All this is Dr. Mubeen Syed from DrBean.com. Welcome to one more show. Today we're going to talk about the nasal vaccines.
So just a quick summary of this. None of these vaccines have gone in trials or some of them have gone in trial. The results are not yet available.
Some of these have had animal tests with good results and that good means that there is production of IgG that is inside the body. There is production of IgA that is on the mucous membranes and then there is production of cytotoxic T cells as well or activation of cytotoxic T cells as well. So pretty good coverage. The concern is the side effect in the nose or the local area reactions.
So imagine if you took the spray and now you are actually injecting adenovirus. in your nose. So you are kind of injecting a cold virus or virus that causes cold symptoms and so those symptoms can occur and now how badly is not known yet.
So that is a concern. Another concern is that adenoviruses are normally part of our body, part of our respiratory system. So most of the time our body knows them and has antibodies against them.
So imagine if you do the spray in your nose and all of a sudden your body actually knows them and attacks them and kills them. So before they can actually inject their DNA and they can give us the spike proteins against which we should be training our immune system, instead of that they are just destroyed even before they did their function. So these are the kind of challenges that are there.
So with this let's start our discussion and we will go from there. So once again as I have started naming these talks as gifts for humanity. So this is one more such talk. And in the same vein, I also want to thank everyone who has been very generously sending in coffees and donations. So thank you very much for that.
Okay, so let's see. This technology is very similar to oral vaccines as well. But there is one company that has technology slightly different. And I really loved that as well. It's in in line with Novavax technology.
Remember Novavax is synthetic particle. It is similar to them, but not exactly like them. So I think it would be interesting to look at their technology as well. Let me show you the links first.
So here is drbean.com. This is AstraZeneca. So Oxford has started making the nasal vaccine and now they're getting ready for the trials.
So that is one. Then there is a new company in Finland called Rokote Labs. I hope I'm pronouncing it correctly.
Rokote Lab and they have started a similar nasal vaccine and we look at the technologies of the nasal vaccine, two technologies. Then there is another company here. This is Alt Immune and they have an ad for COVID, ad for adenovirus and COVID for COVID and they have already done animal tests. and this is that link here. This is an article about the nasal vaccines, interesting article.
This is an other article in NPR about the nasal vaccines, also an interesting article. And then this is another drug company, Avalon. So if I can just very quickly make it bigger, Avalon GloboCare, which is another company that is making nasal vaccines.
So quite a few companies that are doing it. So let's now see what are they doing. So two groups of companies, I'm just wearing my gloves, two groups of companies.
One is this group. This is all adenovirus-based vaccines to be sprayed in the nose. And here there is another one, Avalon Globocare, which is a particle, an artificial particle-based company.
So we'll look into today, we'll see what are these nasal vaccines, are they better, what are the concerns, I talked about some of the concerns, what is the technology, then what is the immune response type that we are seeing with them and are there any trials. So in general trials are started, there is no result yet. Now why nasal vaccine? Just like oral vaccines. So if you see here, the nasal vaccines are stable at room temperature.
Then they can also be transported easily. So they are going to go places as well. And because they are stable at room temperature, they can easily be transported from one place to another.
Then here, this is what is important. Other vaccines, for example, Moderna or Pfizer or AstraZeneca or Sinopharm, they, because these are injected in the muscle, they primarily produce IgM and IgG antibodies. because the antigen is in the body. On the other hand, for these antigens, for the nasal and oral vaccines, we are actually bothering or irritating the immune system sitting under the mucous membranes and this immune system has a little more specialization to help produce more IgAs. vaccines that are oral or that are nasal will produce more IgA compared to the intramuscular one.
The challenge for these vaccines is to produce more IgG, which is mostly done by intramuscular. Still, I think this is an interesting thought and I believe in it. And that is that if our barriers are strong, if our surfaces are strong, and we can catch the virus right there and start beating it up and neutralizing it, then even if we have lesser IgGs, we can still be okay because we're not going to let it enter in our body that easily. So because of that, I actually still feel that these are good vaccines. We'll have to look at their side effects, but other than that.
