Episode 38: Unveiling T-Vant - Tulane's Revolutionary Vaccine Adjuvant with Key Opinion Leaders Lisa Morici and James McLachlan (RE-RELEASE)

If you're in vaccine development, you will not want to miss out on our episode of BIO from the Bayou, where we discuss T-Vamp, one of the latest advancements in vaccine adjuvants.

You're listening to BIO from the Bayou, featuring stories and industry insights from experts in the bustling biotech scene of New Orleans. The entire Gulf Coast region is buzzing with expertise and excitement, and we're here to bring you frontline access to this vibrant ecosystem direct from NOLA. The city that provides a little Lagniappe with everything we do. Where people come for the science and stay for the food, festivals, and resilient culture. I'm Sharon Courtney, Vice President for Government and Community Relations at Tulane University. And I'm Nicole Honoré, Assistant Vice Chancellor for Economic Development and Strategic Initiatives at LSU Health New Orleans. And this is Bio from the Bayou.

Welcome back to Bio from the Bayou. My name is Elaine Hamm, and I am the Executive President For Tulane School of Medicine, and today's guests are Dr. Lisa Marici and Dr. James McLaughlin. Lisa is a professor of microbiology, and James is an associate professor of immunology, both at Tulane University School of Medicine, and they are here to talk about their new vaccine adjuvant, what we call Tvant. But before we dive into it, I love asking people's why, because, well, you guys know science is hard, and the whys are what keeps us moving forward. So I'd ask Both of you, why vaccines? Why adjuvants? Why do you do what you do and what drives you?

It's a good question. And I think many of us ask ourselves that question quite a lot. I think for me, the reason that we chose— I sort of happened into adjuvants. I'm an immunologist by training, so I like to understand how the immune system works and really how it works in response to infections, viruses, and bacteria. And so I think The reason that I ended up landing on vaccines is in my attempt to understand how the immune system responds to infectious disease, I realized that we just don't have many, or as many good vaccines against a lot of infectious diseases. And the ones that we do have, many of them are not good enough. And so I think I sort of came to this with a desire to understand how infections work, and as a result, understand how we can make better vaccines. To combat those infections and ultimately to improve human health. I think that's why we all are in this, I suspect, those of us that are doing this, is to make people better and healthier.

Same question to you, Lisa, then. Why do you do what you do? What drives you?

Yeah, it's a great question. You know, James just talked about how he's trained as an immunologist, and my training is in microbiology, and particularly infectious diseases. Looking back over the history of humankind, I think, you know, the impact of infections on human life expectancy, you know, is not really appreciated by the newer generations who aren't as impacted until the recent SARS-CoV-2 pandemic. They weren't really impacted by infectious diseases like our grandparents were, or even our ancestors. And, you know, it's fascinating that, you know, vaccine development and really the introduction of vaccines into the human population, you know, there's probably been no greater impact on the increase in human lifespan than the development of vaccines, other than perhaps access to clean water. And so to work in this field, it, you know, it's very inspiring to see your hard work pay off in the form of a vaccine that could then go on to save lives. And, you know, working with James has been just, you know, such a fun experience, because together as a microbiologist and James is an immunologist, we're able to tackle vaccinology from 2 different angles, from the side of the host as well as the side of the microbe, and that's been a lot of fun.

Oh man, you totally stole my line. I was going to say this sounds like the perfect collaboration between an immunologist and a microbiologist. That's great. I think that's why you guys make such a good team. You cover all the bases. All right, well, let's dig into the more science side of things. Let's talk about what a vaccine adjuvant is. I think most people know what vaccines are, but What is a vaccine adjuvant?

Okay, so I guess I'll take this one as the card-carrying immunologist in the room. So I want to preface this by saying the immune system is pretty clever, anthropomorphically speaking, and has evolved a variety of mechanisms to be very careful about responding to things that are dangerous, so bacteria, viruses, funguses, parasites, and has been Evolved very carefully to not respond to things that aren't dangerous, like ourselves, right? So we don't want to respond to our own bodies, but we very much want to respond to things that are dangerous, like infections. So the immune system has evolved to respond to infections, but if you give a piece of a bacteria or virus, generally what we're trying to do is give small pieces to stimulate an immune response. And the problem is, if you give a small piece of a virus or bacteria, The immune system has learned that that's not that dangerous, and it's not something it wants to respond to because it's trying not to respond to yourself. So it doesn't need to respond to small things like that. So one of the things, one of the ways we can sort of trick the immune system into responding to those pieces of viruses or bacteria is to give this sort of extra bit of an immunostimulatory component that then sort of tricks your immune system into thinking, oh, that piece of that bacteria or virus is actually—

Dangerous.

