Craig Laferrière head of vaccine development for Novateur Ventures, joins Neil to discuss the relative strengths and weaknesses of the different COVID-19 vaccines in use and in development.

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Full Transcript

Danny Levine (Producer).

Today. We're going to talk about COVID vaccines with our guests, Craig Laferrière. I know you've been looking forward to this discussion who is Craig?

Neil Littman (Host)
Yeah, so I am incredibly excited to have Craig on the show today. I've been wanting to do a deep dive on the, the vaccine landscape for a while now. So Craig is an accomplished medical adviser. He has expertise in vaccine design and manufacturing. He's got over 25 years in experience in regulatory clinical research access marketing. He currently is head of vaccine development at Nova terror. He was a medical advisor to the vaccine division at Pfizer in Canada. He was part of the vaccine leadership. He was part of the vaccine leadership team there. So he's got a ton of experience. He was previously at GlaxoSmithKline as well. It brings out a host of experience and knowledge from his career in vaccine development. Really excited to do a deep dive with him today.

Danny Levine (Producer)
There's been remarkable speed and vaccine development in response to the pandemic and a wide range of technologies that have been employed deployed. What do you think the response has said about the industry?

Neil Littman (Host)
I think it said a lot about the industry in terms of the industry's ability to collaborate and work together at a, here to, for unprecedented scale. So, the, the development in terms of bringing new vaccine to market was I think, accurately termed, operation warp speed. I think the industry really did deliver on that moniker. I think the vaccines have been developed at warp speed. Things that would nor to nearly take years of development were really proven and born out in, less than a year's period of time to combat this global pandemic. I'm really excited to talk to Craig and understand some of the history. What has, what has laid the groundwork to allow the industry to move at this fast pace? What are some of the technologies that are being deployed out there to develop vaccines? There there's at least four different types of technologies being employed to develop vaccines where, what are those, how are they different?

Neil Littman (Host)
How do they work? How should people think about the different types of vaccines? Are there differences that people should think about? I think Craig will bring a really unique perspective.

Danny Levine (Producer)
Well, if you're all set,

Neil Littman (Host)
I'm all set. Let's do it. Danny. Greg, thank you for joining us on the show today. I'm incredibly excited to welcome you.

Craig Laferrière (Guest)
Thank you. I'd say we're pleasure to be here now.

Neil Littman (Host)
Craig, today, we're going to talk about the COVID vaccines, the different technologies being deployed, the recent paper you co-authored in the open access journal viruses that looks at how the different vaccines compare. Two things that I think surprised most people about the COVID 19 response was number one, how rapidly the industry was able to develop and win approval for several different vaccines. To me, what was even more surprising was the range of technologies that have been deployed. The pace at which industry has been able to move has been impressive. I think by most measures and surpassed, even the expectations held by most industry folks, as well as the general public. How successful have the vaccine development efforts been? Why do you think we've been able to see vaccines come online as fast as they have?

Craig Laferrière (Guest)
That's a really good question. The, I think people don't realize that a lot of research was being done already on these Corona viruses, because of course there was the SARS epidemic, which was, I forget what year it was 2008 and 2007, maybe. Also there was Merz more around 2015. I have to, I have to correct me on there that the years for those outbreaks, but it was known that these Corona viruses had the ability to infect humans. There was already a lot of base line research being done on what are the best antigens to pick for the vaccine, how to manufacture those antigens. When SARS cov two came along, I think the, all the groundwork had been done. It was just a matter of cloning, the actual gene for this particular virus, which was, as you may know, it's the, the spike protein, which is, three out of the four vaccine platform technologies use that spike protein as their main antigen.

Craig Laferrière (Guest)
It was a question of getting the manufacturing up and running and running the clinical trials. So, so it wasn't as if were starting from zero, there was a good baseline already.

Neil Littman (Host)
And, and so Craig, do you think all the work that had been done previously on the Corona viruses that were related to the SARS outbreak, the murders outbreak, identified that the spike protein was the right antigen and the right target to go after? Because I think early on that was of a gamble, right? A lot of vaccine developers were all going after the spike protein, but it wasn't yet proven at that time that was actually the right target to go after.

Craig Laferrière (Guest)
Yeah. I mean, they all, a lot of the clinical work of course had, they hadn't gone into phase three. There had been some, phase one studies just to look at immunogenicity and one of the things that was done, and this is maybe getting technical, but there w it was known that the protein has a trigger mechanism in it, and that it the pre fusion and post fusion in it. The protein changes shape when it tries to fuse with the surface of a cell. There had been some concern in the past that during the manufacturing process on this of this protein, it could, the trigger could spring and the shape of the protein would be in the post fusion shape. In which case you wouldn't get a very useful immune response. They had already done some research on making some amino acid modifications in the spike protein that locked it into the pre fusion shape, the Prefuse and confirmation.

