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Talking Biotech is a weekly podcast that uncovers the stories, ideas and research of people at the frontier of biology and engineering.
Each episode explores how science and technology will transform agriculture, protect the environment, and feed 10 billion people by 2050.
Interviews are led by Dr. Kevin Folta, a professor of molecular biology and genomics.
Hi everybody and welcome to this week's talking biotech podcast by Colabra
Now those of you who followed the podcast for the last nine plus years know that there are two 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 was very excited to be able to talk to our guests today. So our guest today is Dr. Nigel McCracken. He's the
Operating Officer of Virax Biolabs. So welcome to the podcast Dr.
Nigel McCracken (02:00.234)
Thank you very much, Kevin. It's nice to be here and it's nice to speak with your peers.
Kevin Folta (02:06.514)
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? The humoral immunity versus innate immune systems and what are their components?
Nigel McCracken (02:41.612)
Yeah, that's what I wanted to hear exactly.
Nigel McCracken (02:50.316)
Yeah, sure, I 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, what they do is they just...
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. in doing so, and we'll talk a little bit about inflammation, you actually do, inflammation is not a bad thing to get rid of viruses. So that's exactly what it's specifically doing. It triggers the body's innate immune system to
rid of the virus. And then when we talk about the adaptive immune system, if your body can't clear it, then it most probably needs more of a precise targeting of that. And then what happens then, the adaptive immune system provides this more targeted effect where it creates antibodies, the B cells create antibodies, and then the T cells, the cytotoxic killer cells actually go and kill the virus.
Kevin Folta (04:17.724)
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?
Nigel McCracken (04:35.574)
I mean, it's interesting because I've known about T cell exhaustion from an oncological point of view. most of the immuno -oncology drugs treat something like PD1 or LAG3 or TIGID. And these are exhaustion markers. whatever you know, what happens, certainly oncology, happens with T cell exhaustion, get, they call it a cold tumour, an immuno -suppressed tumour, wherever you're in it. So there's not antigen presenting cells. So there's nothing for
Kevin Folta (04:45.785)
Nigel McCracken (05:05.46)
T cells to kill the actual cancer. Now, from a virus point of view, it's in a similar sort of thing in that if you get chronic antigen stimulation, then basically what happens is 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
function or that T cell exhaustion and where your adaptive immune system is not efficiently working properly because it can't remove the virus without potentially hurting some of your own organs. And you talked about SARS -CoV, if you remember with the SARS -CoV, people who were very, very early had these cytokine storms and that's basically where the immune system was just overactive and it was affecting organs. And that's what,
trying to avoid to do that and you get that T cell exhaustion and in doing so that dysfunction causes other problems.
Kevin Folta (06:13.536)
Is there a component of this that has to do with aging as, you T cells were 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?
Nigel McCracken (06:20.557)
Yes.
Nigel McCracken (06:25.742)
To a certain extent, mean, you're talking about something, 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 are viruses that were all
Kevin Folta (06:34.338)
okay.
Nigel McCracken (06:55.668)
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 last number of years.
Kevin Folta (07:18.952)
Yeah, that's really interesting. I had a CMV infection come back last November, put me in the hospital. And I had a team of infectious disease specialists who couldn't figure out what was wrong with me. And so they still don't know. mean, or whether it was cause or effect. So I may be looking for one of your products again someday if it happens again. But let's talk about really the problems that your company is setting out to solve with all of that as a background.
Nigel McCracken (07:47.437)
Yep.
Kevin Folta (07:48.158)
What are some of the major products in the product line that, let me say it this way, what are the major way, let me say it one more time, I'll edit this. What is the major mission that your company set out to solve?
Nigel McCracken (08:06.478)
Well, what we're wanting to do is we were basically wanting to have a portfolio of T cell diagnostics and immune profiling solutions. And 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 the protective immunity. The interesting thing around the adaptive immune system is you have these memory T cells. They remember the
And usually when you're then exposed to that infection again, you know, they go straight for and they attack it sort of thing or whatever. in relation to there's almost two 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, know, or a post viral infection. And we also know people maybe who have got ME or chronic fatigue syndrome, or even
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 to individuals, either around their own protective immunity to specific viruses if they get exposed again,
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 can you detect it early enough to have some sort of intervention that 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 getting actually you know developed you know specifically for that.