Something I do want to respond to. And that is what we call an adjuvant. So that's just something we add to a vaccine to sort of make your immune system want to make an immune response. And the really important part of the immune system that I think is worth thinking about or remembering for these particular vaccines is that the parts of the immune system that we are really interested in are the ones that remember things. And so all your immune system doesn't remember everything, but 2 major parts of your immune system Remember what they see. And again, this is a little bit anthropomorphic, right? We're not talking about— they don't literally remember. They don't have brains, but they undergo a series of genetic changes. This is evolutionarily conserved over billions of years so that if you respond to an infection like a virus or a bacteria, the immune system, that part of your immune system remembers that it's seen that, and then it can respond better and faster. The next time, and then it can respond even better and faster the next time. So every time you're exposed to an infection of the exact same type, so let's suppose you get infected with SARS-CoV-2, for example, and then you get reinfected with SARS-CoV-2, that first exposure, your immune system will remember that. And so it will be better primed to respond to the next infection. So what we're trying to do with a vaccine is sort of mimic that response, get that memory, Going without actually having to make someone infected, because that's not the best solution for most infections, is not to make you infected, it's to sort of trick the immune system into thinking you are. And so one of the ways we can trick the immune system into thinking that is we add this component called an adjuvant. And this really just sort of gives the immune system a little bit of a boost to think, oh, that's something I want to pay attention to, and I want to remember, and therefore that's what I'm going to do. Does that answer the question?

Yes, if only I had an adjuvant for all my immunology classes that I took so many years ago.

Yes, it doesn't boost that kind of memory, unfortunately.

Dang it. Oh, okay. Well, all right. So, Lisa, to you, tell us about the current project of Tvant and what you guys are working on and really the origins and where you guys are today.

So we are working on an adjuvant at Tulane called Tvant. That was developed in the laboratories of James McLaughlin and myself. And this particular adjuvant is based on what we call bacterial outer membrane vesicles. And outer membrane vesicles are basically just very tiny particles, nanoparticles, that are shed from the surface of a bacterium, and they contain numerous signals that our immune system recognizes as foreign. So James just explained how an adjuvant works. The concept of using outer membrane vesicles was basically our way of utilizing something from the bacterium that could trigger an immune response without actually having to deliver the entire bacterium to someone's body. And so we initially started working with outer membrane vesicles as a vaccine platform. We were particularly interested in developing vaccines for biodefense purposes. And we were hoping to develop what are known as non-replicating or non-living vaccines that could be administered to young, healthy individuals, for example, military service members, that would allow them to go into the field and perform their duties without any sort of reactogenicity, meaning no soreness in the arm, no redness, no fever. And so if we were to inject an entire bacterium or an entire virus, which is how some of our older vaccine technologies were derived, you would expect those typical side effects from those types of vaccines. And so outer membrane vesicles are— they are potent in their own way, but they don't cause the types of side effects that you see with whole live organisms. And in many years of study of these outer membrane vesicles, James and I were able to understand how they work as a vaccine to provide really great protection against some of these biodefense organisms. And then we were able to use those and harness those as adjuvants with other vaccine antigens. So in other words, combining the outer membrane vesicle that we've now called Tvant with another vaccine antigen to deliver that vaccine antigen and have the body respond to it in a protective manner. And so we're working on a number of projects right now. Using Tvant, for example, to improve the acellular pertussis vaccine, to try and improve vaccines against salmonella, chlamydia, SARS-CoV-2, and Lyme disease.

So Lisa, you mentioned this is outer membrane vesicles. Something that we've discussed on multiple occasions is that outer membrane vesicles, or OMVs, have been utilized in the industry before. Can you talk a little bit about that?

Yes, absolutely. I think, you know, the first OMV-based vaccine was developed for Neisseria meningitidis serogroup B, which is the causative organism of meningitis. And the OMV platform itself, the one for Neisseria meningitidis, is developed in a— or produced in a different way than Tvant. And we have actually sort of developed the process for producing Tvant at a high yield in a very pure way, in a way that the bacteria make the vesicles for us. Although there are OMV-based vaccines that are out there, the way we derive Tvant is slightly different. And so we've had to partner with manufacturing companies to develop the processes and to establish, you know, the process development for the manufacture of the adjuvant. There are also other companies that are utilizing OMVs as delivery systems Adjuvants and other vaccine technologies. However, from what I've seen, most of those technologies that are OMV-based typically require conjugation or tethering of the antigens to the OMV in order for the platform to be effective. One of the advantages that we have with our, what we call naturally derived outer membrane vesicles or TVant, is that we can simply add mixed TVant with anything, a peptide, a protein, a whole organism, and simply by admixing the 2 together, we can stimulate an immune response to the vaccine antigens. And so that's a very powerful way to utilize this adjuvant because it doesn't require any sort of chemical conjugation or complex steps in order to link the vaccine antigens. We simply admix and inject, and we get an immune response to the vaccine.