Craig Laferrière (Guest)
That, that particular piece of technology was, had been re studied very well. It was, the animal models were also there to show that this antigen in this particular shape did provide protection against Corona virus infection.

Neil Littman (Host)
And Craig in June of 2020. About a year ago, you publish an article about what the ideal vaccine would look like. You looked at what the ideal target product profile or industry jargon, TPP would look like, what did you come up with at that time?

Craig Laferrière (Guest)
Well, that's, I'll have to dig out the paper and take a look at it, but, the most, this is the target product profile is a technique that's used by all pharmaceutical companies. And, and probably also even a lot of other industries where they try to have input into the, what the product is going to look like to satisfy the market. With it in early on in the whole development process, the idea is that the scientists are aware, okay, this is what we've got to develop. The clinical researchers know this is the kind of study we have to perform in order to get the evidence that we can talk about our product and say, yes, this product protects, people against this disease. The, the main thing that was a very interesting in these target product profile was the efficacy requirement and the, the, usually the, when you're getting a license for a vaccine, you have to show that the, of course you have like a percentage efficacy that's calculated.

Craig Laferrière (Guest)
There's a statistical analysis that you've got a confidence interval. So let's say the vaccine is 70%. Your clinical study shows the vaccine efficacy is 70%, but due to statistics, there'll be a range. It could be anywhere between, 30 and 90. One of the things that came out in the TPP is that the, especially the FDA said that they want to be lower limit of efficacy to be 30%. Usually that lower limit is actually 0%, as long as you can show that it's somewhere above zero, that the vaccine is providing protection, then that's sufficient for getting a license. In this instance, they wanted the vaccine to have a 50% efficacy and had a lower bound of 30% efficacy. That set some criteria around the types of clinical trials that could be done in order to prove that, and, it made the size. Of course the, each manufacturer used a power calculation to show how statistically, how large the trial needed to be able to, to prove that.

Craig Laferrière (Guest)
And, and one of the things that came out at that time also, which was very interesting, you rarely see if ever is that almost all the manufacturers published their clinical trial protocols online. They showed how they were going to do this trial to show that the vaccine had efficacy. That's unheard of, usually these clinical trial protocols are kept very secret. And, and the statistical methods that they use are, not put on display until after the, the trial is completed and the study is published. It was really unprecedented to see that all of them took this particular target product profile of the vaccine efficacy of 50% with a lower bound of 30% into their clinical trial studies.

Neil Littman (Host)
So, Craig, there's a few things I'd like to dive into there. Number one, any insights into why the FDA would have this increased requirement in terms of the lower bound of the comfort's confidence interval being 30%, as opposed to what's typically 0%. Why would the FDA want to see that in this, in this instance?

Craig Laferrière (Guest)
Yeah. It, what, I don't have any insight on that. I, I spoke to my brother-in-law was a biostatistician and in fact, he was asking me, w why are they doing that? And, and don't have a straightforward answered for you on that one. Sorry.

Neil Littman (Host)
Okay. Yeah, no problem. Of course, as we know, the efficacy that we saw in the phase three clinical trials was well north of what the FDA had had set, right. We were in a 95% range in terms of efficacy. What we'll dive into that, I guess the other point I wanted to ask about was you had mentioned that publishing the clinical protocols was really unprecedented. I mean, that's usually pretty, I guess, confidential within the pharmaceutical companies. Do you think that was a result of public pressure or just how public this global pandemic has been? Well, why do you think the companies decided to pursue that unprecedented path?

Craig Laferrière (Guest)
I think that already by last summer, when, there was this very rapid preclinical development, the animal models, the manufacturing, and then the already the move into first in humans. I think there was already, the anti vaccine groups were talking about this development is happening too fast. I think it was a response to that. I think it was a recognition that this whole process, if it's going to go fast, it needs to be completely transparent. And, and I think that part of it was this opening up and putting the cards on the table, so to speak so that everyone could see exactly how things were proceeding.

