[00:00:00] **Trish:** Welcome listeners. We have a very special episode today an interview with Dr. Shirin Kalyan. We wanted to talk to Dr. Kalyan about COVID-19 Canada's COVID policies and what the science says about moving forward during this pandemic. Dr. Kalyan is a Vancouver based translational immunologist She's an adjunct professor at the university of British Columbia and the vice president of scientific innovation.

And immunotherapeutics at a local biotech company. She earned her PhD from UBC in experimental medicine and was awarded an Alexander Von Humboldt. fellowship To study at the Institute of immunology in Germany, Dr. Kalyan's primary interests and expertise are in improving the efficacy and safety of therapies, targeting immune dysfunction and determining how to harness the innate immune system to support recovery from disease.

She is a font of information and she covers a lot of ground in this interview. So we've done our best to link to some of the studies mentioned in the episode, in the show notes below as well as when she testified before the house standing committee on health. It's also worth mentioning that the COVID situation changes and evolves rapidly, but we recorded this episode before some of the most recent developments like the new variant.

Omicron You can follow more of Dr. Kalyan on Twitter at tolling underscore bell. And of course this is not medical advice it's presented for informational and educational purposes only. So please strap in and enjoy the interview.

[00:01:58] **Hirad:** Welcome listeners to a special episode of the Fresh Lens podcast. We're joined today by Dr. Shirin Kalyan from the university of British Columbia. Dr. Kalyan, maybe for listeners, you can give you give an introduction about yourself and we'll get into the topic of the day..

[00:02:17] **Shirin:** So, yeah. I'm an immunologist. My focus is really on optimizing immune function, starting with the innate immune system. And so I, my doctorate was an experimental medicine from the university of British Columbia and immunology subsequently received an Alexander Von Humboldt fellowship to go to Germany for three years where I did my post-doc.

I came back from my faculty position at the faculty of medicine at UBC, but I was really inspired by the work of Dr. Hal Gunn, who is developing biologics Bugs as drugs approach to restore innate immune function in people. So I've now transitioned to actually leading the science at a BC based biotech company, that's actually doing trials in patients with Crohn's disease and cancer to restore immune function. So I'm really my whole focus is really around restoring and optimizing immune function in people. So that's how I got involved a little bit on the COVID front primarily because the approach and understanding of the therapeutics that we're using right now seemed to... the science around that is still evolving.

And we don't really understand how it affects the immune system. And that's where a lot of questions have arisen and, and I've been involved in trying to figure that out as, as the pandemic rolls on.

[00:03:36] **Hirad:** Yeah. And for listeners, I think that's a bit of good background of how we ended up connecting because with the way that things are going in Canada basically around August, we, at least in British Columbia where all of us are we started implementing some more stringent measures than we had before.

More, mostly in terms of mandatory vaccinations or, or implementation of a vaccine passport, that makes it difficult for people who are unvaccinated to to essentially function in society. And a lot of activities are kind of closed off to them at this point. And what was interesting to me at the time that all of these policies came in was that something like 87% of the eligible population in BC had already received at least one shot of, of one of these mRNA vaccines that we have. And so it was kind of strange that at 87% we were still kind of dealing with things. And the question that came up in my mind was, is that last 13% really going to be the thing that makes the difference between you know, we put this pandemic behind us versus not, right?

So I think digging into that story and figuring out what is our way out is kind of what motivated me and a friend of mine to connect with you. And that's how this episode came to be, right? 

[00:04:57] **Shirin:** Yeah

[00:04:59] **Hirad:** I guess, just to kind of lay out a bit of a background when, when the pandemic first happened there were a couple of different countries, took a few different approaches for some they started pursuing a zero COVID policy and in a few cases that seems to have worked for them.

I think New Zealand has managed to pull that off. But for the most part, do you agree with this notion that COVID zero is off the table at this point? Do we actually have a chance of making this go away and going back to 2019 and living in the world that does not have COVID in it?

[00:05:34] **Shirin:** no, I think the consensus around that is COVID is going to be a part of our lives moving forward, just like the flu is and the common cold is. We didn't have any immunity and we didn't know much about how COVID functions. So typically what happens with the virus. As it becomes, part of the virome of of society is really in order for it to survive... if you recall SARS one, it went away because it caused severe disease. Right. And, but you knew you were sick, you stayed put, and it was easy, like same with ebola, those really terrible infections are actually really more, we're able to implement a zero strategy around those because we can capture it, the viruses that become very easily transmissible, and that is allowed when it actually doesn't cause severe disease in the vast majority of people.

I just read a study was actually put out by the CDC saying, who is the one who ends up in the hospital, who are the ones who die of it? Apart from age, which is like the biggest risk factor, it's people with obesity and anxiety related disorders and our response to the pandemic actually increased both those things. So we're actually making the virus worse, the infection worse in people in the way have managed it. Anxiety and fear related disorders is an independent risk factor of mortality with COVID-19 and that's all they see around and have a, had a lot of people reach out to me.

And there, the fear is mismatched from the risk of the disease, in my opinion, at this time, And I think that's that approach in north America, as opposed to some of these like if you look at Sweden, everyone was, you know, was a canceling out Sweden. You know, we were calling them every name in the book with their herd immunity concept and everything they're actually doing far better than we are right now.

Their biggest, their biggest loss was actually around the time when they refused to do the lockdowns that we did. And that's when they had and I have a beautiful graph that shows that most of their mortality and was in people. The majority of those were people over 70. They took a big hit, but if you look out after the vaccine rollout and everything else that was being done, there've been below Canada in cases and deaths. And nobody's speaking about that right now. 

[00:07:49] **Hirad:** Okay, so we said, okay, COVID zero is not on the table. So then the next concern that we should have is about overwhelming the hospital system, right? And this was the first, the very first concern when this pandemic hit the scene with kind of flattening the curve.

Cause once the hospital system gets overwhelmed, then you have this cascading effect of, if you have a car accident, you can't get the health care that you need. So it'll kind of go into a lot of different areas. So Our Policy seems to be that we need to get everyone vaccinated. And by everyone, you know, that number that I gave before was in August, it was 87% of the eligible population, but of course, eligibility was not extended to everybody because the vaccine hasn't been approved for for children, at least it wasn't at that time.

And and so the goal, what we seem to be driving towards is let's get 100% of the population vaccinated or as close to that as we possibly can. Right. And the question in my mind is given what we know about these vaccines. If 100% of the population was vaccinated is the pandemic behind us.

[00:08:56] **Shirin:** Well epidemiologically. It's really interesting that the percentage of mRNA Vaxxed people in a population is positively correlated with cases. So this is, and the, the bad part about it is that the vaccines are less effective in people who need the protection the most. So the older people, they said frail men who are elderly, who, or if you have an underlying condition, I E the people who are most likely to have a bad outcome with COVID the vaccines work suboptimally.

So right now in BC the last account was in the elderly population. You know, more than half, about half of them were already vaccinated. There were fully vaccinated people who died all these outbreaks because we are not acknowledging transmission occurs very readily. So you know, people who have been vaccinated, especially at around the three.

Time points. So we don't know. I think it's really important that we acknowledge what we know and what we don't know about the vaccine. So we, what we know at about the three month time point that your ability to prevent transmission, if you've been fully Vaxxed is not very good. You're more likely to transmit.

There was a study that just came out. There was a reported on, on the guardian and was a fairly large study that showed, and I have to say the UK, you know, the UK scientists are really doing a fantastic job with collecting the data. I think one of our biggest if there's one thing we can improve is data collection here in Canada.

And making that transparent and making it available so we can make evidence-based decisions. But what they found is that the biggest place where transmission actually occurs in households, and they said there was no difference between those who are vaccinated and unvaccinated and transmitting the disease within the household. So I thought, well, they, you know, because what we hear on TV all the time, when we see those health public health professionals come on and say, really, it's the biggest, it's our best way of preventing transmission and infection.

And this is, and that's the rationale for the mandate, right? So if it's not doing that job, and the world health organization actually has come out and put out a statement saying they have a PDF that says they are against COVID-19. Vaccine mandates that, you know, using this kind of overreaching policy health policy, you really have to define what the purpose is.

And, you know, when. Is the end point for, for these vaccine mandates. Now, if you're gone on to multiple booster shots without doing any trials for the long-term safety and efficacy, these are, we call them vaccines, but they're actually nucleic acid delivery platforms. They're not your traditional vaccine. So when people say oh we've mandated vaccines for, you know, eradicated, smallpox.

We have, you know, measles and all these things. These are, those are actual microbial based. They mimic an infection . Those live attenuated bugs are mimicing an infection, and that's why they're sterile. Immunity that sterilizing you don't spread the disease. You need one shot it's really effective.

And we know the long-term, it's undergone a lot of rigorous testing. We've used that kind of technology for hundreds of years now. During this pandemic is the first time we've used this nucleic acid delivery platform. And, and then we called them vaccines. Original definition of vaccine did not include this platform.

But now we've changed that. And we, because it's never been used outside of emergency use authorization prior to this pandemic, we have very little clinical experience with these vaccines. And I think that we're being pushing these out without understanding, you know we heard before, you know, the first vaccine you get is the best vaccine.