Kevin Folta (10:35.654)
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?
Nigel McCracken (10:59.006)
Yes, so if you think about the evaluation of your protective
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 who are immune compromised. So you talked about CMV 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 CMV or a latent, 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 symptoms specifically. But that chronic inflammation is a real burden to society in that people can't work, some of can't get up out of bed and one of 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.
Kevin Folta (12:37.49)
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
seem a little dubious. so, you're having all these problems because of inflammation. And it's used by folks in alternative medicine all the time. So, can you give me a really clear idea of what is inflammation mean? What's actually happening physiologically that underlies inflammation from a molecular physiological perspective?
Nigel McCracken (12:58.21)
Yeah. Sure.
Nigel McCracken (13:14.306)
mean when we talk about inflammation in general, mean we're all exposed to it. 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 you, because your body's repairing. If you cut yourself it's the same sort of thing. If you get a cold it's the same sort of Inflammation is not necessarily a bad thing, but when we talk about inflammation, in particular when we're talking about what we're trying to measure, it's more around
Oxidative stress again, usually we know about it in oncology. We also know about it from a viral point of view and that when you're exposed to something, you want to create an environment which is toxic and which is not great for the virus or even for say, know, cancer specifically. you get oxidative stress. Now oxidative stress is just a ratio of reactive oxygen species
people know about because they're the things that age us and whatever you know and antioxidants and whatever you know 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 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, 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. can think inflammation in the brain, you've got leaky blood vessels have been associated with that. It's generally not a good thing to
Nigel McCracken (15:23.68)
chronic inflammation or at least to be able to understand why you have that. So you do hear a lot about you can change your diet, can change your lifestyle, you can generally try and affect it without having any specific therapeutic intervention. By itself, we hear about anti -inflammatories like non -steroidal anti -inflammatory. Of course we can take these sort of things and whatever you know, but again it's just
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 UK, 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
which have been about for many many years and you know and the symptoms are very very similar.
Kevin Folta (16:30.706)
Yeah, there's a, 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 with 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. But what is the product line for TNF -alpha, the product you have for TNF -alpha, and why is that
significant.
Nigel McCracken (17:07.335)
Yeah, no, mean, TNF Alpha is one of these
inflammatory cytokines and you have other ones like interferon gamma, interleukin 2. So there's lots of different cytokines that you can measure. if you look at a product line, there's different combinations that you can look at. So something like we talked about when you're looking at your protective immunity or your memory T cell, most people you usually look at interferon gamma.
it's a good marker to give you some guidance around that memory T cell response that you've got an immune response to a specific virus. again, TNF -alpha by itself is just a cytokine, a pro -inflammatory cytokine that you usually measure. Now, going 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 tend
you see reduced interfering 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, it will be a combination of
different cytokines that we will look at and whatever you know. So it might not just be TNF -alpha, it might be a combination of TNF -alpha and something else sort of thing.
Kevin Folta (18:51.345)
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?
Nigel McCracken (18:59.692)
Yeah, when you... Yeah, no, exactly. When you're
developing a diagnostic and whatever, and 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 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 ratio of different cytokines with maybe different cutoffs, which will be linked to some sort of approved questionnaire
say to a say chronic fatigue or something cognitive like brain fog or something like that, where there's a 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're 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.
Kevin Folta (20:24.922)
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 Colabra. And we'll be back in just a moment. And then we take a little break here on the... Everything okay? Yeah, real nice. I love your answers.
Nigel McCracken (20:40.371)
Yeah, no, great, absolutely great. Yeah, no, you know this is super complicated.
Kevin Folta (20:46.964)
I know it's I'm really getting some clarity into this now that I've been through it a thousand times I have a lot of folks on who talk about CAR T cell therapy and That's been that's been real big on so I'm getting there, but it's I don't know why I have this kind of blind spot to even wanting to get
Nigel McCracken (21:07.342)
When you're thinking something like CAR T cell therapy, the question is, because CAR T cell therapy is going allogenic eye off the shelf, the question is how do you predict...
you know, somebody's going to respond to it. You don't just put the same amount of cells in. So the question is, we were going to move into CAR T just to see, you know, could we look at somebody's T cell immunity, you know, or their T cells to help predict with the actual sort of dosing of that or to give some sort of guidance around that, you know, that cytokine storm, because if you get too many cells, you know, it's going to be too bad. And some people might not actually respond to CAR T cell therapy. So can you
Kevin Folta (21:40.894)
Yeah.