Neil Littman (Host)
For the new study. You looked at a dozen vaccines that were in phase three that were phase three ready or later in development. As of November of this year, there were four basic technologies used by these vaccines. I really want to dive into each of these. I thought we could walk through each one and how, and have you explain how they work. The first are the messenger RNA vaccines, which include Moderna and Pfizer beyond techs approved vaccines. Those were the first approved vaccines. Could we spend a little time? Can you explain how those MRR vaccines work?

Craig Laferrière (Guest)
Yeah. This is a really exciting technology to me. I had touched on it back in the nineties and had completely forgotten about it. And, and so when it came out in the spring that this was a technology that was in the running, I was really excited. I read up all the patents and I read as much literature about it as I could. Just to get catch up on 20 years of research that had been going on since then. The idea is that interestingly enough, the very first person to use this idea was a guy named Giorgio Dimitri at us back in 1978. He found that if you take a little piece of messenger RNA and you, and envelop it in a, a little fat droplet that it'll be taken up by cells and that those cells will express that whatever that messenger RNA is coding for and produce that protein.

Craig Laferrière (Guest)
There'll be an immune response against that protein. Oddly enough, that whole idea remained dormant for many years until it was picked up again, later the, in the the early nineties, an idea came along to either just directly inject DNA or directly inject messenger RNA into animals. It started off with animals and mice. And, and what was found is that would elicit an immune response against the protein that the messenger RNA or that the DNA coded for. There was a lot of excitement about this technology, but when it was tried in, in primates and in humans, it didn't work. What was going on was that there are enzymes in our blood that simply digest the DNA and RNA before it has a chance to be taken in by a cell and have its code translated into a protein. So, so the trick was then, well, how do you prevent the messenger RNA from being digested?

Craig Laferrière (Guest)
This is where this little lipid droplet came back. A lot of the technologies is involved around getting this little fat droplet to coalesce around the messenger RNA, and then that protects it. You inject it into an arm, it doesn't get digested by the enzymes that are in your blood. That little droplet is the right size. It's small enough that it gets taken up by yourselves. So they're very tiny. They're about 80 nanometers in diameter. So that's why they're called lipid nanoparticles. The other trick was that once it's taken up by the cell, now, the lipid has to release that messenger RNA into the cytoplasm of the cell. That's done with the technology they call these positively charged lipids or cat ions. And, and so there's a whole series of patents around those particular positively charged lipids that their action occurs when there's a change of pH.

Craig Laferrière (Guest)
When, when a cell phone when it eats up a little droplet, it goes into something called an endosome and then that end zone, there are N enzymes that are put in there to digest whatever that is in that particle well, that chain, and there's also a change in the pH inside that endosome. When that pH changes, that triggers the release of the messenger RNA, and then the messenger RNA is able to escape into the cytosol. It's just recognized as a, a regular piece of RNA. The other trick that they did was to make sure that there was no way that the cell would think that this piece of messenger RNA is foreign. It would think that this is just a regular old piece of messenger RNA, and it would, the machinery inside the cell would take it and translate it into the code, into whatever protein that it coded for.

Craig Laferrière (Guest)
Of course, in this case, it coded for the spike protein. Now that's recognized as something foreign that triggers the whole immune response and, and away you go.

Neil Littman (Host)
So, Craig, I think similar to your earlier comment about, how the industry was able to advance these vaccines at such a rapid pace, because there had been decades of work done on, Corona viruses. Yeah. I think similar there's, as you mentioned, there's been decades of work being done for Emma M RNA vaccines. This was I guess, the coming out party for, these types of vaccines, this technology to a large degree, obviously these were the first MRNs and M RNA vaccines ever approved. I think what was really incredible to me was the pace of development. I might not have my timeline exactly. Right. But, you know, Madonna for example, right. I think Chinese researchers first published the genetic code of SARS cov two online and then within, I think it was like 48 hours of that being published online. I think Madonna was able to print their MRN, a vaccine from the digital copy of the genetic code without ever having a physical copy of the virus.

Neil Littman (Host)
It's that actual MRI and a vaccine, which is, has been the approved vaccine that is now being delivered to millions of people. It was just incredible in terms of the turnaround time and then going from a, the digital world to the physical world. That's now the vaccine that is being distributed. Of course it was the clinical trials that took much longer to complete, but that was pretty incredible to me. I don't, I don't know if you had any insight into that in particular.

