Talking Bioech Podcast 442 w/ Dr. Kevin Folta- Measuring the Health of T-Cells - Dr. Nigel McCracken

Hi everybody, and welcome to this week's Talking Biotech podcast by Collabora. Now, those of you who followed the podcast for the last 9+ years know that there are 2 places where I don't usually go very well, and that's brains and immune systems. And so I always like to have guests on who can help me understand these better and better define some of the cool new therapies or diagnostic kits or, or other new remedies that are sitting at the edge of new developments. And so I was very excited to be able to talk to our guest today. So our guest today is Dr. Nigel McCracken. He's the Chief Operating Officer of Virex Biolabs. So welcome to the podcast, Dr. McCracken.

Thank you very much, Kevin. It's nice to be here and it's nice to speak with your viewers.

Yeah, thank you. It's really nice to have you aboard because I was poking around on the website a little bit to learn more about this technology, especially as it applies to issues like long COVID, which we've spoken about a lot on the podcast, especially about its effects that may be exciting other complications. So detection is super important. And so let's start kind of at the beginning. Could you give us a little bit of background, or mostly give me a little bit of background in what the immune system is? So I know we have the humoral immunity, and then is that the funny one?

Yeah.

The humoral immunity.

Yeah, exactly.

Versus innate immune systems, and what are their components?

Yeah, sure. I mean, I think when we're ever exposed to, say, a pathogen, something external and stuff like that, generally what happens is the innate immune system is a very general part of your immune system, and it usually sort of targets— so when we talk about the innate system, we're talking about things like neutrophils and macrophages and white cells and stuff and things like that. But what they do is they digest— they have a general response to the actual pathogen to remove that sort of thing. And again, they release cytokines and chemokines, and we'll talk about these later on, but really just to try and get rid of that in a general sort of way. And in doing so, and we'll talk a little bit about inflammation, you actually do, inflammation's not a bad thing to get rid of viruses. So that's exactly what it specifically do. It triggers the body's innate immune system to get rid of the virus. And then We talk about the adaptive immune system. If your body can't clear it, then it most probably needs more of a precise, you know, targeting of that. And then what happens then? The adaptive immune system provides this more targeted effect where it creates, you know, antibodies. The B cells create antibodies, and then the T cells, the cytotoxic killer cells, actually go and kill the virus. Okay.

That helps a lot because one of the things I saw on your website was a reference of something called T-cell exhaustion. And so what is T-cell exhaustion and how does that play a role in illness or in response to a pathogen?

I mean, it's interesting because I've known about T-cell exhaustion from an oncological point of view. So most of the immuno-oncology drugs treat something like PD-1 or live 3-digit. And these are exhaustion markers, whatever, you know. And what happens, certainly oncology, what happens with T-cell exhaustion, you get a, they call it a cold tumor, an immunosuppressed tumor, whatever, you know. So there's no antigen-presenting cells. So there's nothing for the T-cells to kill the actual cancer. Now, from a virus point of view, it's a similar sort of thing in that if you get chronic antigen stimulation, then basically what happens is your Your T cells start to not function as well as they actually should do. So they don't release the appropriate chemokines or cytokines to specifically fight the infection. And that's what we're talking about, that T cell dysfunction or that T cell exhaustion, and where your adaptive immune system is not efficiently working properly because it can remove the virus without potentially hurting some of your own organs. And if you, you talked about SARS-CoV, if you remember with the SARS-CoV, with, you know, people who were very, very ill, they had these cytokine storms, and that's basically where the immune system was just overactive and it was affecting organs. And that's what's in trying to avoid to do that, and you get that T-cell exhaustion, and in doing so, that dysfunction causes other problems.

Is there a component of this that has to do with aging? As you know, T cells were only called T cells because they originated from the thymus, which kind of disappears as we age. So does that also play a role in the exhaustion process?

To a certain extent. I mean, when you're talking about something like T cell depletion, so you're right, if you've got less T cells or if your T cells that you have aren't functioning properly, they're just less effective at actually removing the virus. And the thing about You talked about long COVID and we'll maybe go on to that a little bit. It's not necessarily just the SARS-CoV. If the T cells aren't functioning properly, some of your latent viruses or viruses that we're all exposed to like herpes or CMV or EBV, they come back up to the front. So it's not just SARS-CoV that's causing the problem. It can be a melee of different viruses which actually come back up from some sort of dormant tissue that they've been lagging in for the Yeah, that's really interesting.