And then we saw AstraZeneca sort of disappear from that without any kind of explanation. And then we saw Madonna being like questioned with the myocarditis and peri carditis risk. It's been put on pause and other parts or completely taken off the shelf and in places like Iceland, but we don't even talk about that.

We're not talking about the safety We're like saying. Oh, these are the safest things, you know, you can. You're drinking water. And we, that is not true, we don't know what we haven't had long enough follow up. And especially in children where the risk benefit ratio, and this is what we need, we need need risk stratification. And so we're not, we're ignoring natural immunity. So these overreaching irrational way of approaching, you know, and then giving multiple booster shots.

We don't know when it ends. It doesn't really make sense to me. We should. The first thing I would do is really diversify our portfolio of the type of vaccines we have. And that way people would feel a little bit more comfortable perhaps of getting vaccine those 15% holdout, whatever they call, even people who've already had one or two shots of this one.

And they saying, well, I can go in for like getting a boost. It's not sustainable. Every four months you go in for, you don't know what the consequence of that is, you know, against one antigen. And that's what really helps select for a certain like Delta is became really prevalent in really highly vaccinated places because people who have been vaccinated do not contain it effectively to prevent transmission.

So that's a, you know, those are my thoughts around the current vaccines. We're learning a lot. I think it's a very promising technology. But we were not at a place where we can say you have to take this. And everyone needs to take it, especially since there the full information to get proper informed consent.

You really need to have sufficient data. And the FDA this was written about in the British medical journal, which has been really a fantastic resource in, in breaking it down and opening up the transparency there recently, I think it was just a couple of days ago reported on the the issues with the phase three trial of the Pfizer vaccine, where they said that there was a problem with data integrity and the way that the phase three trial was conducted.

And that's the basis of what the FDA gave full approval of without actually knowing the bio distribution. Aspect of the vaccine. We don't know where it goes and how it's presented to the immune system, how it actually what type of immune response it's triggered, especially after multiple booster shots and children have a very, you know, their immune system is getting educated when you're young.

So we shouldn't be playing around with something we don't really fully understand for. Immune system that really is learning how to differentiate self from non-self and, you know learning how to deal with infectious threats. I was given an opportunity to testify in front of the house of commons standing committee on health.

And I said, you know, you really should be using live attenuated vaccines in young kids. That gives it a good exercise without risk of you know, severe disease. And that's the type of training that engages the entire immune system and puts it all on the same page. So it knows how to function, optimally is actually the best kind of vaccine that you can give kids.

It's not being an anti-vaxxer or COVID minimizer. It's being really evidence-based. 

[00:15:57] **Trish:** I have a question if I might. Because one of the things that I've found really confusing when, you know, I don't have a degree in science or anything, but I'm trying to Wade through the data is what immunity looks like. So some studies, you know, will say. Vaccine immunity is much better than natural immunity.

And some studies will seem to say the opposite and some people are measuring, you know, like antibodies that you might have so many months out. So can you help sort of demystify how, what we call, like having immunity to COVID and what someone who understands the immune system so much more as you do could help us lay people understand that. 

[00:16:38] **Hirad:** I think the CDC actually just puts something out saying vaccine immunity is much stronger than natural immunity, which I think without knowing, without having gathered any data for me, like just on a theoretical basis, that raises an eyebrow. Right. So I'm kind of curious to see what your take on.

[00:16:57] **Shirin:** Yeah, I've actually written. I'll be happy to share with you. There are over a hundred studies speaking to the natural immunity aspect of it. And that's been one of the most frustrating things that there is this misinformation about what natural immunity actually constitutes.

So you, when you, there, there's multiple, not only the durability and the broad spectrum nature of what we call quote unquote, natural. I mean, this is the first time I'm actually using, you know, before we just called it immune you're immune. And when the first vaccine it's a really effective when the live attenuated vaccines were actually built on observing, when someone got sick and recovered wow they were, they were much better protected.

Those are the people we actually hired to take care of people who got sick with the disease. You know, it was those people who got natural immunity and they won't go around spreading the disease anymore because they're immune and they have sterilizing immunity. And that is really important because when you actually get, for example, a respiratory infection, you get it through the same route of administration, the natural route through your nose and your immune system becomes really potent they're in your lungs. You've long lived. T-cells and B-cells, and even your innate immune system has a type of memory called trained innate immunity.

And that was originally really important cause you know, old school vaccines that train the innate immune system, we found that kids who had like, for example, the BCG vaccine originally, they were protected not only against TB, which was what BCG was trying to protect children against, but against a broad range of immune pathologies, because it's sort of like exercising type of th you know, muscle almost in your immune system.

So there were very, it's becomes a lot more efficient. And so when you get, get that natural immunity, that is very similar to live attenuated vaccines. Provides protection on multiple layers of the immune system. And they're all on the same page. And it provides that long lived immunity. Studies have shown that long, the B cells, even from SARS, one people that was like, I don't know, 13 years ago or something like that, they still have those memory B cells in their bone marrow that can respond more effectively even to SARS two here.

And so there is no question. That natural immune. And that's what the basis of vaccination really was. We were trying to harness that without actually getting people sick. Now, if you look at what we're doing now with the single antigen thing, that doesn't activate all those components of it, that's why there's no, your immune system is such, it needs confirmation from multiple sources, right?

It says, if they need immune systems, they, Hey, this is a bug. This is a viruses are problem. It provides that co-activation, that leads to affinity maturation of what we call, you know, this broad spectrum antibody protection, as well as your T cells that help to the B cells to provide that long lived immunity.

So all, that's why it's so potent, that's why it lives for so long. And the best thing, you know, your immune system has a certain amount of resources. So if it's something that becomes common in our society and you get exposed to that antigen. You keep evoking that memory and it gets stronger and stronger each time.

Right? That's why I think leave the people who have recovered from COVID alone. There's a 27 fold, better immunity in people who had natural infection in Israel. And they actually collected data really thoroughly and it's quite transparent, their database. We don't have that here for whatever reason. And they had an eight fold reduction in hospitalization compared to fully vaccinated people.

And so that, to me really underscores and that's one of a hundred different studies that have spoken to the natural immunity concept. And so we're not, we're not stratifying where we're treating everyone the same way. One of the concepts around the natural immunity questions was because antiviral immunity is actually, it's a, it's a type of, it's not all antibodies, it's actually T cells. And then you have natural killer cells.

And the, the kids, they, they found where people with very mild or asymptomatic disease didn't seem to develop very much antibodies. And they were like saying, oh, this, this means that their, their memory's not so good or their immunity's not so good, but there was a beautiful paper. I, I don't want to misquote, I don't know if it was in cell, but it was one of those top notch articles where they actually followed kids and their families and they, they noted the reason why kids are so asymptomatic is their innate immune system is so efficient, but it didn't compromise their T-cell or B-cell responses at all. So that was, it's just that they're better at that containing it. And that's an initial response was just so potent that it retained at at a very local level.

And so that was the, and they had, you know, long-term B cells and T cell responses that were still functional. And I think that's the key thing. You can't actually get rid of infection and not get memory from that. And so that the there's this fight against, you know, you know, natural immunity is not a thing as the first time I've ever heard this thing because we were trying to with vaccination, that's what we're trying to achieve is that memory.

Right. And so, and it would be far longer lived than four months.

[00:22:09] **Hirad:** And just, just out of curiosity, even theoretically, is it ever possible to have a virus that we can have a vaccine for that would give you a better immunity than what you would get? If you just contracted the virus, assuming you didn't die from it.

[00:22:28] **Shirin:** right? So that's the, that's the rationale like if, if you don't die for it, like if it was a fatal disease and I would, for sure, you know, say let's go for the vaccine. Right. But I can't really, I don't have an example that I can think of. I know, for example, the polio vaccine, you, you know, you didn't do well with getting the actual disease, but the polio vaccine was much more preferable in its immunity.

But it was also like a live attenuated type. It was mimicking a natural. So when the disease doesn't cause more damage even if you get memory, then I would say, you know, those are the examples where the vaccine definitely would provide the better long-term health outcome. But

[00:23:16] **Hirad:** I'm just talking about

[00:23:17] **Shirin:** that the immune response.

[00:23:19] **Hirad:** Yeah, the immune response.

It just seems like the idea of what a vaccine is it like you said, it's based on your body's immune response. So I think this notion that we are going to cook something up in a lab, whatever it is that is going to give you a better immune response than yours.

I was just that doesn't really make sense to me.

[00:23:37] **Shirin:** Yeah. Like, I can't think of, you know, there might be people in the audience who, who, and there are people I have to say that have a different opinion. Cause I hear it all the time. I have a very different opinion on, you know, a whole organism fighting that host pathogen interaction. All aspects of the immune system.

So some people might say, oh, your antibody responses after vaccination are so high, but is that, does that mean that your immunity is so high against this pathogen? And this is where I sort of, you know, diverge in my opinion of things like having high levels of serum antibodies for a respiratory infection, doesn't necessarily what it means is that if it ever, if you're older and you're you're, the infection goes bloodstream, then that would be really good protection.