Craig Laferrière (Guest)
Well, it's one of the great things about this messenger RNA technology is that it's a lot of it is just chemistry. You're not, you don't need to use living cells to manufacture it most other. In fact, all the other vaccines require living cells to produce either the virus for the viral vector types of vaccines or the subunit protein types, or even the whole virus vaccines, those require living cells. You have to grow those in a bio fermentor and they have growing conditions and have to be kept at a certain temperature, a certain amount of oxygen and so on. Whereas the, what what's going on with the messenger RNA is it's almost purely chemical and you just mix the reagents like you do in a test tube and a way the reaction goes. These things are much easier to control much easier to purify. Right now they're more expensive because the reagents are all there.

Craig Laferrière (Guest)
There's a whole industry that needs to be built up behind all of these different reagents that needed to be added. But I think that'll change. I think the price of these types of vaccines will come down. When more of the industry gets behind this manufacturing platform,

Neil Littman (Host)
I think this is a nice segue into the second bucket of vaccines that are being developed. These are viral vector based vaccines, which among others include AstraZeneca and Johnson's vaccines. Can you describe about what these are and how they work?

Craig Laferrière (Guest)
The viral vector vaccines are all based on an adenovirus virus vaccine that is non replicating, and that's the real secret behind this vaccine that makes it safer than other types of live virus vaccines, which can replicate. For example, the measles mumps rubella vaccine that childrens get is it's an attenuated live virus. Those kinds of vaccines should not be given to people with damaged immune systems because they might not be able to control the virus, even though it's weakened, it could get out of control. With these viral vector types, the identical virus is modified in such a way that it is in enable of replicating. I'll give you of an explanation of how that's done. It's all based on a cell line known as the HEC 2 93 cell line. This cell line was an invented by a physician named Frank Graham back in the 1970s.

Craig Laferrière (Guest)
Up to, at that point, there was a lot of interest in cell lines that is types of cells that can grow outside a living body. The first cell line that had been discovered was the, it was created it's, it's a very interesting story. There's a, there's a book about it called the immortal life of Henrietta lacks. What was found was that sell herself, she had a, a cervical cancer, and that cells from that cervical cancer could be put in a Petri dish and they would just continue growing. Now, if you take any other cells from your body and put them in a Petri dish, they'll grow for a week, maybe two weeks, but eventually they'll die, but these particular cells just kept on multiplying. It kept on growing. There was a lot of interest in creating these kinds of cell lines. It's a very interesting, it's somewhat controversial for this heck cell line because the HEC stands for human embryonic kidney.

Craig Laferrière (Guest)
There's, you might've heard some chatter on the internet about people shouldn't receive this vaccine because it's based on a human cell line. I think the Vatican made a response to that and that it was perfectly morally acceptable to use this vaccine. I think that should help allay some of the moral concerns that people have, and the laws have improved since the 1970s on who controls your cells and what they can be used for, but they didn't understand how a cell could be made immortal. Back in the seventies, Frank Graham was doing what a lot of other physicians were doing, and that was mixing cells from animal source or in this case, it was a human kidney mixing them with viral DNA. The viral DNA that he was using was on a dental virus. He would put these cells in a Petri dish, and most of the cells would die by 10 or 15 days or so, but some of the cells continued on living and they, and so the culture, these cells, and it became an immortal cell line and known as the heck 2 93 cell line.

Craig Laferrière (Guest)
One of the interesting things about this particular cell line is that it produced some of the proteins that are part of the identity virus. Here's the trick is that you could produce an identity virus. You could remove some of those genes from the adenovirus, replaced them with a gene that was of interest to you. In this particular case for COVID the spike gene, and then you could grow those viruses in the HEC 2 93 cell line. The, the heck 2 93 cell would provide the missing parts of the lifecycle for the virus. The virus could replicate and continue to grow, and you could produce a lot of virus in that cell line, but those particular viruses, when coming into a healthy cell that does not have those additional genes, it won't replicate. It goes through one round. It will produce the protein in this case, the spike protein, and then that's the end of it.

Craig Laferrière (Guest)
The, the viral vector vaccines are, have a nice safety feature built into them. It gets the DNA inside the cell, but then it doesn't replicate any further than that.

Neil Littman (Host)
You, you had mentioned the book, the mortal life of Henrietta lacks, a fascinating read for our listeners who are interested in doing a deeper dive on the cell line. So, okay. That takes us through the first two types of vaccines, MRN, a viral vector based vaccine. I want to talk about a third type of vaccine that is in development. This is vaccines that are using recombinant proteins. These are developers such as Nova, for example, that are using this approach. Could you talk about what this approach is and how it's different from the other two?