I had a CMV infection come back last November, put me in the hospital, and they had a team of infectious disease specialists who couldn't figure out what was wrong with me. And so they still don't know. I mean, it was— or whether it was cause or effect. So I may be looking for one of your products again someday if it happens again. What is the major mission that your company set out to solve?

Well, what we're wanting to do is we're basically wanting to have a portfolio of T-cell diagnostics and immune profiling solutions in that we want to be able to look at the adaptive immune system. We want to be able to assess a person's adaptive immune status, but also we want to evaluate their protective immunity. The interesting thing around the adaptive immune system is you have these memory T-cells. They remember the infection. And usually when you're then exposed to that infection again, you know, they go straight for it and they attack it sort of thing or whatever. So in relation to, there's almost 2 parts to it sort of thing. When we think about the adaptive immune status, and we've been talking about this T-cell exhaustion or T-cell dysfunction, when we think about something like long COVID, which is a post-viral syndrome sort of thing or whatever, you know, or a post-viral infection. And we also know people maybe who have got ME or chronic fatigue syndrome or even people people have been exposed to something like Lyme disease for a long period of time, they have symptoms that are very similar, like chronic fatigue. They also have some cognitive sort of things which are actually very related to either dysfunction of the adaptive immune system, in particular T cells, but also chronic inflammation. And we'll go into this a little bit sort of later on. Inflammation is a good thing when you're trying to fight an infection. Because you need to create that environment which is hostile either to a bacterial infection or a viral infection. But you certainly don't want that thing to be chronic. And we know about chronic inflammation is not a good thing. And we also know about things like rheumatoid arthritis, which is this autoimmunity where the body is actually attacking itself. So it's trying to actually have tests that give guidance, you know, to individuals. Either around their own protective immunity to specific viruses if they get exposed again, or specifically looking at their adaptive immune system and seeing, you know, if it's in a specific way or if it's dysfunctional. And if it is dysfunctional, can you detect it early enough to have some sort of intervention? That intervention or that management, it may well be a lifestyle, might be a diet, but there may also be some therapeutic that's getting actually, you know, developed specifically for that. Okay.

So this makes a lot more sense to me. So this is essentially a product line that really does a diagnostic assessment of the status of T-cells, whether they're too high or too low, and whether that could be underlying either the presence of a potential problem or maybe your ability to combat disease going forward. Is that kind of in the ballpark?

Yes. So if you think about the evaluation of your protective immunity, and ultimately everybody's been exposed to SARS-CoV, and we will get exposed to SARS-CoV in the future. It doesn't seem to be as much of a problem as it was, but there are certain people in the population, you know, who are immune compromised. So you talked about CMD and SARS-CoV or anything like that. If you're immune compromised and your immune system is not working properly, something like a reinfection of a SARS-CoV or a CMV-related, it can cause problems. And if you know your immune status to certain viruses, then you will know if you've got a memory T-cell response specifically to that. And that will be helpful to give you sort of guidance around, are you at greater risk? Now, specifically in relation to measuring something like T-cell dysfunction, is there the possibility when you think about a post-viral syndrome, and we know it's a huge burden, to society. We know that there's almost 60 million, maybe 60 million-plus people who have got symptoms associated with long COVID. And there are other post-viral syndromes that have similar sort of symptoms specifically. But that chronic inflammation is a real burden to society in that people can't work, some of them can't get up out of bed and whatever, you know. And the question is, can you detect that dysfunction early and then have an intervention prior to getting it to a stage where it's a lot harder to come back from.

No, that's really helpful. We have been talking a lot about inflammation, and I know that when I read things online, I sometimes see inflammation or claims about inflammation that do kind of seem a little dubious. And so, you're having all these problems because of inflammation, and it's used by folks in alternative medicine all the time. Sure. So, can you give me a really clear idea of what does inflammation mean? Like, what's actually happening physiologically that underlies inflammation from a molecular physiological perspective?