Because you have neutralizing antibodies against it, but it doesn't mean that you have better immunity. better immunity is like containing it at the at the point of infection. Right. And so that's why it's not a sterilizing mode. One of the things I've been trying. This is a little bit of a segue.

One of the things I've been hoping we would have in BC is like a lot of people have been we've not been exposed to many respiratory infections because of the, you know, lockdown and everyone's wearing masks. And now it's flu season. It's RSV season. All these colds are coming around. The best thing you could actually do.

And we couldn't find it anywhere is to get that live attenuated Inter-nasal flu vaccine FluMist it's not available anywhere. If I was leading the healthcare policy, I would say everyone, you would be protected a little bit against, even serious. COVID you're priming your innate immune system in your mucosal area.

You would be protecting yourself against the flu or any other respiratory thing, because you're, that aspect has not been well exercised. It's like, you know, you're trying to run a marathon and you haven't even gone up for a jog. So I'm like saying, this is what we should, if you were really thinking physiologically and immunologically, you would be digging that flu mist thing and providing that to everyone and you would prevent the serious morbidity, but that's like, they're giving for adults, they're giving the shot again.

They're giving a systemic immune response. It's not through the, the general way of how you get infected by these things. So, you know, I think that there's a little bit of disconnect from understanding the immunological concepts and the way health policy is actually delivered. And I think that if it made more sense and if there were more rational and evidence-based, they would have greater uptake and trust in the management, because a lot of people looking at it and saying, you know, it doesn't make sense .

[00:26:08] **Hirad:** for sure. I think we'll probably be paying for that far longer than we'll be dealing with cOVID. 

You said a lot of things that I kind of want to double click into. So. Okay. Just as a, as a way of analogy for for the listeners, this idea that we have vaccines are safe. this is a talking point that a lot of people use is vaccines are safe because we've been using them for hundreds of years.

And you know, we have eradicated all sorts of bad diseases using vaccination. So why are you against it? To kind of put what you just said in different language, that's kind of like saying sports as one word, encapsulates everything from cricket to American football. And it's like saying cricket and American football are the same thing, right?

This mRNA technology that we're using right now is fundamentally different in how it elicits an immune response, than everything else that we've used in the past, is that right?

[00:27:05] **Shirin:** Absolutely. 

100%. Yeah.

[00:27:07] **Hirad:** Okay. And so why are these vaccines not solving the problem at the moment? What do we know? You mentioned the fact that there is waning immunity. We know that a couple of months after vaccination, they're definitely not stopping transmission.

transmission

And, but are they stopping hospitalization is immunity against severe illness waning.

Do we have any data on that?

[00:27:32] **Shirin:** So that's really, that's an excellent question. So and this is where the risk stratification really comes into play. So it seems like, and I was just reading the latest on the Lancet they have a pre-print of a really large included 1.6 million people from Sweden. Sweden is one of those countries.

They have really, we don't have a control group anymore. So this is the real problem with it. Not only do we not collect data, but we have completely messed up any kind of control group. So it's, it's hard to say you know, use the data that we're producing here. Just the way it's been collected and managed, but here what I hear consistently is that a serious disease, at least up to the first six months and potentially up to eight and nine months, and mortality is significantly protected with, with the vaccines that we're using. Right now, in at-risk populations, but the data was just reading from the Sweden study that looked at it longer and they have a really good control group. And I think the, the caveat there, and they didn't mention it because Sweden might not be the most optimal. They were looking at vaccinated, unvaccinated populations.

And they found that after six months, those people who are older males and who are frail there really wasn't as much protection against severe disease and and death than has been reported. Previously. Now I think the problem with that study was largely because they didn't account for natural immunity that might be present in their population by that time.

So if you've already had it, we know you're not gonna, you're not going to be hospitalized. And you're, you're probably not going to die. And that's why that that comparison lost significance down the line later on in their population, they didn't seem to have accounted for that concept. So we actually need, if we're really gonna understand this effectiveness, we really need to break it down.

Not only by risk of death and hospitalization, because apparently in those who are most likely to die, The efficacy is much, much lower than the 90%. And and there might be the biggest benefit might be for people under 60. And so they have very minute. This is where we need to look at not relative risk, but absolute risk.

Like what is the percentage of actual is a one, 2%, you know? That's the, the diff that's the actual number that we're never given. You know, if, if like two people. Died with who are fully vaccinate versus four, there would say, well, that's a 50%, but they're not saying it's the difference is 2%. So that's the difference between absolute risk and the relative risk because in, in young people, especially those with no comorbidities death is very, it's very, very, very, very small, a number of people.

And it goes down significantly with with age. 

So when we're looking at, you know, the reduction in serious severity, it definitely helps in the first few months for people who are at risk, but we don't know, and this is the problem. We don't know how long, how durable that immunity is. And the short live, you know, th th the short life of this immunity is I've never really.

Seen it before. Like I think this is, this is where the science is still evolving. We don't know how long it lasts. What happens when you give them multiple booster shots? Do you get, maybe you get, you know, like when you get desensitized to certain antigens. We don't know what, what is the consequence of this constant boosting with this technology,

[00:31:13] **Hirad:** So I want to dig into something you just said, typical vaccines that we have used in the past. They, you know, that it's a weakened form of the virus and your body essentially learns the virus' genetic code, so to speak and kind of stores it away and knows what to look for in the future. In case it encounters that virus again with the mRNA vaccines we're injecting the genetic code for one part of the the sars-cov-2, which is the genetic material for the spike protein.

We're relying on the body to use that, to create its own copy of the spike protein, then your immune system is responding to that. Right? So no matter how many of these shots you get, your immune system is ever only learning to respond to the spike protein of the virus. And my understanding of this is a few different risks come from this one.

It's actually, because it's such a small surface area of defense a mutation in this spike protein could essentially nullify the immune response. I didn't understand the second part of what you said about having so many of your antibodies kind of targeting this one?

Spike protein. If you could elaborate on that, that'd be great.

[00:32:26] **Shirin:** Yes. So we keep expanding our memory of this. Like each time we give it, you generate, you know, you have a bloom of these antibodies cause they they're receiving it. Again, so they think this, this foreign thing is again, in our, in our serum, the messaging, the instruction of what that means is unclear to the immune system, from what, what my reading is.

Every bug has a type of programming and elicits a certain type of strategy from immune system. So your antiviral immune response is pretty different from my anti parasitic response, which is different from an antifungal response. Cause there are different types of pathogens and the immune system has different strategies and different cells that are mobilized against it.

Now in this, mRNA thing, where is that instructed? There is no instruction like. And what's interesting. It's not actually activating those evolutionarily conserved pathways, which for immunologists out there, no, as like toll, like receptor pathways or pattern recognition, pathways that go through a certain signaling.

Pathway that activates a certain type of strategy and immune memory. This seems to bypass and is generating a large amount of antibodies. There seems to be from my reading, there are certain types of TIF, molecular cells and B cells that are w are generated, but it's not of the same type of activation pathway that he would normally get from a virus, for example.

So we're generating a large number of antibodies toward a pathway that's not usually used for antiviral immunity, and we keep boosting that over and over again. And because of the way these antibodies are generated in the programming, it's going through. We don't know, at least, I don't know what the longterm boosting of the same type of antibodies would you get class switching and some, all of a sudden it'll say, oh, this is, you know, when we get exposed to, for example, you eat a lot of garlic.

You're going to have antibodies got garlic, but they're not anti infectious. Right. They're, they're sort of like saying, oh, this is not a problem. We see it all the time. You become tolerized to it in a way. So my question is in certain people, certain and everyone's immune system is programmed, you know, through your life experience, epigenetically you're, you're you respond differently.

Like, you know, one person would respond very differently to certain things. And so. People I'm wondering whether you would even with multiple indeed, even depending on, they don't have clarity on when the timing of these booster shots should be. You know, if they're giving it too soon, I think this is one of the problems.

If you give it too soon, you might not have a very good response. It might be something that, you know, there's a lot of antibody production happening, but you know, I don't see where the infection is. Your body can sense infection when it's there. So it's sort of like, oh, I'm being psyched out. There's nothing happening here.

And so there, there are a lot of questions that remain unknown and having a large amount of antibodies, your body doesn't like that to one thing that is not seeming to be causing any problems in the body. It might just switch that off and say, Maybe we shouldn't be making so much antibodies against this thing.

And so we don't, we haven't done long-term studies where this first time you're using it. That's why the science keeps evolving, you know, should we be mixing and matching? What should be the timing? This is typically done by a clinical trial. Like you have this figured out. Now I'm not saying in the middle of a pandemic year, I might against new concepts and everything, but really don't, you don't put get this 90% of your population.

This is where all your eggs are in this basket. Why aren't we going? Why are we getting those inactivated, well-adjuvanted old school vaccines into the mix, right? At least then you'll have different antigens that are recognized. The problem really is having a population with only one type of immunity.

That's what causes this, the spread and mutations and selection for more viral and transmissible strains of the virus.