Craig Laferrière (Guest)
This is technology that really came alive in the late eighties, early nineties, and is G genetic engineering at its best. The, it was, there were people were taking genes from viruses and so on and putting them in a bacteria like Ms. Shrieky Kolai and trying to grow them up. And these proteins didn't work for you. If you've made a vaccine out of them, they just didn't work. It was learned that the way it's not just producing a protein inside a cell, but there's a bunch of modifications that occur after the protein is produced. For example, there are some sugars that are added on to the protein, and there are certain environment that helps the protein get into the right shape. It was learned then that you could grow these, or you needed to grow these genes in other types of cells besides just bacteria. A lot of the different cell types that were used are the early, very early ones were yeast cells.

Craig Laferrière (Guest)
I think it's an insect virus cell line, or it's a, it's a virus insect cell that the gene is incorporated into four for Novavax. There's another company called Medicago in Quebec city. They actually use plant cells to produce these proteins and the second trick. Even when you got the protein with the right sugars on it, and so on, you still didn't get an immune response when you injected these things. They're actually, there are two additional tricks to making a good immune response. The second trick was that you had to get the proteins to form as if they are in the shape of a virus. These are called V LPs virus like particles, and you make some modifications to the protein so that they will assemble into kind of a small virus sized particle, again, the same size around 80 nanometers in diameter. Now immune system will recognize this as something that's foreign and you begin to get a good immune response against these small proteins.

Craig Laferrière (Guest)
The last trick that's needed of course, is that you tend to need strong adjutants. These are mixtures of, and it's really a, more of an art than a science of chemicals that will boost your immune response. The one from Novavax is called matrix M and M, and it has a additional immune stimulating properties that help again, to give a, a strong immune response against this recombinant protein.

Neil Littman (Host)
If I'm not mistaken, I think the Novavax cell line, I think they're actually using a, a moth cell line if I'm not mistaken. So, so, okay, fascinating. Let's talk about the last approach being used, which are inactivated viruses. This I believe is largely being used in efforts in China and India. Could you talk about this approach and how it works?

Craig Laferrière (Guest)
Yeah. So this is the oldest technology. There is, of course, this is dates from the days of Louie pastor, when you grew up the virus and then you inactivated it somehow. In the days of Louie pastor, that he simply let the virus dry out, but nowadays they use a chemical means. The, and so the, what is being injected into the person is the whole virus has grown, and then it's inactivated with chemicals. There may be an adjuvant with it. The, the Barat vaccine from India, they've added a special agiment that helps improve the immune response. It's it's the oldest technology. There is the only drawback from this kind of technology seems to be the yield and they are growing these viruses in a, I think it's an dog kidney cell line. Th we don't, we tried to do for our paper. We were going to do a, a cost analysis.

Craig Laferrière (Guest)
How much did it cost to manufacture these different vaccines on the different platforms? We didn't put it in the paper because we couldn't validate some of the numbers that we had, but by far, this technology seemed to be the most expensive. The reason being that the yields, at least from what was published that we had seen the yields were very low. You may make a huge bat of a batch of a vaccine, but only get, a few thousand doses out of it. So, so this technology is old and trusted, but it's it, it's the most expensive. The number we came up with was around a hundred dollars per dose. In fact, in China, we saw that was the going rate to purchase that particular vaccine was around a hundred dollars a dose. We're not exactly sure of those numbers as I say, but that would be the main drawback from that technology.

Craig Laferrière (Guest)
It seems to the numbers, they've announced seem to have reasonably good efficacy in the range of 50 to 60%, but, very costly to manufacture.

Neil Littman (Host)
Craig, let's dive into that last point about efficacy. For your paper, you consider five measures for your comparative analysis. The first of these was vaccine efficacy. What do we know about the comparative efficacy of these approaches? In particular, I'm also curious how do you compare the efficacy results across different vaccines and across different trials, many of which have used different statistical endpoints. Could you, could you talk about the comparative efficacy and the results that we've seen to date?

Craig Laferrière (Guest)
Yeah, that's a, it's a very good point. The making that direct comparison of course is impossible because they weren't all done in the same clinical trial. The, on the other hand, like I, as I mentioned earlier, the most of the companies have published their clinical trial protocols. You're actually able to see what is the end point of the, of the study. And, and most studies have very similar end points and that is, there usually is one or two symptoms, usually a respiratory symptom plus fever, but there's other ones also that aren't would be included. That's where the the small differences are, what are those actual symptoms? There's a PCR positive evidence of a viral infection, and that's a micro biological endpoint it's of course there may be minor differences in way that the way that PCR is done and the way the swabbing has done and so on, but for the most part in most studies, it's very, it's very similar that the end point is this really, microbiological proof that the person is infected with Corona virus.