I mean, when we talk about inflammation in general, I mean, we're all exposed to it. Yeah, I played a lot of sports. So, usually when you get a bang there, you're going to get some inflammation, you'll get swelling, whatever, because your body's repairing. Or, I'll give If you cut yourself, it's the same sort of thing. If you get a cold, it's the same. So these, inflammation is not necessarily a bad thing. But when we talk about inflammation in particular, when we're talking about, you know, what we're trying to measure, it's more around oxidative stress. And now oxidative stress, again, usually we know about it in oncology. We also know about it from a viral point of view in that when you are exposed to something, your body, you want to create an environment which is toxic and which is not good. not great for the virus or even for, say, cancer specifically. So, you get oxidative stress. Now, oxidative stress is a ratio of reactive oxygen species that people know about because they're the things that age us and antioxidants, and it's just a ratio of that. So, when I'm talking about chronic inflammation or inflammation in relation to post-viral syndromes, I'm talking more about that oxidative stress in that when When you've got that environment which is hostile and it is more chronic, it's going to cause problems specifically to you. And it can damage organs. It can, you know, it can, and again, it can deplete your T cells and it can also have an effect on your mitochondrial dysfunction. And generally the mitochondria in the body is basically 95% of the energy source. So you can start to think about linking certain things to symptoms like chronic fatigue. And again, as well as that, you know, that chronic inflammation, and I know that long COVID has been linked to things like cognitive as well, you can think inflammation in the brain, you could make it, blood vessels have been associated with that. It's generally not a good thing to have chronic inflammation, or at least to be able to understand, you know, why you have that. So you do hear about a lot about. You can change your diet, you can do your lifestyle, and you can generally try and, you know, affect it without having any specific, uh, you know, therapeutic intervention by itself. You know, we hear about anti-inflammatories like nonsteroidal anti-inflammatories. You know, of course we can take these sort of things and whatever, you know, but again, it's just this general chronic inflammation. And we'll go back to that burden thing. What I can see, certainly in the US and certainly where we are based in the The incidences of people who have chronic inflammation is getting higher and higher, and that will cause a burden on society because we know what these things can cause, sort of thing. And although we hear about long COVID now, there's been lots of things like chronic fatigue and ME which have been about for many, many years. And, you know, and the symptoms are very, very similar.

Yeah. When you mention inflammation, especially with respect to the molecular markers that are associated with it, I see your product line has a sensitivity or a way to detect TNF-alpha, which has been associated in some ways with inflammation, especially related to brain neurological disorders including Alzheimer's, things like that, at least in association, maybe causal, maybe not. I don't know what the status of that is. Well, what is the product line for TNF-alpha, the product you have for TNF-alpha, and why is that significant?

Yeah, no, I mean, TNF-alpha is one of these pro-inflammatory cytokines. And, you have other ones like interferon gamma, interleukin-2. So, there's lots of different cytokines that you can measure. So, if you look at our product line, there's different combinations that you can look at. And so, something like we talked about the, you know, when you're looking at your protective immunity or your memory T cell, most people usually look at interferon gamma because it's a good marker to give you some guidance around that, you know, that memory T cell response that you've got an immune response, you know, to a specific virus. So again, TNF-alpha by itself is just a cytokine, a pro-inflammatory cytokine that you usually measure. Now, go back to something like long COVID and T-cell exhaustion in particular. If you look at a lot of papers and stuff, they say that T-cell exhaustion, you tend to, you see reduced interferon gamma, TNF-alpha, IL-2 sort of thing. So, as we develop a test specifically for something like long COVID or a post-viral syndrome, although we are, yes, TNF-alpha is one of the cytokines that we would look at, but when we think about that phenotypic signature that is associated with symptoms of, say, chronic fatigue or cognitive, brain cognitive symptoms associated with long COVID, it will be a combination of different cytokines that we will look at and whatever, you know. So it may not just be TNF-alpha, it might be a combination of TNF-alpha and something else sort of thing.

And is there a diagnostic quality to that? Like if you could see specific ratios of different cytokines, does that help provide guidance into the type of disorder that you may be chasing?

Yeah, no, exactly. When you're actually developing a diagnostic and whatever, you know, obviously there needs to be some sort of utility at the end of it because again, it has to have some sort of value or some predictive value or some sort of help for the individual or, you know, or for the GP who's actually trying to help them. So our thought with respect to something like long COVID, you will put together a a ratio of different cytokines with maybe different cutoffs, which will be linked to some sort of approved questionnaire associated with, say, chronic fatigue or something cognitive like brain fog or something like that, where there's an approved scoring system. And you will link that signature to that. So you've got some sort of prediction of if I measure these specific cytokines with a specific ratio, it will predict symptoms associated with chronic fatigue and brain fog, which are more related to the dysfunction. Now, if you know anything about long COVID, there's lots of symptoms associated with it. I think there's over 200. We're not trying to go for 200 symptoms. What we are trying to develop are T-cell diagnostics and look at the T-cell dysfunction and the actual symptoms that are associated with that T-cell dysfunction.