So now let's look at the technology. Technology is the same as we saw before. Take a coronavirus. Then what you do is you produce you take some of the RNAs, some of the antigens from it, you select some things from it and decide that we want to create antigens of those things. For example, spike protein antigen, for example, matrix protein antigen, or maybe envelope antigen and so on.
So take those pieces of RNA from the coronavirus that make those specific antigens. Then what you do is And we saw this with the oral yesterday as well. I actually modified that lecture. So then what you do is you remove, you take a adenovirus. So that was a SARS-CoV-2 and you take the RNA of the interested, of the antigens that you want to produce.
Now you take an adenovirus, you make it replication deficient by removing those enzymes or genes from it. that help the virus replicate. We do not want it to replicate once it is in our body. So we remove those genes and we enter or we add the genes for the antigens that we want to make.
For example, let's say spike protein. So we take the spike protein gene from SARS-CoV-2, we plug that gene into this adenovirus DNA and now we have a recombinant DNA. Then what we do is we use this gene, this material DNA, we inject that into cell factories.
And as we talked yesterday that it was, for example, for the oral vaccine, one of the company was saying the cell factory will be yeast cells. The other company I did not know. Here we have Oxford.
If it is Oxford and they're using the same cells, then these are going to be the same issues, the clones of the fetal tissue cells. What about the others? I do not know yet.
They do not disclose their... the technology that openly. But anyways, there is a cell here. It is either from a monkey or from a fetal tissue or from a vegetable yeast or from a moth.
It is from something. This is a cell. In here, they have already added the enzymes that will help make copies of this DNA.
So when they put the DNA in the cell, that DNA will be made into multiple copies. Those copies would then go into the cell's machinery and the cells will make these adenoviruses. Now these adenoviruses have the DNA in them but their DNA is replication deficient. They cannot replicate once they are in our body. Now the problem is how do we get these DNA, these adenoviruses out of this cell?
So we will have to break this cell like an egg and remove the thing of our interest. And that thing is these adenoviruses. This is the vaccine.
So what we do is... You see here, we take these cells, we kill them, and then we have the adenoviruses coming out of these cells and then we filter them, we purify them, and we make sure that the cells debris, cells broken pieces, are not in the vaccine, just the adenoviruses are in the vaccine. So we collect them in this spray bottle We collect them and then we make spray bottles from them. If you can see these are kind of hiding in there and kind of seeing that hey I'm in here.
So these are the adenoviruses. This technology is for Oxford, for Rokote Labs from Finland and for AdCovid which is from Altimmune, I believe US-based company. So all of them have this technology. I'll talk about the other technology in a second.
So now what do you do? Once you have the spray ready then you spray that in the nose. and that would cause the adenovirus to be on the surface of the nose cells and then enter the cells and once it has entered the cell, we have done this discussion many many times, what will happen is this phagocytosed adenovirus will be dismembered, its limbs will be removed, that is the spikes, the remaining broken and kind of damaged adenovirus is hauled to our nucleus That nucleus would then allow the nucleopore, there are holes in the nucleus wall, and it attaches to that hole. Imagine a window in the nucleus, and then it would inject the DNA in there. That DNA would then be converted into or be transcribed into a messenger RNA.
That messenger RNA would come out and our ribosomes will make those antigens that we want to make, for example, spike proteins or other proteins of this virus. These will then be shredded in the endosomes, loaded on MHC1 or MHC2, presented on the surface, and then the immune system would respond. I don't think that they have this TLR3 agonist. They would have something else compared to them.
So this is the immune system's behavior and now what is the expected outcome? So we do not have any phase one trial or phase two trial results. So we can't exactly say what will happen.
But there is one interesting thing and that is, if you see here, this one. So this is Altimmune and their vaccine is adenovirus, ad-covid. And if you see here, this is the animal trials. And it is worth reading.