Craig Laferrière (Guest)
So that makes them somewhat comparable. Although the information is not available for these inactivated virus type vaccines, I think we did find the protocol for one of the studies, but it was a, I think it was a Spanish translation from Brazil, but the other ones have their protocols online. And, and you can, if you want to get down to the, the brass tacks to see exactly how comparable are they are that can be done. We, we didn't actually do that. We just use the numbers that were quoted by the different public press releases, publications,

Neil Littman (Host)
Craig, as the new variants emerge, right, the efficacy from the initial trials has been really great. I mean, and you mentioned the paper, right? I mean, the MRA vaccines are the, 95% range. I think all of the vaccines are correct me if I'm wrong, but I think are almost a hundred percent efficacious in preventing severe disease, but as new variants emerge, do we know anything about the ability of these approaches to confer protection against, various emerging variants?

Craig Laferrière (Guest)
Yeah, that's a very good question. And there's two ways to approach that. One of them is to actually look at what's going on out there and what is known as an effectiveness study and in an effectiveness study, it's an epidemiological study where you have to have some kind of surveillance system, and you're looking at people who come into the hospital with the disease, and then you determine which variant they are infected with. You find out if they've been vaccinated or not. The country it's required that country has a very good vaccine registry so that you can find out exactly when they were immunized. And, and if they receive both shots, for example, so Israel, there was a study done in Israel with the Pfizer BioNTech and they looked at no, they didn't have the data on which variants were actually circulating or that people were actually infected with what they did have, but they did know that almost 80% of the variants of what was going on in Israel was the UK variant, the variant.

Craig Laferrière (Guest)
They were able to get a number, I think after one dose, it was between 47 and 65% efficacy. After two doses, around 90% efficacy. We know that the Pfizer Biointech vaccine has at least 90% efficacy or effectiveness against that particular variant. There was some data from the Novavax vaccine in South Africa, I believe it was a clinical trial and they showed quite high efficacy against the south African variant. On the other hand, similar data with the AstraZeneca vaccine in South Africa showed very poor efficacy against that variant. The, another, the new Brazil variant. The second way to look at the potential efficacy of vaccine is to do a virus neutralization assay. This is where you take a blood sample and you look at the ability of that blood sample to neutralize the virus. This is an assay that's done at a test tube. You have some cells growing in the bottom of the test tube.

Craig Laferrière (Guest)
You add the virus in, along with anti the antibodies from the person's Sera. Can that antisera stop the virus from infecting those cells inside the test tube. It's, it's what's called a correlate of protection. It's it hasn't been, I haven't seen any data published yet exactly on what the correlate of protection is for these vaccines. Any kind of indication from these blood tests would really be experimental at this point, but it does. It can give you an idea that if you change the variant of the virus, is, are the antibodies still able to neutralize it? Most of these tests are showing that you need a higher concentration of antibody to neutralize the variants, but still the variants can be neutralized. That's, that gives us some hope that these, these vaccines are going to provide this protection against these variants. I think only time will tell the it's of course the, the, the virus itself is to, in order to survive, if it needs to mutate, it will.

Craig Laferrière (Guest)
It's just natural selection in that any mutations that appear that are able to escape the vaccine. Well, those are the ones that will continue to survive and go on. It's going to be a, always a battle it's potentially, it's looking like it's going to be a battle between vaccines and virus as it has been with influenza for a long time. It might, who knows, it may end up that every year or every other year, we need a booster against the, a new variant that's circulating.

Neil Littman (Host)
I think in addition to the variants, right, the other key question is durability of response of vaccines, right? How long do neutralizing antibodies remain in the bloodstream? There any clear indication whether people need to be inoculated with a booster in six months or a year or two out from receiving their initial vaccination?

Craig Laferrière (Guest)
Well, of course these vaccines have only been immunized in people for less than a year now. You're, so the longest time you can actually look for a neutralizing antibody is only a year. I think this is, will be an ongoing research that, they'll look at what, how long does the neutralizing titer last? It's just a matter of time also to look at and see, is there an increase in breakthrough cases? One thing people forget is even with 95% efficacy, it still means that, 5% of people are going to have some kind of COVID case. If they, if they are exposed, this is why, of course, herd immunity is so important to, so you don't want people to be exposed, but at the present time with the virus still circulating about 5% of people are going to be susceptible and will. I think that will be tracked very closely to see how does the efficacy last with time?