Oh, very good. Well, we're speaking with Dr. Nigel McCracken. He's the Chief Operating Officer of Virax Biolabs. This is the Talking Biotech Podcast by Collabora, and we'll be back in just a moment. And then we— now we're back on the Talking Biotech Podcast. We're speaking with Dr. Nigel McCracken. He's the Chief Operating Officer of Virax Biolabs, and we're talking about the ways that new technologies can be used to assess the status of various types of T-cells and other cytokines. that can be potentially diagnostic of disorders, inflammation, but may also have some other predictive value. So let's talk about T-cells. I know that in the lab—

Yeah, good idea.

In the podcast here, we've spoken a lot about CAR T-cell therapy over the years, but we already talked a little bit about T-cells and how they're related to immune response. But let's go a layer deeper. What do they actually do inside the body?

I mean, what I was saying to you before, I mean, the T cells themselves, you know, I mean, they're there to kill specific viruses in a very specific way. And when we talk about T cells, you know, they, as I say, they play a role at killing infected cells or helping other immune cells to perform their functions more effectively. And when we talk about T cells, You know, we have helper T cells, and we also have cytotoxic T cells, or CD8-positive T cells, and we have regulatory T cells and memory T cells. But again, what the T cells do is they pretty much get rid of the virus in a very specific manner. And then we also mentioned, you know, once they've specifically done that, they have this memory specifically that they remember the virus. So if you get exposed to it again, it's a very quick response. And we talked about regulatory T cells and also, and we also, we're also aware, certainly in the long COVID, we talked about this whole cytokine storm thing with the regulatory T cells, that there's that regulatory part that actually keeps it in check, that it doesn't go too far sort of thing. So it releases cytokines that are actually, you know, that reduce the inflammatory, like something like IL-10 and stuff and things like that. So there specific different types of T cells. We talked about the helper cells, and again, the helper cells are there to, you know, to bring the right chemokines and cytokines specifically to the party to kill the virus. So yes, it's fairly complicated, but I go back to what I was saying to you before. If the innate immune system can't deal with the problem, i.e., the pathogen, then the adaptive immune system comes in. We have the B cells and the T cells. The B cells will create the antibodies and the antigens And then the T-cells will specifically kill the virus in particular.

Well, it seems to me, so we talk a lot about CAR T-cell therapy on the podcast. We've had a number of guests on regarding this technology. And what we've seen over the last maybe 5, 6, 7 years of talking about it is that it isn't as cut and dry as we thought, that there are many caveats that have to be considered. within a patient's response or potential lack of response to this kind of therapeutic, some which can be dangerous. So how can your technologies really guide physicians potentially in administering a CAR T-cell therapy?

Well, that's a great point, Kevin. As you know, CAR T-cell therapies, and certainly in oncology and hematological oncology, has been about for a number of years. And specifically, it is quite expensive because it was specifically related to the person's T-cells where you would take T-cells out that you'd manufacture and then put them back in. I think nowadays, you know, to try and keep those costs down, people are moving to more that allogeneic type of off-the-shelf, you know, where you have T-cells that people can use. So when— To your point, the question is, is if you have some T-cell diagnostic, could you help either identify patients who would benefit most? Because T-cell, CAR T-cell therapy doesn't benefit everyone. So the question is, could you determine that? And what if, you know, if you're looking at somebody's T-cells or their immune system or whatever in the general, could you actually help with that? And then when you think about dosing, the dosing of those, that CAR T-cell therapy, as you mentioned before, you've got to get this, the number of T-cells right. And whatever, you know, because if you go too far, you cause potential problems. And we've heard about certainly some cytokine storms specifically related to, you know, certainly stroke patients. Or if you go too low, you're not going to get the full effect. So the thought here is, you know, could we actually partner and help specifically with that and whatever, you know? And that's certainly, that's something that we would like to think about. And it's It is something that obviously, you know, pharma companies specifically are doing because it doesn't help everyone and it is very costly. However, it is very effective in certain people and it's been quite revolutionary. And our thought is that certainly with, if you can look at the T-cells and look at their functionality and their, could you actually help with To be more precise and more helpful specifically around that CAR T-cell therapy.