[00:36:24] **Trish:** Can I ask a question about the vaccines. When I went to go get my second dose in BC, the policy was you just show up and you take whichever one they give you. While they actually weren't even telling you until you like got in the chair and we're about to get the job. I remember what they would say to you was your immune system doesn't care about brand names.

And so like with the implication being that like, you know, it's all coming from the same factory and they might slap a Pfizer on the outside or a Moderna label on the outside, but that they were all the same thing, but I don't think that's true that they're all the same thing. And like, this must be a nightmare for people who are trying to study, you know, which, and mixing and matching.

I don't know. Do you have any thoughts around how we are? Just like people are getting kind of the gambit 

[00:37:13] **Shirin:** yeah, that is, it's been one of those real big failures. I think of public health was the, the misinformation and the lack of correction later on . There's a difference in the risk factor, but also the efficacy on the other hand. So because of the more potent response that people with who have the Pfizer vaccine actually lose efficacy or this infection prevention of infection faster actually than the Moderna.

You know, and as I mentioned, AstraZeneca was, was taken right out of the pool that's available now. And all those steps were not taken first by Canada. It was taken by other countries. And then we sort of like, we always follow and I think we have to stop following for whatever reason we need to have better, better data tracking, and we need more transparency.

So you need to explain, so you don't lose trust. People don't know, you know, say, well, I, I was listening to the news and you know, they randomly pick people on the streets and they said, oh, are you getting your booster shot? Third booster shot in, in those who are available in this woman said, well, I got my AstraZeneca.

I don't know if I should get, you know, my, my vaccine is no longer available. Given, you know, and I just realized when I listened to her at that time that they haven't really I'm on top of it. Cause I'm following, of course, I know that they're mixing and matching all kinds of things all over the place.

And and I realized they had didn't really communicate to people. You know, where were, where was their decision coming from? What was the evidence that they're basing their recommendations on? I think a lot of that is not being conveyed clearly. It's just like they go into their room

decide what they're going to do and come out and just tell you this without any kind of explanation. And I think this is the wrong strategy. Because people are not understanding what the heck is happening. And so I think that is problematic because the better informed people are. Then the better the outcome is going to be for, for the overall health.

They need to be able to figure it out. The fact that none of the life like you it still annoys me. Cause I remember someone had told me they were listening to the minister of health at that time. And this whole concept around vitamin D supplementation, or there are a lot of observational studies, like we know vitamin D affects immune function, even in chronic disease prevention of some auto immune disorders.

And there seems to be a relationship also with COVID outcomes. It doesn't, it never hurts anyone. Like you're just, but to call it fake news or like not a thing, just like natural immunity... 

they're taking all of those things that would actually help people stay healthy overall and, you know, go and play sports outside, go, you know, live the, be as healthy as you can because in doing so, your, your risk of severe COVID is going to get minimized. 

So I think that has been an issue of public health is this clear information and what they're basing the evidence on and sort of pretending all of this and it might be the scary thing might be that they actually don't know the difference. Of how these mRNA vaccines work. Cause I remember when I'd given my testimony, I had actually told them in June that the AstraZeneca is, is, you know, when you have a viral vector what's going to happen the second time you give it is because you were developing antibodies against the vector.

You're gonna wipe that out. So the efficiency of a booster shot is not going to be very much. And now they're recognizing that those viral vectors didn't actually give you much immunity. And it was most likely because of the fact that you have developed antibodies against the vector. And that's why taking another type of vaccine, like the mRNA would give you a better immunity than, than the another viral adeno virus vectors, because everyone's there, they're all using the same vector for everything.

One of the frustrating things is exactly, as you said, that they were comparing it to traditional vaccines. And that I think is really the biggest misinformation out there because people are going around saying, you know, you're, you've, you've done this for, you know, all the time.

They're not recognizing this is a platform we've so little experience using you. Can't you see all the missteps that we've taken on. Like we were just figuring it out. Well, you know, we're making up the decisions as we go without really good evidence. And because we're doing that, it's fine. If you, if you're in, we're in the middle of pandemic, we don't have the luxury of time.

I get it. But you don't go ahead and mandate something that you don't understand completely, especially when there are other options available, like covaxin. Got, , available. We have Novavax, valneva's whole inactivated vaccine with a beautiful adjuvant that stimulates antiviral immunity. Why aren't we bringing that on?

And, and helping at least the younger people who have have clearer safety signals there, why aren't you making that available to other people? And you might not need so many booster shots after these.

[00:42:12] **Hirad:** So perfect. So those two the last two things you said are great segues into where I, wanted to go next. We've heard a lot about, you know these vaccines are safe and effective and why are more people not going to take it? So with regards to the mRNA vaccines that we have available today, some people are uncomfortable taking them partly because they are so new they have only been approved under emergency use authorization and people are kind of afraid of having some kind of medical intervention that is not fully vetted. Do you think some degree of concern around mRNA vaccines is justified and based on what we know today, where do you think the risk is that would justify taking the mRNA vaccine?

And in terms of who should be taking it and who shouldn't be, or should it be everyone? Because there really isn't any good justification to be concerned.

[00:43:08] **Shirin:** Yeah, so we are hearing the narrative in the public is the lat ladder, right? That these are the safest and most effective things that you could be taking. The, the adverse event reporting system in the states suggest otherwise. And the reports out of Israel suggest otherwise they're actually take telling people not to exercise after getting for at least four weeks, especially young men.

I think the problem really is from my perspective is the bio distribution data. Like we, if we don't understand if it's a little bit of a.

[00:43:41] **Trish:** Can you explain what bio distribution data 

[00:43:44] **Shirin:** Yeah, good call. So bio distribution, and I think it's important, particularly for this kind of technology is after you inject it, where does that go? Which cells does it enter and which cells are making that mRNA thing, ideally, if you want a good immune response, you don't want it to be your heart cells.

You don't want it to be on your nervous cells because you're launching an immune response against this, right? You want professional antigen, what we call antigen presenting cells. We want your, you know, things like dendritic cells or your monocytes, and they can coordinate a better immune response and memory.

But because this is sort of I tried to find some of the bio distribution studies that I haven't been able to find any for the actual mRNA vaccines that we're using for. Protein. But I did find like long time ago, I wouldn't say it that long during 20, 19, 20 18 before the pandemic, which seems like it's decades ago now.

There were a lot of biodistribution studies and actually papers describing some of the hurdles of using them in vivo in people. And one of them is like, you can't really control where it's going. It seemed like a lot of it went to your liver

[00:44:54] **Hirad:** So these were pre pandemic by distribution data on what

[00:44:58] **Shirin:** in, in animals in animals, because they've been trying to develop, like these types of technologies have been in development for a long, pretty

[00:45:04] **Hirad:** So those are the ones that you're talking about also about MRN vaccines, but our MRA technology, but it was pre pandemic.

[00:45:12] **Shirin:** pre pandemic. Exactly. Like around 2018. A lot of these studies came up down and they were actually looking for liver disorders because it goes nicely to the liver, but it's hard to, to get it to go exactly where you want it to go. And. By fluke. If you can see it go somewhere else it might not end up so well, so maybe there's even a different bio distribution depending on your physiology, right?

Like it seems like young men and I don't know why it's young men in particular, what is it about young men that makes them more susceptible to this myocarditis pericarditis thing at a fairly heightened, like the, the incidents were not, we're looking at actually symptoms. They're going to be subclinical.

Aspects that we're not actually looking for. And we should be looking for, you know, what is doing follow-up because maybe those people who are not as active are still getting that heart damage, but it's not as symptomatic because they haven't stressed that system outright. And in older people, you probably the background noise, the number of older men with the heart disease is so high, that noise to, you know, signal ratio may be quite, it's not high enough to actually see it, even if though it's occurring.

Right. Because they. Through the background noise and because it's so low in, in young people that you can actually see, oh, wow. Like, you know, this is causing a lot of problems. Especially when the system is stressed. So that's what biodistribution is essentially where it's going and how it's being made and which cells are making it and how it's being presented to the immune system.

That's just basic. We would need that information before you get drug approval, especially for a new technology that's depending on expression of a, of a protein. And that was one of the things, there was a petition by, you know, a number of people. And this was published in the British medical journal before the FDA's approval.

They said, we need at minimum, despite our distribution thing, we need two year follow-up of pivotal trial for safety. These are just like, you know, basic things that you would want to have in place before you give full drug approval. And they went because they wanted to put in the mandates, the overrode, these, they expedited the approval before getting.

Necessary data. And and then after there was also approved on efficacy data that later on, you know, they wanted a 50% efficacy and they reported on having over 90%, but that was within two months. Like if you look at six months, what's the efficacy, it's less than 50% for the Pfizer one. So this is the problem.

It was based on data that was not only incomplete, but didn't stand the test of time only six months. So that to me is like a big red flag. And this has been reported on there is, you know, if you follow the, the editor of the British medical journal, he spoke on this very eloquently. And he's one of those people who is not afraid.