Craig Laferrière (Guest)
Are we seeing more and more people who have been immunized coming in with an infection, and that will give an idea of the duration of protective efficacy with time. It's just the only way to learn that it's just to keep monitoring over time.

Neil Littman (Host)
Assuming that we will need boosters on a, let's say annual or fairly regular basis into the future, which I think seems to be the direction we're heading. If, if someone were to receive, an initial vaccine, let's say it was J and J vaccine initially, right. Which is the viral Bechtle based vaccine, could they receive a booster of a different type of vaccine? An MRI and a booster in the future. There any reason to think that they'd have to stick with the same type of vaccine that they were initially that was initially used?

Craig Laferrière (Guest)
Yeah, I've seen that. There's a lot of studies out there that are looking, studying that very question. Just off the top of my head, I would say that it looks pretty good that that will be possible. The reason is that at least three of these four technologies are based on the spike protein. If you've primed with one spike protein, you should be able to boost with another spike protein. I think the chances are pretty good that those studies will come up positive that you can mix and match at least the messenger RNA, viral vector and protein types of vaccines that are based on the spike, the inactivated virus ones, and not so sure that those ones that will be easy to mix and match.

Neil Littman (Host)
W we've obviously been battling this as a global pandemic, right? A good choice of a vaccine for the United States may not be as good a choice for India or Africa because of cost logistics or dosing, for example, how dependent are market considerations for choosing the best approach in various countries in various geographies?

Craig Laferrière (Guest)
Yeah, I think it's, it is a very important consideration and this is where these protein vaccines really, I think will they're, they've been longer to develop that they're coming in last, but they have the advantage of scale. They can produce much larger quantities per batch. They should, the interesting thing that ends up happening is that the, the production costs are so low, that it ends up being the glass vial that the vaccine has started, and that's the most expensive part of the vaccine. So, and the solution to that of course, has been to use multidose vials that helps bring the cost down. I think it is important that the, the that's an important consideration. I think we, the, I think everyone's like me is hoping that this is everyone in the world will have an opportunity to get a shot and from, and that's really the only way that will, will defeat this virus, because if it's, there's some population somewhere that is not vaccinated, then the virus is still has a foothold in the human population.

Craig Laferrière (Guest)
So, and, it's not just a co COVID, it's all vaccines. We need to reach every single child, every single adult and this way we all combined together and defeat these things.

Neil Littman (Host)
There, there have been some concerns about, equity on a global scale and the developed world getting, the higher tech vaccines and lower and middle income countries getting vaccines that may be, haven't been as well tested, or aren't maybe as effective. Do you think that's a valid concern?

Craig Laferrière (Guest)
No, I think it is. There is, I mean, I, I see it here, I'm in Canada and we've certainly seen the way the vaccine rollout has been done here, that, people with connections and learn and opportunities, and who are working from home have had much greater opportunity to be vaccinated than people who are working shift work. And, and can't take time off work because they'll lose their income. So, so there's inequities, even in Canada about who is getting access to the vaccines. And, and so th there was no doubt also that this is happening in other places. I was, we're seeing this now india. I was very surprised when the first wave india wasn't, they kept it under control, but now the second wave is it seems to be quite devastating to them. On the other hand, India has, is manufacturing. These vaccines, they have the AstraZeneca vaccine is being manufactured india.

Craig Laferrière (Guest)
They have the Barat, biotech is manufacturing. So, so in many ways, it's very encouraging that they have the technology within their own borders to actually provide the vaccine for themselves. In some ways the inequities are less than you might think. I think that it's something to be, hopeful for that and optimistic about that India does have the capacity. It's just, they've just got to ramp up and get all their people vaccinated.

Neil Littman (Host)
Craig, what, one final question from you, and this is from, the I guess patient point of view, does it matter what vaccine people get, right. If someone were to have the luxury of having a choice of which vaccine to take, should they care?

Craig Laferrière (Guest)
Well, that's a tough question. My attitude would be take the first one that you're offered. And, and I was fully prepared to take the AstraZeneca vaccine if that was the first one that was offered to me. On the other hand, I, I ended up getting offered the Pfizer Biointech and so I took that one and a 95% efficacy compared to 70% efficacy, that's, a substantial difference in efficacy there. So it does make a difference. If you have, if all things being equal, if you had a choice between Pfizer and versus AstraZeneca, I mean, I personally would pick the Pfizer, but if I didn't have a choice, if the government had purchased a lot of AstraZeneca and that's what was being offered to me, I would certainly take it. It's safe and efficacious and it's available.