And then just going back to more regular familiar disorders that we recognize, your product line seems to target quite a few of them. And it's a really diverse product line. Some of the things I don't even recognize, but something like, let's say herpes, is this something that you would use to be able to detect if somebody perhaps had a latent infection and wasn't presenting where you would be able to detect it with either, you know, physical markers of a herpes infection or PCR or something like that? Is it really to detect that the body has seen the virus?

So we mentioned that most of us have got all of these latent viruses. So herpes is one of the things that, you know, 80% of the population have got, have had herpes. And obviously some people manifest it a little bit more than others with cold sores and stuff and things like that. And we've also talked about things like CMV or EBV, And whatever you— when we talk about those specific viruses, the Virax immune platform, the platform that we specifically have, there are different components to the actual diagnostic test. So we're specifically using peptide mixes for each of the viruses to stimulate the T cells. And then we can actually see the response from that. So when we think about something like herpes or some of those other viruses, and we'll go back to, you know, the whole thing around the post-viral syndrome, or long COVID in particular, the chances are it's not just SARS-CoV by itself that's causing the problem. It's that SARS-CoV, the antigen stimulation, the T cells aren't working. You've got something like herpes, maybe EBV that are starting to come up and overwhelming the actual system. So when you look at our product line, our product line is there to sort of help researchers who are working within that. But when we think about something like a post-viral syndrome, We know that you need to not— something like long COVID, you can't just look about the effect of SARS-CoV. You've got to look at the other viruses as well because the reality is it's most probably a combination. And that's the reason why our product line has got lots of different viruses that we can specifically look at because the reality is it's most probably a combination of all of those that's causing the general problem with a lot of these symptoms that are associated with these post-viral syndromes like long COVID.

And maybe we could touch on really the technology more specifically, if we can discuss, like, how exactly does this work? You mentioned that you're using peptides to stimulate the T-cell response. And then, so can you gimme a little bit more of a sense on how that works?

Yeah, it's a 96-well plate format. We're not using blood and plasma because with blood and plasma, you get lots of cytokines that are in it all the time. So, historically, I think a lot of people have used things like ELISA. And ELISA's great, you can measure lots of different things. But again, depending how you're feeling, if you've got a cold, your cytokines are going to be up there. The nice thing is we're using PBMCs, or, you know, which are You know, peripheral blood mononucleocytes. Now, when you work with PBMCs, you start with zero and then you're activating them. So we are activating them with a SARS-CoV peptide mix, which means the signature that we get from those T cells that are activated is very specific for SARS-CoV or is very specific for herpes. So we would, rather than this general sort of cytokine signature that could be affected by a number of things, you know that it's specifically affected for that virus. Now, within that 96-well plate format, we have the ability, because we're using a technology called FluorSpot, within each well we can have up to 3 cytokines that we specifically look at. And then usually with the 96-well plate format sort of thing, you've got 8 wells and there's 12 actually rows sort of thing. So you've got the ability to look at different combinations of cytokines that are specific to that virus, whatever, you know. So, so there are, there are a lot more, um, specific— the signature is more specific.

And that's—

and now how we would do is we would actually capture that with a fluorescence reader sort of thing. And that— and again, it's a general fluorescence reader. It's not, um, specific, you know, like something like flow cytometry, where, where it's very specific to the actual equipment that you specifically use. The good thing about the Fluorespot and flow cytometry is it gives you an idea about the origin of that signal or that T-cell activation. Is it CD4? Is it CD8? You know, so, and that's super important to understand because we, when we talk about the immune system, whatever, you know, it is complex. And something like long COVID is a very complex sort of disease. And we know that as the, you know, as the months and years go on and we get more and more information out of that, we will start to understand that. Now, going back to where we— and if you look at the product list, you know, with the Virex, I mean, we have the flexibility to move quite quickly. And, you know, and with respect to the technology and the different cytokines as well, sort of thing. So, going back to what we want to do is we want to have this portfolio of T-cell diagnostics and immune profiling solutions that researchers can use. But specifically what we do want to do is to create some in vitro diagnostics to CE market that clinicians can use to help either diagnose the T-cell dysfunction early, to help with the management of somebody who has got something like post-viral syndrome, or to give some sort of guidance on a person, you know, their immune profiling, you know, the basic, I mean, You know, whether they've got immune response to specific viruses. So again, for most people, it might not be that important, but certainly for some people who are more at risk, either immune compromised, you know, diabetic and whatever, it's super important.