That's great. So it's easy to make, you're able to do simpler mixing versus having to actually conjugate, and you can work across a number of different antigens. What are some additional ways that Tvant is better than currently available adjuvants? And either of you can answer this.

I will take that one. I think, as I'd mentioned earlier, if you remember that whole idea about immune memory, so there are 2 parts of that. There are T cells and there are B cells. And so B cells make what we typically think of as the robust anti- or vaccine-mediated immunity that everyone thinks about called antibodies. So these are things that sort of stick to viruses and bacteria and prevent them from being really infectious or dangerous. And then T cells actually serve some other functions, and they can either help B cells be better antibody makers, or they can help other cells be better at what they do, or they can directly kill infected cells, particularly virally infected cells. And so those 2 arms of the immune response, the T cells and the B cells, are not always engaged with current vaccines or vaccine adjuvants. So the most commonly used adjuvant in the world and has been used for over 100 years is called alum. Which is an aluminum hydroxide salt. And it works really well to make a lot of antibodies, but it is pretty bad at inducing a T-cell response. And so for something that requires a T-cell and a B-cell response, which it's turning out is probably almost every infection, we think that Tivant is really good at driving all those. And we have multiple studies now that are showing that that's true, that we can get a really great antibody and B-cell response, and we can get really great—

T-cell response.

Arms of the T-cell response that can become really helpful at making better antibodies or really helpful at killing virally infected cells. And so we feel like this is one of the major reasons that Tivant is so good, is that it can really just sort of engage every part of the immune system that's important for preventing infections. And every time we give it, we give it once and we give it again, we just get better and better antibodies and T-cells over the course of That kind of vaccination route. So most vaccines are given intramuscularly, right? So if you go to the doctor and somebody gives you a shot in your arm with a vaccine, flu vaccine or something, that's almost always into your muscle in your arm, right? And so that's the very, very typical way of giving a vaccine. That's because alum, this other adjuvant, really doesn't work particularly well by most other routes. It's really good in the muscle, but it's pretty terrible at everything else. But if you think about where you get infected, take a breath, you get infected in your lungs. You eat something, you get infected in your gastrointestinal tract. There are other mucosal routes. Female reproductive tract is particularly important for sexually transmitted infections. All of those surfaces we think of are sort of outside the body and they are receiving infections all the time. And so one of the things that we have really thought about and focused on in our group Lisa and I is trying to get the immune response that you want to the place where it's most effective. And the place where it's most effective is really the lungs, the gastrointestinal tract, and the reproductive tract. Where you need those things to happen is where we want to induce an immune response. And one of the things that's great about Tivan is you can give it intramuscularly and it works really well. You can give it intradermally, so you can give it in the skin and it works really well. But you can also give it at sites like the nose where it can prevent an infection that might infect your nose or your lungs, Or you can take it orally. You can basically take it like a pill and it will protect your gut. I'm not going to go further than that because I think that's where I'm going to stop on that. Because there are other ways you could do that, but I'm not sure anyone would take that one. So that's it. Does that answer most of the questions?

No, that's great. So what I'm hearing, so that antibodies are only half the battle as it relates to vaccines, and that just like real estate, location, location, location, that can be really important to to help combat the infection at the site of infection. And that tells me that your, your technology, Tvant, can help make current vaccines, make them stronger, last longer, maybe use less antigen in the process, and making vaccines safer and potentially less expensive, being able to reduce that amount of antigen that's actually required, which sounds like a pretty good value proposition. So Let's dive into what your latest studies of T-Vant have shown you, because you guys have some newer data that I think is really exciting.