Neil Littman (Host)
Yeah. Craig, I'm going reiterate your initial point there, strongly recommend that folks take whatever vaccine is offered and available as a first choice. I'm okay with that. Craig, I think we covered a lot of ground. I I'm really w was really happy to learn a lot more about each of the types of vaccines that have been developed that are out there being administered to literally millions of people around the world today. So, Craig, I would like to thank you so much for being on the show today and your time.

Craig Laferrière (Guest)
Well, thank you, Neil. It was a real pleasure speaking with you and I'm going to look forward to hearing more of your, your blogs and your online podcasts.

Neil Littman (Host)
All right. Wonderful. Thank you so much.

Danny Levine (Producer)
Well, now, what did you think?

Neil Littman (Host)
Yeah, I think that was a really great and wide ranging discussion. I, I was really thrilled to learn more about the different types of vaccines, how they work, how they compare. You heard us talk about the Mr and a vaccines harvest to do a deep dive on the, viral vector based vaccines, right? Those were AstraZeneca and J for example, the Novavax vaccine and others that are using the recombinant protein approach. The the more traditional vaccines that are using inactivated viruses that are really developed, being developed in China and India. I think it's really interesting to see not only the speed of the development of these vaccines, but the different types of technologies that are being employed, I think is also really fascinating.

Danny Levine (Producer)
What do you think it says about our ability to respond these types of threats in the future?

Neil Littman (Host)
Oh, I think it's very positive. I think, largely speaking, I think everyone was pretty impressed and surprised at the speed of development of these vaccines going from, basically the starting line, phase one to having, emergency use authorization for these vaccines and then being admitted, stirred administered to, millions of people at a global scale, I think is very impressive. I think the future bodes well, it's probably only a matter of time before another pandemic hits at some point, whether that's a Corona virus or influenza virus or whatever it may be. I, I think there's a lot of lessons that have been learned throughout this pandemic, both good and bad that can be applied to future pandemics and, the fight viruses in the future. I think there's a lot of really important learnings, both in terms of not only the technologies being used to develop vaccines, but really importantly, also the logistics and administration of how these, how the doses will be deployed at a global scale.

Danny Levine (Producer)
One of the things that I've noticed is that after people ask whether someone's been vaccinated, the next thing they want to know is which vaccine did you get? Do you think the general population is getting any more sophisticated about the technology itself? Or is this just a brand thing?

Neil Littman (Host)
It's a, it's a really good question, Danny. I think we have a whole lot of armchair virologists out there and, I think a lot of folks read something and then all of a sudden they're an expert in, virology and the different vaccines and the nuances, which is part of why I wanted to do this podcast to begin with is because there's a lot of misinformation out there. I think as you heard Craig say, sure, there are differences in efficacy rates, but again, it's really hard to compare the efficacy rates across different trials. The different trials have different end points. You're comparing efficacy results is not apples to apples. I think people get lost in that nuance, which can be very dangerous. So, I think the point is, any heard Craig say this, which I fully agree with is take whatever vaccine is available at the time.

Neil Littman (Host)
But yeah. I think it's a natural question for people to ask, oh, what vaccine did he get? Just, it was more, I think, curiosity than anything. It's, it's nice to see that people are asking that question and have an interest, right. And, and are curious. I think that's largely a positive thing.

Danny Levine (Producer)
There's still remarkable distrust among the population towards vaccines. As many as one in four Americans say they won't get vaccinated. Why do you think that is? Does that create a public health problem in itself?

Neil Littman (Host)
I absolutely think it creates a public health problem. I think there's a variety of reasons that there's distrust. I mean, there's a large anti-vaxxer movement, there's concerns that you don't have linked vaccines to autism, which have been proven time and time again, to be fundamentally untrue. There is no causal link between vaccines and autism. I think many people are just a little scared for whatever reason. They don't understand the science. They don't understand how vaccines work and that's part of what I was trying to do today is, education to alleviate some of those concerns. Yeah, I think it's a real problem. I think as this pandemic has clearly shown, there's a lot of public education that needs to happen in terms of people taking vaccines, how they work, why they shouldn't be scared to take a vaccine. Just having a basic understanding of the science behind the vaccines, I think will help alleviate some of these concerns.

Neil Littman (Host)
Certainly not all of them, but having one in four people saying they're not going to take a vaccine, I think it's truly problematic.

Danny Levine (Producer)
Well until next time.

Neil Littman (Host)
Excellent. Thanks Danny.