Yeah, I think I'm really starting to understand this now. So you're able to use a peptide, like a specific ligand for a specific T-cell receptor, and then that will give you a fluorometric signal that's quantitative that gives you a really good sense as to how Or how robust that particular response is in any given patient at any given time.

It is.

Am I right?

Do I get it? Yes, yes, you're exactly right. Now, when you think about, just to give you, I mean, it's not the fact that the technology hasn't been used before, it has been used before. So when you think about something like, you know, evaluation of predictive immunity, people who are immunocompromised, people who maybe receive, who are getting a transplant, you know that the patient Basically, if you're immune compromised, and usually you'll get, it's super important to look at some viruses. Because again, usually they're vaccinated prior to transplant. And you also need to look at the recipient and the donor to see if they've got any specific viral infections. You mentioned sort of CMV before. CMV's one of these important things. in transplant, kidney transplants, because—

Yeah.

You know, in kidney transplants, because you're immunocompromised, these latent viruses start to come up and cause problems and whatever, you know. And certainly with CMV, it can affect a number of organs and it can be problematic certainly for rejection, you know, a year down the line from, you know, following transplant. So there is the ability to look at something like this for something like transplant, and that has been used before sort of thing. So, and it is used before, and that's certainly something that we will look to pursue as well.

There's been a lot of interest in avian influenza lately here in the States anyway. And so how do your product line— how is your product line used in examining avian influenza response?

So to the point, and as you mentioned, you know, we have certainly within the facility, in the lab, We have specific peptide chemistries, we have specific peptide mixes for the different viruses, including the avian flu. So again, you can look at the avian flu from the point of view of testing for it. And certainly, we have antigen and PCR tests to test specifically for that if need be, but it's more around the immune response as well. So again, do you actually have an immune response specifically to that? Because if you do have a memory T-cell immune response to that, then it would be potentially less problematic sort of thing, whatever, you know, because it's not something completely new sort of thing. So again, at the moment we have the evene influenzae research, you know, and so LDT as we would call it in the US sort of thing, whatever. And certainly they're there for researchers, you know, to specifically use and work with.

Yeah, and so for something like long COVID, I'm imagining that this could be very useful because it wouldn't necessarily be thrown off by new variants, right? You would be able to detect a COVID response that was based upon more of the generic features of the virus. That would— tell me a little bit more about that.

Sure. I mean, when you think about— so the SARS-CoV, let's just use— we're talking about SARS-CoV here. We've basically got I think 2 peptide mixes, an MHC I and MHC II, which deals with both the CD4 and the CD8 parts of that sort of thing. Now, again, because it's specific peptide mix, again, it's very specific to that. It's made up of different epitopes of the specific virus. And again, you will get a response from those T cells from the PBMC. So it's not, as you said, it's not really specific for any specific variant. Now, when we talk about exposure to SARS-CoV, you know, whether that's following vaccination or whether it's, you know, whether it's following exposure of a different variant, we will do, and people will get exposed specifically to that. And again, if you read papers, of course it's not as prevalent as it was, but certainly I guess the potential is, is the more times you're exposed, the greater chance you've most probably got of getting some symptoms that are associated with long COVID. So although when we talk about exposure to SARS-CoV, it's not going to go away. And the question then, going back to the T-cell diagnostic around, is there a way to detect it early? Because what you don't want to do is leave it too late. And the thought is, you know, if you leave it too late, would your immune system hardwire into a new paradigm? And then once it does that, is it harder to come back from sort of thing? And again, you know, So if you look at a lot of papers and they look at certainly some of the major symptoms like chronic fatigue and cognitive brain fog and stuff and things like that, for something like ME, chronic fatigue syndrome, long COVID, or even somebody who's maybe had Lyme disease for a long period, it's very, very similar. And so the question then is, is that dysfunction of the adaptive immune system, particular T cells? have an effect on, you know, and dysfunction of the mitochondria and oxidative stress because they're all very, very linked. They're very linked within the innate immune system as well as the adaptive immune system. And so I, I think, you know, I'd be very surprised if a lot of— there's not an awful lot of commonality, uh, you know, if you leave symptoms long enough, a post-viral And there'll be an awful lot of commonality around a lot of the major symptoms, not all of the symptoms, but a lot of the major symptoms.