So, Elaine, in terms of some of the more recent studies that we have regarding T-Vant, we have some very exciting data with SARS-CoV-2 vaccines. As we all know, you know, the SARS-CoV-2 pandemic, although it, you know, it seems to be, you know, receding somewhat due to both vaccine-mediated immunity and natural immunity across the globe, I think it's pretty evident that although these vaccines that were rolled out and really saved lives from this virus, as the virus continued to mutate, we were made aware that the vaccines were not able to eliminate viral colonization in the upper respiratory tract, in the nose primarily, the nasopharynx as we like to call it. And as a result, the virus continues to transmit across the globe from person to person. And so there's a real effort to design vaccines that can establish good immunity in the upper respiratory tract. And so a disease like SARS-CoV-2, if we could improve through the use of an adjuvant, for example, like Tvant, better immune responses, both antibodies, B cells, and T cells in the upper respiratory tract, we may be able to eliminate the virus from circulation. And so one of the things that we're doing here at Tulane is we're using Tvant intranasally as an adjuvant to adjuvant the spike protein from SARS-CoV-2 to see if we can improve the immune responses in the nose of animals. Now, we're not in clinical trials yet, but in animal studies, if we can improve the immune responses in the upper respiratory tract, and does that translate then to elimination of the virus from colonization or replication in the upper respiratory tract? So those studies are underway and the immune response data looks great. And the challenge studies are pending. We will have that data in a few weeks. But one of the reasons that we're hopeful about that possibility of protecting against SARS-CoV-2 is we have some recent data through a collaboration with Todd Merkle at the FDA, where we adjuvanted the acellular pertussis vaccine with Tvant. And we gave that formulation either intranasally or intramuscularly to infant baboons. So Dr. Todd Merkle at the FDA has shown that the infant baboon is an excellent model of basically pediatric pertussis. And so the baboons can develop disease. They develop the whoop, as it's known, that whooping cough, and they can transmit the bacterium from one baboon to another. So we just talked about SARS-CoV-2, a virus that's still spreading. Well, Bordetella pertussis is a bacterium. That still spreads across the globe, and that is because the acellular pertussis vaccine does not appear to eliminate carriage of the organism in vaccinated individuals. And so people who aren't vaccinated, such as young infants, can still come down with the disease and can die of the disease. And so what we did in this study is tested whether Tvant could improve the immune response to the vaccine and possibly eliminate carriage of the bacterium in the upper respiratory tract or the nose of these baboons. And we just got our results and the data looks fantastic. The intramuscular and intranasal administrations of Tivant with acellular pertussis were both able to clear the organism from the upper respiratory tract of the baboons and protected them from disease and appeared to do so better than the acellular pertussis vaccine on its own, and possibly even better than the whole-cell pertussis vaccine. So this is really, really exciting data, and we're hoping that we can advance these studies further and show people the true potential of something like Tivant and also the power of perhaps intranasal immunization.

That's fantastic. I mean, I think what people don't really quite understand is that sterilizing immunity or preventing the actual transmission of diseases is really unique and very hard to achieve for most vaccines. Most vaccines are excellent at preventing death and preventing very severe and serious disease, but most don't necessarily prevent the actual transmission of the disease. And as we see with whooping cough, it can be so incredibly detrimental, especially to kids that haven't— aren't able to get the vaccine yet. And so being able to achieve elimination of a pathogen before, you know, it gets transmitted, that's really powerful in terms of new vaccine technology. So that's really exciting. Congrats on that data. That's incredible.

Thank you.

Well, that kind of leads me to the next step of, you know, talking about collaborations. Both of you have participated in some partnering meetings with our office. What did you— what did you like about it? What did you hate about it? What surprised you the most? Because these partnering meetings are this intersection of science and industry and business and finding ways to take what you guys are doing From Tulane University and get it into the hands of people that need it? So what did you guys think? I'll start, Lisa, with you and then James.

Yeah, it's a great question, you know, because James and I are true academics and we've been brought up through academia. We've been in academia our whole life and we don't typically think about transforming our inventions in the laboratory into, you know, something that can be used in the clinic or, you know, in the public realm to save lives. And so as you experience success with something that you've developed, you sort of run into that, right? That you have to, you have to move forward, you have to keep going. And how do you do that? And so I think, you know, through the business development office, we've been able to identify good partners. In particular, we've had some really great help and success with finding manufacturing partners. So folks like Catalent and now Scorpius Biologics, who have worked with us to, you know, basically develop these processes for the adjuvant production and, you know, demonstrate reproducibility and consistency from batch to batch. They've also, you know, helped us identify potential groups that can license the technology because as academics, we can only take it so far. We're going to need people to move the technology into clinical trials and hopefully eventual licensure. So yeah, it's been a real learning curve for us, but it's fun.

Great. James?

I don't know that I have a huge amount to add. I really agree with Lisa on the fact that, and I wish this was not true, but that as academics, we tend to really get pushed into not thinking about the things that we study and love and want to understand, as potentially having marketable value, because that's not academic, right? That's not a thing that you think about, because that's not really true learning. But I would disagree with that. And I think, hopefully, this is shifting in academia to start to maybe, thanks to you, your office, to maybe start thinking about, okay, it's okay and wonderful to understand how these things work. And it's okay and wonderful to pursue this just for the knowledge of it. But there's no reason that we can't parlay that into helping Tulane and ourselves and also human health. I mean, I think all of those things can be part and parcel of the same pursuit. And I would love to kind of get a lot of academics out of this mindset of academic pursuit for the love of pursuit only. But that's, maybe that's a different podcast discussion.