You know, there is a lot of pushback for people who are in the medical community and the scientific community who are again, The narrative that is being put out in the public. And so that kind of censorship, especially when there were really well-regarded scientists who did epidemiological studies on myocarditis, and it was completely factored, you know, it was peer reviewed and the journal, it was just published by Elsevier actually put a the first time I saw it, they were saying that they were going to put a hold on it or something like that and take it down ... . It wasn't something that the data wasn't done right. Or the analysis was wrong. It just was not congruent with the messaging of the time. So that to me is really problematic when we don't have a good handle on what actually is the adverse effect profile who is getting it.

And so. I do think that, you know, , if it was the only option, right. To protect those people that we have identified, this pandemic has been going on for a couple of years, we know who gets seriously ill, who gets hospitalized. We know we want to make sure. And if we were doing it things properly, we would explain to that population and say, look, you're really, if you get this thing and you're going to get it because it's, so now it's going to be highly prevalent in the, you know, you're better off being protected.

And, you know, some people have even been floating around. Unfortunately, some people like Joe Rogan was the first person to suggested. So now, you know, it's been dismissed because whoever says at first, like if it came out of the wrong mouth at the first time, but it's been echoed by other time, you know, the concept you're, if you have some immunity to the vaccine and then you get exposed to a national, get better immunity, like natural quote immunity, Then, you know, that might be the best way because that's actually a sterilizing type of immunity.

You're not going to have the cyclical thing where you keeping this thing alive and prolonging the agony of this thing. You, you're going to have somewhere like Sweden, where their, their level of actual herd immunity is pretty high. There, there are these concepts around where, you know, how we can make the transition into an open society, less painful for people who haven't had COVID already and are petrified of it. You know, just saying, if you have some immunities of vaccine, you got to likelihood, according to the messages, you're going to handle it a lot better than if, if you, you know, didn't have it. And Those are the tab because we are going to, we can be sitting in our basements all the time and just waiting for this.

It's, it's a, you're not going to get zero COVID. We need to diversify the different types of vaccines available. The young people are the biggest ones who don't have any vaccine immunity yet, but the data is showing they're going to be just fine.

And so I really hope that there's no mandates on, on children's, especially the way the phase three trial was done with Pfizer.

It was, it was not to me, a very rigorous or committed. Trial with a couple of thousand kids with not actual endpoints cause nobody really got sick. Nobody got severe disease, but what was interesting, those were natural immunity had the, you know, had no infection whatsoever. That that's what that trial had shown.

And and you wouldn't want to immunize a child who's already had COVID so they would have to recognize, because I think the risk factor is going to be a little bit worse you know, in terms of severity of symptoms, et cetera, to the vaccine. So so I'm hoping that the recognition, you know, immunological currency through infection is recognized in other parts of the world, for whatever reason it is not in north America.

Let's, let's come back to looking at the evidence and then we'll have a better handle on the pandemic.

Moving forward.

[00:51:49] **Trish:** Do you think we should be concerned with how we, the vaccination policy might be changing the selective pressure on the virus? Like, so I think Hirad has, could maybe state that question better, but I think this is a discussion Hirad and I've had amongst each other. And I don't know Hirad if you want to try and rephrase that 

[00:52:12] **Hirad:** Yeah. So there there's, there's a study. I think I came across it, I think it's from 2015 or 2016 that basically showed in a, in a lab setting. So obviously it's not about diseases that are out in the wild, but in a situation where you have a population that is vaccinated against severe illness or death.

But, but vaccinated such that transmission is not stopped, which this is exactly the vaccines that we have today. They're not stopping transmission, but they are stopping severe illness. That you are essentially creating an evolutionary selection pressure for more virulent strains of the virus, such that, these strains , when they meet an unvaccinated hosts, their impact is going to be much higher than they would be otherwise.

So one kind of a picture that kind of formed in my head when I read that was we've essentially created a situation because evolutionarily speaking, as we talk on this podcast, a lot about it, we kind of started from the podcast from evolutionary biology book club. So. Evolutionarily speaking a virus, a new pathogen seems to have a selection pressure to not kill its host over time.

Right? So it might be extremely lethal when it arises, but over time it kind of gets more and more mild because there's kind of a, somewhat of a symbiotic relationship when the, the pathogen wants to keep its host alive to be able to reproduce and spread. Right. So this is my understanding is that the pandemics we've had in the past have kind of become endemic through a combination of natural immunity and the lethality going down over time. And part of that is because they do kill a lot of their hosts overall, but you would expect that at some point a mutation will arise that will be less lethal and that will be more successful evolutionarily. And so that you'll kind of get that going when you have a population that's already vaccinated.

So People are not going to die from the, the virus that selection pressure is removed. So now there's no more incentive for the virus to be less lethal, which means that if you're unvaccinated, you're never going to get to that end point where you can you'll get a virus that is just kinda mild.

Right. So I don't know this is kind of a theoretical picture that based on that study and like a little bit of my evolutionary biology background, I've I've kind of cooked up in my head. So yeah, I don't, I don't know if it actually makes any sense. 

[00:54:41] **Shirin:** That experiment, it was a very elegant study in which and I believe it was, it was published in PLOS biology where they were actually using a bird flu and they called it imperfect vaccination such that transmission. It was sort of leaky if you will, transmission wasn't prevented was suboptimal, but there was efficacy in severe disease and it does ring. It has similarities to what we're seeing with the platform vaccines that we are using for COVID-19 right now, at least in north America, we do see this it is not really great at preventing transmission, but there is efficacy in preventing severe disease and or hospitalization. And I think that's in the same countries, what has been noted is that, you know, cases are going up and hospitalizations, at least up to this point have been by far, especially proportionally more in the unvaccinated group, which is very similar to what.

Experiment in which they were testing this out in that chicken virus, vaccine had showed that it was, it made the disease worse for those who didn't have immunity. But it did protect those who had vaccine acquired immunity. And there there is, we haven't really studied whether the same phenomenon is occurring, but there, it certainly strikes a chord of, of similarity when you're looking at what is happening across the globe where we may be selecting for variance that in, in vaccinated a group, of course, when, especially when we have selected immunity on one part of the the virus. So most of the vaccines are against the spike protein. So of course we see that those mutations that occur in the general population are the ones that spread are going to be those ones that are selected for, because of transmission is allowed amongst people with the same kind of immunity.

So I, I don't think it's outside the realm of possibility that that's exactly what we will be seeing, especially when the viral load it seems is as, as high in those, what, in what we call breakthrough infections that there as an unvaccinated person, what is interesting though, however, and maybe that's the silver lining is data from the office of national statistics in the UK show, people who have been previously infected and it was found to be rare to be reinfected, but those who did get reinfected actually have very low viral loads and their disease was very mild compared to the first more symptomatic sort of disease that they had when they were in their primary infection.

So that is to me. And that. We would want to have that kind of immunity that is more, you contain it and, and you keep viral loads low because when you keep viral loads low you're, you're preventing the ability of the virus to get all these mutations. And what we will see is that. It is amongst those people with no immune where you have higher viral loads where these mutations occur, and once they've occurred the selection process and those that will be they'll survive in a population that's highly either vaccinated or have a certain type of immunity would be those ones that can still spread amongst people with that kind of immunity.

So if that makes sense. So I do, yeah, I do think that Having a single target approach. This is essentially what we can sort of favor in terms of selection for variants.

[00:58:18] **Hirad:** Right. Would it, I guess to my mind, it wouldn't really be that big of a deal. If we could vaccinate everyone and transmission kept going, if everyone was vaccinated, you know, there wouldn't be this segment of the population that is disproportionately affected, but there's also the problem that several months after vaccination, you're basically like being unvaccinated. So we end up in this situation where we have to keep kicking the can down the road. Is that unreasonable to say or? 

[00:58:47] **Shirin:** Well, that, that does seem, so there is this, this differential, and I think we're trying to understand.

Because I think the science is, you know, keep saying it, the science is still evolving around this platforms. We haven't had a lot of clinical experience with the type of vaccines we have. So it's really interesting that you know, the, the efficacy for infection significantly declines like let's see within six months of getting your two shots, but what seems to hold and there is variability depending on your, your demographic, if you're older and more frail in that protection against severe disease may also decline, but in general, more healthy people. There is still this protective effect against severe or hospitalization with with the vaccines. And to me, it's interesting. Why is that primarily through some antibody producing cells that are still around and can capture that outside.

So understanding that phenomenon, what type of immunity is providing that protection would be important. My question would be if, if, if we have a really highly transmissible version of, and I think the Delta variant is, is highly transmissible, still amongst people who are also fully vaccinated.

If once they get you know, natural infection type immunity, whether it's. We can sort of stop that continue kicking the can down the road. And and I think we have to do more studies. We need to be tracking. Okay. People are, is, is the transmission going down in a population that has like our population?

We're like a 90% almost vaccinated at this point in time, at least in British Columbia. Whether or not. People who've had, who get infected after being fully vaccinated. Do we stop, you know, do we see an attenuation of the number of cases over time? We are seeing this in different populations. Like for example I mentioned Sweden before Sweden has they didn't have a very high vaccination rate when they first got exposed to high burden of infections earlier this year. But we're seeing cases are quite low in, in Sweden right now and we're seeing the same thing in places like India. And I think also Japan had this weird, really high and then just plummeted. And we're still trying to understand, you know, what was it that happened?

