challenges what a lot of people think about natural immunity. Yeah. I mean, you always hear that natural immunity is the best. Right. But this research is suggesting that might not always be the case. So even if you've had COVID, getting vaccinated is still really important. It is. OK, we can't talk about these vaccines without bringing up immune imprinting again. Immune imprinting, it really is the big story here. This idea that all of our past run-ins with viruses, they're shaping how our immune systems are dealing with these new variants. It's like our immune system has developed its own unique way of seeing the world. Based on its own experiences. Exactly. And that can be a good thing. It can protect us. Right. But it can also make it harder for our immune systems to adapt when new challenges pop up. Yeah. Like it's got a certain mindset and it doesn't want to change. And that's why we need to keep doing research on this. Yeah. To figure out how immune imprinting works and how we can use that to design even better vaccines. So where does all this leave us for the future of vaccines? Are we going to have to constantly update them for every new variant that comes along? That's the question everyone's asking, isn't it? It is a big question. Can we actually outsmart this virus and create a vaccine that just works, period? It's the ultimate goal. Right. And there are a lot of smart people working on it. Well, that's good to hear. One idea is to design vaccines that focus on those parts of the virus that don't change as much. So instead of going after each new variant. We target something more fundamental. Exactly. Something more stable. Like we're building a foundation that can handle anything. I like that analogy. Another idea is to make vaccines that can trigger a broader immune response. So they're going after multiple parts of the virus at the same time. Right. And that could help overcome those limitations of immune imprinting. Makes sense. And we've talked about those nanoparticle vaccines. Yes. And the mucosal vaccines. Right. Those are exciting areas. It seems like there's a lot of potential there. There is. With all these new technologies and all this new research, I'm feeling pretty optimistic. Me too. Like we might actually be able to get ahead of this virus. I think we're getting closer all the time. I think we've covered pretty much everything in this deep dive. I think so. We've gone from the nitty gritty of this study to, well, all the big implications for how we develop vaccines in the future. It's been a good discussion. I hope our listener is walking away with a better understanding of these new vaccines. Me too. And maybe a little bit of hope for the future. A little bit of hope. Definitely. I do want to say, though, that research is always ongoing and we're constantly learning new things about this virus. Right. It's always changing. But one thing's for sure, vaccination is still one of the most important tools we have in this fight. It's our best defense. So as we leave our listener today, we want to leave them with this question. If our immune history is so important, what does that mean for you? That's a good question. As new variants and new vaccines keep coming out, how are you going to factor in your own immune history when you make decisions about your health? Something we all need to think about. And we encourage our listener to stay curious, stay informed. Absolutely. And keep those conversations going with their health care providers. It's the best way to make the decisions that are right for you. Well, that's it for this deep dive. Thanks for joining us. Thanks for having me. Until next time, stay healthy, everyone.