Well, as scientists, even in industry, the goal is I love that. I love that. I think that's the perpetuation of knowledge, right? So, and taking what you guys do and moving it into and down the road and making it a product is another form of that. So I love that. All right. So Lisa, where do you think the vaccine industry is headed in general?

I think there's been a lot of interest in media coverage of the messenger RNA vaccines. And so I think, you know, if you were to ask the general, you know, lay public individual, you know, what's the future of vaccinology, they might say messenger RNA vaccines. And I certainly think that those have proved their worth in a pandemic. You know, these were meant to be what we call plug-and-play vaccine technologies. So technologies that you can rapidly adapt to some type of emerging threat, like a pandemic virus. And they've certainly proved their worth in that application. I'm not, you know, convinced that messenger RNA vaccines are going to be, I think that's a great question. I don't think that vaccines are going to be the solution to all infectious diseases or even, you know, necessarily cancer vaccines, although they're certainly being applied to preventing cancer and treating cancer. I think we're going to see a lot of movement towards safer vaccines, particularly with, you know, the vaccine hesitancy and vaccine misinformation that we're experiencing now as a society. You know, trying to develop a vaccine and market a vaccine is going to be tasked with convincing the public that it's safe and effective. And, you know, so it's on us, it's our responsibility to demonstrate that and to be transparent and to show that vaccines are some of the safest inventions that, you know, we've ever introduced into the human body. And that, you know, side effects are expected with anything, any drug, Any biologic, any implant, any medical intervention whatsoever, and vaccines are no different. But we have the power, we have the ability to make safer, longer-lasting vaccines. And we, and we just need to educate the public about the vaccine technology so that they are accepted and they are embraced.

Fantastic. Goes back to being a scientist of how do you move knowledge forward? And that means to How do you get this to the public and show them that not only could it potentially save lives, but it's also safe? Okay, last question. Is there anything that I haven't asked you that you want people to know?

So I don't know that I would say yes necessarily, but I want to build a little bit on what Lisa said. And I think it's incumbent upon us as scientists to be probably better communicators about all of the things that Lisa mentioned, the efficacy of vaccines, how good they are at what they do, how they have basically, in some cases, eradicated horrible diseases from the face of the earth, and also to be honest about the things that might happen if you take a vaccine and you get sick, and that happens. And I think Sometimes we try to, maybe not try to, but we aren't as transparent about that as we should be. And I also would add, I think, and I talk about this a lot with medical students and graduate students when I teach them, is that I think we're something of a victim of our own success in a lot of ways. And that circles back around to the beginning of when Lisa said, we haven't had to experience things like smallpox or polio, but my dad had polio, right? It did some damage to the nerves in his leg, and he still has sort of the side effects from that. We are so good at what we've done with vaccines that nobody really, parents particularly today, have never seen some of these diseases, and they are devastating diseases. And not that I would ever wish upon anyone to have polio or smallpox or diphtheria, but I feel like— We're so good at what we've done that people haven't had to experience how bad that can be in comparison to the rare side effects that come with vaccines. I would like to sort of find a way to navigate that with folks who are uncomfortable with it. And I think that's the last thing I'll leave with.

Yeah, we can be victims of our own success, and it's important to continue educating and important to continue the research and finding ways to make vaccine safer and effective and longer lasting, and that's where you guys come in and brings us full circle of the advantages of Tvent and the work that you guys are doing at Tulane School of Medicine. So guys, thank you so much. We, we look forward to hearing more about Tvent in the future. I look forward to receiving it one day intranasally. Hopefully that would be great.

Me too.

No more having to go to the doctor to get a shot. It'd be nice to have an intranasal vaccine. Well, We have Lisa and James's contact information and some relevant links posted in our show notes. Make sure you check them out to learn more about their research into the T-bone adjuvant.

Thank you.

Thanks, Elaine.

Thanks for joining us for Bio from the Bayou, and we hope you'll join us again. If you'd like to learn more about the emerging biotech scene in New Orleans and the Gulf Coast region, Visit us at biofromthebayou.com, where we have more info on who we are, biotech in the Gulf South, and the industry events we'll be attending where you can meet with us in person. And we'd be remiss if we didn't give a special thanks to the Accelerator Network for providing funding for this podcast. Learn more about them on our website in the show notes. We'll catch you on our next episode of Bio from the Bayou.