Nigel McCracken (21:48.4)
determine that because it's very expensive it's like 600 ,000 you know you know so again there's lots of things that you can actually take the technology into.
Kevin Folta (21:58.298)
I may ask you about that as we move through here today. We'll watch the time and see where we go. So here we go. here. Okay, let's just go ahead and start back in. Here we
Nigel McCracken (21:59.97)
Okay.
Kevin Folta (22:10.94)
And now we're back on the Talking Biotech podcast. We're speaking with Dr. Nigel McCracken. He's the chief operating officer of Vyrax 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, in the podcast here, we've spoken a lot about CAR T
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 like what what do they actually do inside the body?
Nigel McCracken (22:55.064)
I mean, what I was saying to you before, I the T cells themselves, you know, I mean, they're there to kill specific virus in a very specific way.
And when we talk about T cells, as I say, they play a role in killing infected cells or helping other immune cells to perform their functions more effectively. And when we talk about T cells, we have helper T cells, 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 we also mentioned, 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're also aware, certainly in the long -cove, we talked about this whole cytokine storm thing, but the regulatory T cells, 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 are specific different types of T cells we talked about the helper cells and again the helper cells are there to you know to you know to bring the right chemokines and cytokines specifically to the party to kill the virus so 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 ate 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.
Kevin Folta (24:54.718)
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 five, six, seven 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 of which can be dangerous. So how can your technologies really guide physicians potentially in administering a CAR T -cell therapy?
Nigel McCracken (25:29.006)
That's a great point, Kevin. you know, CAR T -cell therapies and certainly oncology and hematological oncology has been about for a number of years. Specifically, 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, to try and keep those costs down, people are moving to more that allogenic type of off the shelf, where you have T -cells that people can use.
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 is could you determine that and what if you know if you're looking at some of these T cells or their immune system and whatever in the general could you actually help with that and then when you think about dosing the dosing of those that car
cell therapy. As you mentioned before, you've got to get the number of T cells right, because if you go too far you could potential problems and we've heard about certainly some cytokine storms specifically related to certainly some patients. Or if you go too
you're not going to get the full effect. So the thought here is, could we actually partner and help specifically with that and whatever you know. And that's something that we would like to think about. it is something that obviously 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 if you can look at the T cells and look at their functionality and could you actually help to be more precise and more helpful specifically around that CAR T cell therapy.
Kevin Folta (27:34.352)
And 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 physical markers of herpes infection or PCR or something like that? Is it really to detect?
that the body has seen the virus.
Nigel McCracken (28:09.358)
So we mentioned that most of us have got all of these latent viruses. So herpes is one of the things that 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. When we talk about those specific viruses, the Vinax immune platform or the platform that we specifically have,
to the actual diagnostic tests. So we're specifically using peptide mixes for each of the virus to stimulate the T cells. And then we can actually see the response from that. So when we think about some like herpes or some of those other viruses, and we'll go back to 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,
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 at 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.
Kevin Folta (30:03.238)
And maybe we could touch on really the technology more specifically, you know, 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 give me a little bit more of a sense on how that works?
Nigel McCracken (30:21.39)
Yeah, it's a 96 -well plateformer. We're not using blood and plasma because with blood and plasma, you get lots of cytokines that are in it all the time. historically, I think a lot of people have used things like ELISA, and ELISA's great. You can measure lots of different things. 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, which are peripheral blood mononucleosides. Now, when you work with
you start with zero and then you're activating them. So we're 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. we would, we, rather than this, 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 three cytokines that we specifically look at. And then usually with the 96 -well plate format sort of thing, you've got eight wells and there's 12
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 specific the signatures 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 again it's a general fluorescence reader it's not specific you know like something like flow cytometry where
Kevin Folta (31:48.168)
Yeah.
Nigel McCracken (32:10.66)
very specific to the actual equipment that you specifically use. The good thing about the Flurispot and also 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? And that's super important to understand because when we talk about the immune system, it is complex. And something like long COVID is a very complex sort of disease.