Is there a utility for your platform potentially to work in tandem with vaccination strategies that, you know, I've been vaccinated, I've had SARS-CoV-2 infection, but I sure would like to know my state of immunity now to whether I should go get another booster or, you know, or do I have sufficient Sure. You see where I'm going. Do I have sufficient antibodies in me?

Exactly. And to the point, yes, you can. Because usually what you would expect when you have, certainly if we've all been, the majority of us have been vaccinated, and usually what you get a T-cell response. And I think certainly some of the viruses, they're obviously, sorry, a lot of the vaccines are slightly different. based, you know, vector-based and stuff and things like that. But generally, you know, you've got a 6-month, you know, T-cell response, and then it tends to wane off sort of thing. And it's different for some of the different vaccines. So, yes, you could use the test specifically for SARS-CoV to look to see, you know, how your immune response was. And when I mean after a period of time, to see if you needed to get another boost. Now, for most people, that might not be the— they might not specifically want that. But certainly there are populations, you know, that might be immunocompromised, might be at greater risk, where that is super important. So you talked about, you know, when companies are developing vaccines, of course they look at the serology, they look at the antigen formation or the But they don't regularly test for the immune response because the immune response is very important. You can have an antibody, but you can have quite a weak response. So going back to something like the transplant with something like CMV and whatever, of course people will have the virus and whatever, but it's important to know what the immune response, because if you've got a strong immune response, then you may be less of a risk risk, and what if you're somebody who doesn't, sort of thing. And again, going back to what we were talking about with the SARS-CoV, if that person doesn't have a strong memory T-cell response specifically to that, it may well be that they might want to actually get, you know, another booster or another vaccine specifically for that. So we've talked about SARS-CoV. You could say the same thing about RSV or influenza, you know, anything 'Cause there are certain people who are at more risk, elderly, young, and whatever, you know. And certainly, you know, when we talk about developing the diagnostic, you know, we're working with researchers, we're doing clinical studies, you know, those, you know, longitudinally as well, sort of, you know, over a couple of years. We want to also increase the knowledge specifically around this as well as develop the actual diagnostics as well.

Is something like this ever going to be amenable for, say, home use rather than have to have a clinical test?

I think ultimately, ultimately, if you can, you would love to be able to specifically do that. So when you think about your antigen tests and stuff and things like that for SARS-CoV and whatever, would it get to that? No. But I think certainly what we want to be able to do is we want to be able to turn around that, excuse me, that data quickly. And when we talk about quickly, within a few days. So you could even think about, could you provide some sort of app where you could actually sort of get that information back to the person within a few days and stuff like that? Now, ultimately what we want to be doing is we want to be working with the healthcare providers because we want to be sort of helping with that diagnosis to the person quickly, as quickly as we specifically can. And we certainly don't want to be doing things or making sort of decisions for people, which takes away from that clinical intervention, 'cause that's super important. So we want to be working with the investigators and who understand and know whether it be Lyme disease or whether it be long COVID or whatever, you know? And that's super important because it has to have value. And we want to, we'd love to be able to get it right in at the beginning of that journey because Going back to something like ME or chronic fatigue, people, the problem there many, many years, and I've known lots of people who have ME, it's the diagnosis. And the diagnosis, there's no diagnosis for long COVID and there's no diagnosis for ME, or at least no diagnostic for that. And the problem is when it's left too late, it becomes more of a problem.

Yeah, that's a— we've had a number of guests on the podcast series over the years that talk And one of them with respect to SARS-CoV-2 about the potential to excite endogenous human retroviruses if you are maintaining these latent infections. And they do manifest as some severe neurological disorders, things like that. So, I really think these are really cool technologies. And you mentioned Lyme disease.

Yes.

Last November when I had my bout that ended up in the hospital with recurring fevers, the first thing they treated me for was Lyme disease because some of the symptoms overlapped, but they said the test is really lousy. So is this kind of test a real improvement upon standard ways to detect Lyme disease?