Simply shut down that it wasn't really scary increase in cases. And what, what is the scary part about it is, is really around whether there is sufficient resources in, in the healthcare system to deal with a high burden of people who need resources in the hospital. But here, I think we're at a point where things seem to be.

Under pretty good control. And and I think now what we really need to do is collect data and look at, you know, what is the contribution? And then we haven't done this here. What is the contribution of an infection acquired immunity, either alone or in the background of someone who is vaccinated and can that can we sort of.

Rely on that now more for providing the, the protection we need and allowing us to be a little, have a little bit more breathing room. Cause we're still all holding our breath at this time. And I think we, we overreact every time we hear about, you know, we're doing this daily case count and it's not mentally healthy looking at this without context.

[01:02:20] **Hirad:** The singular objective that I think we need to drive towards is getting back to living our lives the way we did in the past. And, and knowing that we're not going to run the risk of our healthcare system collapsing because of this pathogen.

Right. So. from what I've understood from these mRNA vaccines, their effect is good. It would be better than not having them, but it seems like they're always kicking the can down the road. And when we are doubling and tripling down on a solution that is not a permanent solution.

To me, it seems like we need to diversify our arsenal a little Right. So you mentioned a few things, so I'm happy that we have these antiviral drugs, cause at least you know, that's another angle of being able to attack this disease. But you mentioned a few other vaccines that are, I haven't heard of before.

I, can you talk about them a little bit and how they're different from the MRN vaccines and where they're at? Like, are we likely to get them or unlikely to get them.

[01:03:18] **Shirin:** So the one that's farthest ahead is covaxin which just got just a few days ago, got a authorization by the world health organization. So it's a recognized they'd met all the efficacy and safety endpoints seems to have around 70% from what I recall reading from our press release against the delta variant.

It's a whole inactivated vaccine, which really cool adjuvant. I it's activates what we call TLR seven TLR eight, which is toll-like receptor seven and eight, which is your endogenous innate immune recognition. Molecules for viral infections. So it gives the whole dead bug and combines it with a signal to your immune system.

This is from a virus. So it can launch, you can get that strategy against this the vaccine, your immune system sort of understands where this, what the problem could be. I like the strategy I think is super brilliant. I'm not a fan of these... Aluminum based , aluminum hydroxide, which is someone like Sinovac has that it's also an inactivated.

I believe it's made by a Chinese manufacturer, aluminum hydroxide. And this is where the problem, if you go back in the development, manufacturing of vaccines, you know, alum was part of what we called. Fords adjuvant and it's a little bit became, you know, once something gets known as being an adjuvant, then it gets used but it's not really an adjuvant. Those, those vaccines were using bacterial vaccines with dead bacteria and the aluminum interacted and made , the components of bacterial outer cell membranes, which included lipopolysaccharides, all these things that are not present in viruses, but it became because it became known as part of an adjuvant people just add it to a dead bug and call it an adjuvant when it doesn't really function very well as such

[01:05:06] **Hirad:** Sorry, can you define that term?

[01:05:08] **Shirin:** Oh adjuvant? So adjuvant is something that's added to a vaccine that makes it more immunogenic to your immune system that it activates. If you just give dead proteins, you know, like what a dead virus would be, your immune system won't really be launching a very strong immune response to it. So there has to be something that is give some sort of signal, like a dangerous signal that this is from a bug.

So the best one to give dangerous signal of those pathogen associated patterns that typically go along with that kind of infection. So the one that covaxin this is from an Barat biotech, which is an Indian biotech company, and they actually took the adjuvant, that was a new formulation from an American biotech.

It was a, I believe it was actually partly funded through the NIH program a while ago. So it's a really cool, new, adjuvant that is really effective, I think, or a smart strategy. I wouldn't say effective because that time will tell about its efficacy as we roll out. But in terms of strategy and innovation, it is really smart because it triggers and that stimulant, that coactivation that that immunogenic component to it that would come from a virus.

Typically from a viral infection. So the adjuvant is a really important thing because what we know from historically, for example we had kids get RSV infection, respiratory infection. And I recall they were trying a number of vaccines had failed. And the reason they failed is because they didn't have a good adjuvant that activated that innate immune stimulation that gave long-term adaptive immune support to the vaccination.

So they, they recognize if they put in the right adjuvant, then they could get that affinity, maturation and long-term immunity to the vaccine. So the adjuvant to me is actually the critical component of it. And I don't know what part of, many of these nucleic acid delivery platforms would function as an adjuvant for that long-term... So covaxin is one of them. I like the fact that it's a whole inactivated one because it has multiple antigenic epitopes. So I think if you wanted to vaccinate someone who's already had COVID, this would be the perfect thing, because you would be activating all of the different androgens as opposed to one under selective pressure.

Right. And so That would be just thinking strategically, that would be the best approach. The other one that I would say ... covaxin has been approved by the world health organization and it, in July of of this year, they had actually put in a submission to health Canada for, for approval.

Now that doesn't mean even if health Canada approves it, it doesn't necessarily mean that that they'll procure it. So we were procured a lot of these, the same sort of new platforms, but we the only old school type of vaccine.

It seems like Canada has intention. So far of procuring is Novovax and novovax is a subunit vaccine. You can think of it like a processed version of the whole of vaccines, where they, they express the some viral protein. And it's also focused largely on the spike protein. And I believe it's a really interesting technology because they believe they have these express and moth cells the proteins, and then they purified the viral protein and they add an adjuvant called saponin, which is from a plant.

It's not an antiviral. It's not, it's not, I don't favor it as much. If I have favorites, I have a favorite with covaxin and Valneva. I will talk about next. So those are my favorite, but novovax to me is more traditional type of vaccines. And maybe, you know, maybe our trials in younger people should be using novovax as opposed to some of these mRNA based technology given what is known about their adverse effects. And lastly is, is Valneva, which I really ally. I like valnvena a lot. Valneva is a French biotech, I believe. And they had co-produced this with the UK national Institute of health. This vaccine, it also has a really smart adjuvant, so that and to the immunogenic component of it, it's called CPG.

So it, it activates the type of immune response we've been using CPG for. Activating the immune system to give both an antiviral as well as anticancer immune response or for intercellular things. And I think it's a really brilliant formulation and they did a none inferiority a test against AstraZeneca in the UK.

I believe it was. And they showed that their T-cell and B-cell response was significantly better than the AstraZeneca vaccine. It's just, it takes, it's quite, it's quite courageous of them to do a non-inferiority trial. So what that means is you're taking something that's approved and you're showing yours is actually better as opposed to a placebo, which has no effect like your, the bar is set a little bit higher.

So they, they had PA promising results from that. And they're also in whole inactivated platform old school, but with a really smart adjuvant . So both Valneva, and I think covaxin. Look like, you know, if I, if I had favorites, those would be it. And, and we can predict, you know, we understand how these work a little bit better than some of these nucleic acid delivery platforms, which might work, you know, maybe in different age groups where, you know, the thing is the traditional platforms with these adjuvants, they actually use up a lot of your resources.

Like they induce what we call myelopoiesis. There's a large amount of immune mobilization and energy that occurs. You get a bit of fever. So that's really good for if you're young and healthy and have those resources, perhaps if you're frailer and older, maybe you don't want. Elicits a strong immune mobilization and maybe that's where the, the marinade based vaccines, but you don't stimulate that kind of, oh, whole immune activation would, would work as you know, I can, I can see that in older people, they might not have the resources in their body to, to go all out like that.

But for young people, it's a lot better for your, I think for, for activating an antiviral response.

[01:11:26] **Hirad:** So it sounds like we could have a multi-pronged approach where you know, we have these mRNA vaccines that elicit a bit of a weaker response and we can give those to the people that are more, would be more vulnerable and we could have would it be actually be an sterilizing immunity for, with these other vaccines that are coming down for for the rest of the population?

[01:11:45] **Shirin:** Yeah. So the evidence of that is, is not known. My prediction would be no. And primarily is because we're injecting it. I think when we take an intra-nasal like live attenuated, like the flu mist, that would be more sterilizing because the route of administration you need to like have IGA and all these sort of mucosal, immunity, prime to neutralize where the virus enters and replicates. That's where the viral viral load is really high. Anytime you're injecting things for a respiratory infection, I think will not give you optimal sterilizing immunity for where at least very that's very long lived. And so I think, you know, if you were, if you were smart and had a strategy and saying, oh, you know, when we have a respiratory virus, this is the type of vaccine we should be making, you know, we should have that in house.

I think one of the problems with Canada, we don't have any money. We're very much reliant for other people to produce our stuff. You know, we're not using our, the knowledge base that we have. It's not very strategic. So if that's why I think if Canada sort of invested in its own, for things that are critical for, you know, life and death, things, we should have our own manufacturing. We should have scientists who know what's the best type of vaccine should be.

You know, it's not rocket science. Anyone can think about it. So they go, of course, we were on a live attenuated intra-nasal vaccine and we have enough of our, you know, we can it's for gene therapy. We have the technology now, especially with CRISPR and all these other tools where we can. You make attenuated vaccines a lot easier instead of like doing it the old school way.