We know that as the months and years go on and we get more 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 with the Vyrex immune, we have the flexibility to move quite quickly 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
solutions that researchers can use but specifically what we do want to do is to create some in vitro diagnostics to CE marking 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 a post viral syndrome or to give some sort of guidance on a person you know their immune profiling you know their basic
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, know, or diabetic and whatever, it's super important.
Kevin Folta (33:57.672)
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 much or how robust that particular response is in any given patient at any given time. Am I right? I get it? Okay.
Nigel McCracken (34:16.308)
It is, yes, yes, you're exactly right. when you think about, just to give you, 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, know, evaluation of predictive immunity, people who are immunocompromised, people who maybe receive, who are getting a transplant, you know that basically 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 CMV before. CMV is one of these important things, in transplant and kidney transplants because in kidney transplants, because you're immune compromised,
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 falling transplant. So there is the ability to look at something like this for something like transplant, and it has been used before, sort of thing. And it is used before, and that's something that we will look to pursue as well.
Kevin Folta (35:45.016)
There's been 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?
Nigel McCracken (35:57.098)
So to the point and as you mentioned, know, we have certainly within the the within the facility in the lab, we have specific peptide chemists, we have specific peptide mixes for the different viruses, including the avian flu. So again, you can you can look at the avian flu from the point of view of testing for it. And certainly, you know, we have antigen and PCR tests to test specifically for that need be. But it's more around the immune response as well. So again,
you know, 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 avian flu as research, you know, sorry, 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.
Kevin Folta (36:58.728)
Yeah, and so for something like long COVID is 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.
Nigel McCracken (37:23.074)
Sure, mean, when you think about, so the SARS -CoV, let's just, we're talking about SARS -CoV here. We've basically got, I think, two peptide mixes, the MHC1 and MHC2, which deals with both the CD4 and the CD8 parts of that sort of thing. 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
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, whether that's following vaccination or 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
the potential 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 -2, it's not gonna 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, 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, if you look at a lot of papers and they look at the 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 of time, it's very, very similar.
The question then is, is that dysfunction of the adaptive immune system, particularly T cells, have an effect on...
Nigel McCracken (39:32.588)
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. So I think, you know, I'd be very surprised if a lot of, there's not an awful lot of commonality. You know, if you leave symptoms long enough, a post -viral syndrome, 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.
Kevin Folta (40:01.492)
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, you see where I'm going, do I have sufficient antibodies that would...
Nigel McCracken (40:22.35)
Sure.
Nigel McCracken (40:25.676)
Yeah, no, exactly. And to the point, yes, you can. Because usually what you would expect when you have, certainly the majority of us have been vaccinated. usually what you, you get a T cell response and I think certainly some of viruses, there are obviously, sorry, lot of the vaccinations, vaccines are slightly different. based, vector based and stuff and things like that. But generally, you've got a six month
you know, a T cell response and then it tends to wane off sort of thing and it's different for some of the different vaccines. yes, you could use the test specifically for SARS -CoV to look to see, you know, how your immune response was and whatever, know, after a period of time to see if you needed to get another booster. 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 immune compromised, might be a
to risk where that is super important. So you talked about you know when the
Companies are developing vaccines. Of course, they look at the serology, they look at the antigen formation or the anti... 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, know, of
people will have the virus and what have you know but it's super important to know what the immune response because if you've got a strong immune response then you may be less of a risk and whatever you know there's 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 you know another booster another vaccinated specifically for that. Now we've talked
Nigel McCracken (42:33.284)
SARS -CoV you could say the same thing about RSV or influenza, know anything because 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.
Kevin Folta (43:07.856)
Is something like this ever going to be amenable for say home use rather than have to have a clinical
Nigel McCracken (43:15.286)
I think ultimately, ultimately, if you can, you would love to be able to specifically do that. 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, you know, within a few days, you know, so you could even think about, you know, could you provide some sort of app where you could
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 as as we specifically can. We certainly don't want to be doing things or making sort of decisions for people which takes away from that clinical intervention because that's super
So we want to be working with the investigators who understand and know whether it be Lyme disease or whether it be long COVID and whatever you know. And that's super important because it has to have value and we'd love to be able to get it right in at the beginning of that journey. going back to something like ME or chronic fatigue, the problem there, many, many years, and I've known
people who have ME. It's the diagnosis and the diagnosis, there's no diagnosis for long COVID, there's no diagnosis for ME or least no diagnostic for that and the problem is when it's left too late it becomes more of a problem.