Yes. So as you said, there are, I think nowadays, you know, when you're tested for Lyme disease, it's ELISA-based and Western blot-based. I think they're the 2 sort of, and I guess the problem, I mean, I think people who get a tick bite, you know, 40% will get the, you'll get around the round sort of circle, maybe But 70% don't. I guess the problem with the tests at the moment, they're not overly sensitive in that they miss quite a lot of people. And usually what happens is people will go through an antibiotic treatment for say 28 days sort of thing, whatever. So the thought is that it misses a lot of people. And even following the antibiotic treatment, you're just waiting another 3 months to see if any of the focal or non-focal symptoms actually sort of come up with Lyme disease. So what we're wanting to do with respect to, you know, our sort of, you know, diagnostic is to, yes, look at the IgG, IgM antibody production, but also look at the interferon gamma, IL-2, or the immune response as well to that, or whatever, you know. So, and the hope is that that by itself, that you've got an immune response, you've got the antibody, it will give you some sort of idea of when you actually got the infection, but it will also give you some guidance on the immune response. And the question there is, if you go onto the FDA website, I think where they want to go is if they want to have a diagnostic that is more sensitive, but also gives some sort of guidance on the cure or whatever, you know, because again, you go through one set of antibiotics and you don't really know if it's working or not. So the thought here is, is there something that you can do with the test to help with that sensitivity, but also give some sort of guidance with the actual treatment itself. So we will be, and we are sort of working with specific researchers, not just for the people who have had Lyme disease for a number of years and they've got, say, some sort of dysfunction in the nervous system, but also for people who are newly diagnosed and to follow them over that, you know, 6-month, 12-month period and wherever to see if we have a diagnostic that's more sensitive, but also gives a lot of guidance on the immune response specifically to that. And does that actually give you some guidance around the cure, you know, or the treatment of those people, which needs to be a lot better than it actually is.

And I guess maybe kind of winding down here, but Different cancers, and I may be speaking outside of my expertise. It seems like different cancer subtypes have different presentations of surface antigens that excite a T cell response to some degree. And is there a potential diagnostic value to your technology that may be able to see the presence of any kind of neoplasia before it actually manifests as, say, a solid tumor or actually as something that would present? Normal cancer type symptoms.

Yeah, I mean the thing is is most of these you know we talked about you know PD one and LAG three and stuff and things like that. What have you know the hematologically maybe the solid tumors usually you know the solid tumors you need biopsies and stuff and things that's the problem. You know unless it's maybe it's you know it's it's dermal or something like that. That, it's most probably a little bit more amenable sort of thing again. But biopsies, and you're talking to somebody who's worked in oncology for the last 20 years, and it is a complicated business. And that's when we talk about oncology, we talk about the tumor microenvironment. That microenvironment is, I'm going to say, it's very similar. It's very similar to the, it's chemokines, it's cytokines, it's oxidative to stress that, you know, it's, you know, a cancer's slightly different, 'cause what it will do is it will shut off all of the things that are there to kill it, you know, and it will, you know, so I think for us, other than the CAR-T, because it's hematological and we can actually, we can get the, 'cause it's more of a liquid type biopsy, not a lipid biopsy or a liquid sort of diagnostic that we're doing, that might be a little bit more amenable. But with respect to the solid tumor, because you need to actually get into the actual tissue itself and take the tissue, I think, you know, the current sort of sequencing that is done, you know, for specific mutations, you know, by a lot of the sort of companies, that's most probably where it's gonna be, where you're looking at specific mutations. And there's been huge bounds made in the field around understanding specific mutation or driver mutation.

Well, Dr. Nigel McCracken, thank you very much for your time today. This was really exciting. If people want to know more about Virax Biolabs, where do they look?

Yeah, thanks, Kevin. You can find all of our social media links on the pages at the bottom of our website, and the website being viraxbiolabs.com.

That's V-I-R-A-X, right?

V-I-R-A-X. V-I-R-A-X.

Yes.

We do have Twitter X handle accounts at Virax Biolabs, Virax_Biolabs. Yeah.

Very good. Well, thank you very much for joining me today. Best wishes. And as products emerge and applications come out, please get back to me and we'll have you on again.

Okay.

Thank you.

Thank you very much, Kevin.

Thank you again for listening to the Talking Biotech podcast. Think about new novel diagnostic tools and ways that they may be used to help us understand the prevalence of specific disorders. They may help us from things from herpes to understanding long COVID, which could be quite a problem as we've seen. So this is the Talking Biotech podcast by Collabora, and we'll talk to you again next week.