We can really expedite that if that's where we wanted to put our resources and I'm thinking, it makes sense I think overall we're with our population increasing, we can see that this is becoming, you know, I think economically it might make more sense now, especially when we're seeing infectious threats again, you know, sort of put a halt on globally economic activity that may be, they'll say, oh, you know, it might make sense to invest in this at this time.

And you know, Canada is positioned to do that if that's where we wish to put our energy.

[01:14:01] **Hirad:** Yeah, well, hopefully, by the time the next pandemic rolls around, we'll have some capacity to respond to it a little bit in house.

[01:14:09] **Shirin:** Yeah. I think the problem really is , you know, coming from both academia and industry in Canada, one of the frustrating things is like one is the investment concept. They're, you know, they need to incentivize investment into the biotech community like they do with the fossil fuel industries or, or mining where they have flow through shares and stuff that they make it really attractive to invest in it.

And we don't do that for, for these more knowledge type of economies. The other problem is, is that all government programs are so short-lived. you have to be at the right time at the right place. There's no long-term because as soon as the government changes, then the priorities changes and it goes away.

You need to invest for a long-term in this, in these sorts of sectors. We're very well positioned because of the expertise. You know, we have people who go to university for a long period of time. We have. All that stuff. What we don't have is the ecosystem. Like we, there is in for example, Silicon valley or in the Boston area there, they've really built a really, a thriving ecosystem for, for tech and biotech.

And and I think that's where the future, especially now listening to, you know, the, the climate change meetings and everything, we can't be reliant on bitumen for the restaurant for, for, you know, the basis of our economy. And if we put that $14 billion, that meant to that trans mountain pipeline into something like the biotech sector and manufacturing biopharmaceuticals we would be so much better off and better positioned moving forward for the future economy.

But I'm biased. Obviously. I will say that.

[01:15:54] **Hirad:** Yeah. Trish. Do you have any other questions? 

[01:15:56] **Trish:** I learned so much today. This was so interesting talking with you. I, you know, it's always just such a treat to be able to speak with such a careful thinker. And I, I feel like I'm excited already to go back and listen to it again and really try and absorb because it was it was a lot of information and thank you so much. It was so educational.

[01:16:15] **Shirin:** I think what you guys are doing is great, like going out and really speaking about things that you're interesting and that's, that's the joy of life. Isn't it.

[01:16:24] **Hirad:** That's the plan. Yeah, that's what we started this. Yeah. Listen, thanks so much for taking the time. I really enjoyed this and hopefully it'll make a little bit of a dent, one can hope, into into bringing a little bit of perspective to more people, especially in Canada.

Cause I feel like you know, a lot of people here have. Lost the plot on what's important and what's actually going on. So yeah, really appreciate you taking the time to to speaking with us.

[01:16:50] **Shirin:** no, it was a pleasure. And I love the fact that people are having open discussions and having other thoughts about what's happening and different narratives, because I think having different perspectives is so critical and we can't be putting ourselves into a little, a rabbit hole and not looking at the big picture.

And I think, you know, it's kudos to you for bringing out thinking about all these different aspects and, and bringing out different perspectives. So, thank you.

[01:17:20] **Hirad:** 

So listeners, if you want to pause the episode at this point and take a little breather, this would be a good point. Having just talked to Dr. Kalyan for the last little bit, there was a lot to process there and for the next little bit Trish, and I will just have a little bit of a debrief. 

[01:17:35] **Trish:** Yeah, congratulations to making it through all that.

That was a lot of information, but Dr. Kalyan just knows her stuff and it was really, she packed a lot into that. 

[01:17:46] **Hirad:** Yeah. So what'd you think, what grabbed your attention more than anything else? 

[01:17:51] **Trish:** Well, there was a lot there that I wish that we could just spend another hour going through everything she talked about, but I think we're going to try and keep it short.

One of the biggest things that stuck out to me was that basically I had been treating this mRNA vaccine in my head. The same way. I had thought of previous vaccines in that when I get a tetanus vaccine, that means that I'm not going to get tetanus in the future. And it seems like these MRN vaccines are very useful in that they keep people from getting really sick, but they don't necessarily prevent you from getting sick at all.

So I kind of like in my head have reframed cOVID in that probably we should all expect to get COVID at some point, whether we're vaccinated or not. And this is okay because these vaccines will keep us from getting really sick and ending up in the hospital. And hopefully it'll just be a little low level thing.

So I think that this fear and kind of wanting to. Avoid COVID at all costs and you know, don't go to any weddings. Don't see any friends, they really locked down. I don't think that that's a useful mentality. And I think that we need to say like, it's out there, we're probably going to get it. But if you're vaccinated, you're fine.

And so, yeah, it just, it was a little bit of a mental, my mindset has shifted a bit. 

[01:19:15] **Hirad:** Yeah, I think that's a really good point. And that's, I think one of the main things that I feel like our public health and public communication on this , has been lacking on, like we talked about in the, in the discussion with Dr. Kalyan, this thing is not going away. The prospect of getting to COVID zero is off the table at this point. So. You are going to be exposed to it. You're probably going to be exposed to it multiple times in your lifetime. Just like when you're exposed to the flu virus every year. And that's fine for most of us, that'll be okay.

And with the. Vaccines that we have, which is actually a bit of a misnomer. I don't think given how we know they work at this point, we can't really call them vaccines because they do that word kind of sets a certain expectation, 

[01:20:00] **Trish:** it's true it's true, 

[01:20:01] **Hirad:** which these ones don't really fulfill. 

[01:20:03] **Trish:** They are a little bit of a different tool kit.

It's like a little different tool in our toolbox and the vaccine. That's a very good point to make.

[01:20:09] **Hirad:** And they do confer protection. And so having been vaccinated, you're probably better equipped to get infected by COVID, which you will. Again, it's just a matter of when, not a matter of if, but yeah, I think we need to be a lot more honest about that reality on the ground.

And I think a lot of people. Because of the way that we have responded to this virus, which again, made sense in March of 2020, when you didn't know what you were dealing with, but we know what we're dealing with now. But because of that response, a lot of people are so petrified of this disease and like, like Dr.Kalyan said the reality of the risk doesn't fit the terror that a lot of people are feeling. 

[01:20:49] **Trish:** The fear is mismatched. 

[01:20:50] **Hirad:** Exactly. 

[01:20:51] **Trish:** No, I think, I think that's true. And I think that, you know, people should try and get back to things that are healthy and make life fulfilling and not sit home just in fear and crippling anxiety.

That would be a good segue sort of talking about the fear of mismatch into these mandates. 

[01:21:13] **Hirad:** Right. So the mandates are where I get quite worked up about what we're doing. So in, in my mind, these vaccines, they are experimental treatments. There is a lot of good reason to be concerned. And this is again, one of those reasons we were recording this debrief a few days after having talked to Dr. Kalyan.

In that time Taiwan has taken the Pfizer vaccine. They've removed the second dose for children, age 12 to 17 because of the risks of myocarditis and pericarditis that they, that they pose. And so it's like the longer you wait, the more you're learning about it. And we are learning about these side effects.

We learned about after millions of people got these vaccines, we didn't know what they, what these side effects were. Right. So to me, when people are concerned about it, that's a very legitimate concern when they think that, okay, this was an emergency use authorization. We don't know the long-term effects.

They are correct. Now in a situation where 87% of the people were willing to voluntarily take this up, spending our political capital on. Coercing the remaining 13% to get that vaccine to me seems like a very, very foolish expenditure and it's just breeds mistrust. And I think justifiably so. 

[01:22:42] **Trish:** In an earlier conversation, you put it away. I really liked is this how we want to be expending political capital to sort of like, what is the goal of all that? Is it going to make a huge difference? Epidemiologically? If we get that last, I think now it's even like less than 10% of vaccinated is a really good point.

And just to be clear, because I feel like as much as we trying to be very clear with what we are saying, I think it's also worth being really clear saying what we're not saying. I don't think that we are anti mandates as a matter of principle.

[01:23:14] **Hirad:** Right. Yeah, so I had this conversation with a few friends when the mandates first came out and one of my friends asked a really good question, which is okay if you're against these than under what situation would you be for a mandate?

And there is the point is that there is a situation where mandates would make sense. You can't just make a blanket statement that the no, the government should at no point be able to mandate something like this. Right. And they're at the, if you imagine a graph where one axis is severity of illness and other axis is effectiveness of the cure, there's probably a line on that graph past, which it absolutely makes sense to to mandate vaccines or any kind of medical procedure and below which it does not. The reality of this virus is we are far on the, kind of the lower end of both of those measures. So I heard historian Neil Ferguson talk on a podcast with Bari Weiss, where he was making the point that if you look at the death toll from this pandemic and compare it to the pandemics that we know about, historically, it doesn't even rank in the top 10, right?