Kevin Folta (45:03.198)
Yeah, that's a, we've had a number of guests on the podcast series over the years that talk about, 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.
Nigel McCracken (45:15.566)
Yeah.
Nigel McCracken (45:27.405)
Yes.
Kevin Folta (45:28.686)
Last November when I had my bout 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?
Nigel McCracken (45:38.594)
Yep. Yep.
Nigel McCracken (45:46.796)
Yes, so as you said, there are, I
Nowadays, when you're tested for Lyme disease, it's ELISA -based and Western Blot -based, I think. They're the two sort of... And I guess the problem, I mean, I think people who get a tick bite, 30 % will get the round sort of circle, 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. But usually what happens is people will go through an antibiotic treatment for, 28 days,
So the thought is that it misses a lot of people and even following the antibiotic treatment you're just waiting another three 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 our sort of diagnostic is to yes, look at the IgG, IgM antibody production but also look at the interferon gamma IL
are the immune response as well to that and whatever you know. 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
more sensitive but also give some sort of guidance on the cure and 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. we will be and we are sort of working with specific researchers and not just for the people who have
Nigel McCracken (47:50.74)
Lyme disease for a number of years and they've got say some sort of dysfunction of immune system but also for people who are newly diagnosed and to follow them over that you know six months 12 month period and what have you to see if we have a diagnostic that's more sensitive but also give sort 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.
Kevin Folta (48:25.308)
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.
Nigel McCracken (48:58.262)
Yeah, I mean, thing is, is most of these, you we talked about, you know, PD -1 and like three and stuff and things like that. have you know, the hematologically maybe and the solid tumors usually, you know, the solid tumors, need biopsies and stuff and things. That's the problem. You know, unless it's maybe it's, you know, it's it's terrible or something like that. It's most probably a little bit more amenable sort of thing. I get it. But biopsies and you're talking to somebody who's worked for an oncology
last 20 years. It is a complicated business and in that when we talk about oncology and we talk about the tumour microenvironment, that microenvironment is very similar to chemokines, cytokines, oxidative stress. A cancer is slightly different because what it will do is it will shut off all of the things that are there to kill it.
it will, you know, so I think for us other than the CAR T, because it's hematological, when we can actually, we can get the, because it's more of a liquid type biopsy, not a liquid 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 a specific
mutations by a lot of the companies. That's most probably where it's going to be, where you're looking at specific mutations. And there's been a huge bounds made in the field around understanding specific mutation or driver mutations and then targeting specifically those.
Kevin Folta (50:47.356)
Okay, very good. I think I've run out of questions. Is there anything else I should ask you that I left out or that you'd like me to ask?
Nigel McCracken (50:53.537)
no, think we've fairly well covered the immune, adaptive immune resistance.
Kevin Folta (50:57.844)
Okay, well Very good. Let me just kind of ask you for the contact information and then we'll go from there. Okay. Here we go Well, dr. Nigel mccracken and thank you very much for your time today This was really exciting if people want to know more about virax bio labs. Where do they look?
Nigel McCracken (51:18.86)
Yeah, thanks Kevin. You can find all of our social media links on the pages at the bottom of our website, the website being viraxbiolabs .com.
Kevin Folta (51:31.26)
That's V -I -R -A -X, right? That's, yeah, V -I -R -A
Nigel McCracken (51:33.58)
V
Kevin Folta (51:44.68)
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.
Nigel McCracken (51:53.666)
Thank you very much, Kevin.
Kevin Folta (51:56.27)
And let me just finish up here. And as always, thank you for listening to the Talking Biotech podcast. Think about new diagnostic tools and ways in which novel, think about novel diagnostic tools and how they may make a way, I'm just a little bit tongue tied today.
Thank you again for listening to the Talking Biotech podcast. Think about new novel diagnostic tools in 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 Calabra, and we'll talk to you again next week. And that's it. So I will stop the thing here.