This is a very mild pandemic. Whereas if you look at the economic impact from our response to it, it's right up there with the great depression. So our response to this has been quite disproportionate and. We kind of keep doubling down. One of the reasons why I thought it was really important for us to have this conversation is because I think in Canada uniquely we're in a situation where if you hear, if you see, for example, on Twitter, hashtag trending, that wants to see that is calling for say fire Bonnie henry.

The reason for that hashtag is like completely the opposite of the American response. If we're calling for our public health officials to be fired is because they haven't put enough restrictions in, or they have lifted restrictions too fast. So the Canadian public for whatever reason seems to be clamoring for more and more measures.

And. That's to me, that's really disturbing. I don't know how we got here. There seems to be a lot of terror, like we talked about and people just want to keep doubling down on these measures. That really there's. They're uncalled for. 

[01:25:26] **Trish:** Yeah. I don't think that there's good evidence that they would accomplish what people think they would accomplish.

I think that people think that if you keep locking down harder and harder, you're going to get to COVID zero and guys like that. I hope we put that to rest. Like that's a pipe dream. It's never going to happen. It's here to stay. We need to reframe how we think of this. It's you're going to get COVID, but like, we've got some good tools in our tool kit now, so that it doesn't kill you.

I'm like, that's a really good thing. 

[01:25:55] **Hirad:** Yeah. And to be clear, also there is that age discrepancy as well. So some people are more at risk than others. So I think, I think it's, it's one of those situations where there is a problem. There is no great solution here, right? But it's really hard for people to admit that when we have a problem, we don't actually have a great solution.

That's the reality. Sometimes that you have a problem and you don't actually have a great solution to it. And this is one of those times. So Dr. Kalyan mentioned some other tools that we can use to diversify our portfolio of responding to COVID those tools. It'd be nice if there were around, they're not around at the moment, but that doesn't mean you just grab anything and try to throw it at the, at the problem and it's going to go away. It doesn't necessarily do anything.. 

[01:26:38] **Trish:** And I think that this is like another important thing too, is because, you know, pushing through experimental treatments and like these is it nucleic delivery devices. Is that the term she used for these mRNA vaccines? I think that these have been. The lifesaver in the early days of this pandemic when it was going crazy. But like now we, we have a lot more data. We understand a lot more things about this disease and we know a lot more about these vaccines saying that you, we should take a minute and look at the science before we proceed with, you know, like a lot of boosters or like giving it to every kid in the world.

That doesn't make you like anti-vax, that's just saying that we should always be pushing the bar towards safer and like that should, that should just always be the way that we are trending. It's like we have something that's pretty good, but that doesn't mean we can't make something better. We can't make something safer.

We don't need to get political. Where we start like crucifying people for being like, this is kind of experimental and there's all sorts of weird side effects, cropping up. And like, maybe we're not comfortable with this. Like we can all just be rational. I think. 

[01:27:45] **Hirad:** Yeah. Especially with vaccinating children, this is just bonkers to me.

If our goal is to make sure we reduce the loads in hospitals. Vaccinating children is not going to be the thing that gets us there. That's not the solution. We know that vaccines don't really help transmission. they are still experimental. They're still in the early days. And children just don't have the risk to warrant giving them a medical procedure whose side effects and long-term effects we don't really understand.

[01:28:14] **Trish:** Yeah, I think we have enough breathing room here to kind of look at some of these. You know, side effects and look at who's being hospitalized. we can be more targeted a big thing that I just. Took from this as well. And this is a lot of the stuff that we have talked about with some of the books we've read is just wanting public policy that is science-based and data-driven. And I feel like it's more about a narrative now of like showing your, like with the good guys to like, get at saying, you'd get as many boosters as you possibly need. Like, this is, this is me, like getting a little bit contrarian. I'm not even against boosters or anything, but I just.

I want data to be presented in a way that's clear and honest and not presented in a way that trying to get you to do something to fall in line with a narrative. Okay. A good example of this is as I was just looking on the CDC website, but they were saying if the risks of dying were. From COVID and the way that they presented it, I thought was really annoying because, oh, sorry, it wasn't even dying.

It was just hospitalization and death by age and the way they present it. So 18 to 29 is like the reference group. And instead of saying, it's like, oh, there's this like percentage of the population that gets it and ends up being hospitalized. It has, whether you are one time, two times, four times, 200 times more likely to be hospitalized than an 18 to 29 year old.

And this was exactly what Dr Kalyan was talking about, which is relative risk versus actual risk. Like, I feel like this is presented in a way that looks scary. So if you say you're like 40 to 49, they say you're 10 times more likely to die from COVID than an 18 to 29 year old. Like that sounds much scarier, but I think that it's not necessarily a good way to represent risk.

[01:30:06] **Hirad:** Yeah, I think, well, I mean in this situation it could be that if the, if the risk to 18 to 29 year olds is really, really low, then a big number multiplied by a really small number. That could be anywhere. Right? 

[01:30:18] **Trish:** Well, that's what I mean. Like, so if you're at like 0.0, 1% risk of dying 10 times, that would be like, 0.1, right?

These are things that frustrate me. And I would like to see better transparency on like how data is collected what's in that data sets. Science should be completely nonpartisan and just truth seeking. 

[01:30:39] **Hirad:** That's the thing that really grinds my gears is when there we've got two political sides that are, I mean, Canada really, we don't have two political sides.

We always only have one political side for the most part, but there is a narrative and it's not just that it's a narrative, which is bad enough is that it pretends that it's a science-based narrative, which it is not. And that's one of the things that I wanted to clear up with this episode, the science we have, if you read the papers that are coming out on this subject.

If you look at the data that people are collecting. It does not warrant the public policy that pretends to be science-based. And I hope we can got that across. 

[01:31:18] **Trish:** They were never clear with what the ends were. You know what I mean? It's like we put in a big two-week quarantine for people entering the country.

I would've liked to have seen something that they're like, oh, well, if we model it, we think we're going to keep this much COVID out or whatever. Or does that even not matter, because it turns out the vast majority of people are coming in for like essential reasons, which was the case. It didn't keep the Delta variant out.

It didn't keep COVID out. A lot of this stuff to me, seemed like an incredible waste of money, really inconvenient for, you know, families who are separated. 

[01:31:52] **Hirad:** Yeah I think some of our policies right now are definitely, I mean, you're right. The quarantine hotels were,

[01:31:59] **Trish:** I mean, that's the easiest one to pick on because it was so obviously ridiculous.

[01:32:03] **Hirad:** Yeah. But even some of the ones right now. So at the same time that these vaccine mandates came into effect in British Columbia we also had a renewed mask mandate. So early in the pandemic, we had a mask mandate for public spaces and then it was removed and then it got reinstated at the latest wave and.

Early on. It kind of made sense because we were supposed to be masking up indoors and...

[01:32:28] **Trish:** we know it's airborne. 

[01:32:29] **Hirad:** We know it's airborne, we're supposed to wear masks to prevent it. And at that time we're also supposed to keep distance. So a lot of indoor spaces like restaurants and cafes were running at 50% capacity where the tables were supposed to be certain distance from each other.

With these latest rules, there is no distance. So I can go to a restaurant. I can sit elbow to elbow, and I have done this with other patrons that are there. And the minute I stand up from my chair, I have to put a mask on as long as I'm sitting. It's okay. But a minute I stand up, I have to put a mask on.

And so this is. You know, there's pictures of, you know, back in the medieval times when the black plague was ravaging through Europe and they had these quote unquote doctors that were wearing a bird costumes, and they were meant to keep the Juju away. That's what masks are for us right now, because they're not, we're not using them in any way that would be remotely effective.

[01:33:27] **Trish:** At least not on airplanes and in restaurants and stuff.

[01:33:31] **Hirad:** Yeah. I mean, it's not that masks wouldn't work. Yeah. 

[01:33:35] **Trish:** You have to use them properly. 

[01:33:36] **Hirad:** Yeah. The rules we're setting, they're not meant to actually prevent transmission of the virus. Right. And, and I mean to kind of go back to the point of people are just afraid of this and they're kind of throwing anything.

They can add it. We're still kind of going through this like security theatre of sanitizing, everything, which I'm not against, you know, sanitize it. It's probably better if it's clean theater, theater. Yeah. Again, like we learned this months ago that this thing was airborne. Right. And if we want it to make some real difference, we would be the government. We should be subsidizing restaurants to fix their ventilation and filtration systems.

[01:34:16] **Trish:** Such a good point. Yeah. So is there anything else you wanted to add? I mean, there was so much to talk about there. I wish we could have a bigger debrief. I learned a ton about how vaccines work and the human immune system.

[01:34:30] **Hirad:** Yeah, I think it was super interesting. And listeners, I hope you took away as much from this conversation as we did. This is a rapidly evolving situation. Hopefully no pun intended. I'm sure we're going to come back to this and maybe do another episode. The current vaccine passports are supposed to be up for renewal at the end of January.

I believe. They're kind of indefinitely subject to renewal. So there's really no clear end dates. So we'll see where we are then. 

[01:34:58] **Trish:** And hopefully Bonnie Henry doesn't close any ski Hills on us this year. All right. Thanks listeners. We'll talk soon. 

[01:35:05] **Hirad:** Bye-bye.