And I have all of these links in the description. So if you see here, Altimmune recently announced the results of highly successful animal studies that demonstrated strong activation of the three critical arms of the immune system. Although there are not three critical arms, there are two arms, but anyways they've taken some liberty with the words there, with the immune system following a single intranasal dose of ad-covid, namely serum neutralizing activity. So they are calling these three the arms.
Neutralizing activity, that means production of IgG. Sorry, this is the IgG. IgG against spike protein will be neutralizing activity and that is adaptive arm.
Then T cell immunity, and T cell immunity will mean cytotoxic T cell plus memory helper cells. That also is part of the adaptive arm. And then mucosal immunity which is IgA, which is also part of adaptive immunity. So essentially they are saying that we would trigger the adaptive immune arm, which will produce antibodies and trigger cytotoxic T cells. This is a normal behavior.
If I was writing it down, I would have said, hey guys, we produce a lot of IgA compared to others. We will protect the barriers. That is a more interesting thing than to kind of incorrectly call them all three arms.
But anyways that's just wording. Now check this out. In the animal studies, here is what they found, and I love this one. Check this out.
Serum neutralizing activity. That means IgG against the spike protein. A serum neutralization titer of 1 to 580 by day 28. So remember yesterday when we were talking about oral vaccines. We said that some folks were disappointed that the neutralizing titers were not produced. Here in the animal studies, they are already seeing that by day 28 IgGs were produced.
So this is several fold higher than the immune titers recommended by FDA. So I'm going to leave that here. Then T cell immunity. So that would be this side, this weird T cell. It makes me laugh.
I should have given him better expression. He's a friend cell, but he looks in stress. Okay, so a potent stimulation of antigen-specific CD8 plus killer T cells in the lungs of mice as early as 10 days after vaccination.
You take the spray today and within 10 days, the T cells, cytotoxic T cells, CD8 plus cells or CTL cells will be active. Awesome. Love it. And then mucosal immunity, mucosal immunity will mean IgA, a 29 fold increase in mucosal IgA, well above the level associated with protection in clinical studies of other vaccines. Mucosal immunity can stop both infection and spread of the virus.
It can protect from incoming infection and outgoing infection as well. Beautiful mechanism. And then they say, hey, we are superior. product stability.
We don't need those freezing and frigid temperatures. Okay, let's go back here. So they produce IgA, awesome.
They produce IgG as well, which was not evident with the oral vaccines and they activate the cytotoxic T cells too. All good, amazing. So I love this one. Continuing on, now let's look at the second technology. Did you like this SARS-CoV-2?
It is kind of looking at you like this. Look at his eyes expression. Okay, so second technology that is this one.
Which one was that? I think this is the one COVID vaccine. I think this one, Avalon GloboCare. I love this technology. So they have a bunch of platforms already.
Down here, if you reach this far, this is the S-layer protein. So without explaining that too much, if you would then see here, it would say SARS-CoV-2 vaccine using this one. Mucosal intranasal COVID-19 vaccine, Avalon is also using its S-layer technology in an intranasal spray vaccine.
So let me just very quickly explain what do they mean by that. So here is an actual SARS-CoV-2. And we do not want to spray it in our nose because it would cause infection and may even kill us. So what they do is they take parts of this virus, just like, remember Novavax? They take spike proteins, make them separately.
Then they convert them, Novavax, they convert them or plug them onto an artificial... little particle and this to our immune system looks like the virus because it has a size of the virus it is a Form of a particle on the on it are spike proteins attached to it Our immune system goes nuts looking at that thinking it's a virus, but it is actually not a virus That's what they do over here as well So what they do is they pluck some proteins from this virus or they make those proteins Then they have a technology where they have particles that assemble in the size of a virus and on the surface of the particles these antigens, these proteins will become installed. This is all happening at micrometer or smaller size.
So these particles are formed, that is a technology, that is what they call S-layer technology and then on the surface of the particle pieces of SARS-CoV-2 antigens are installed. So this is like a rag doll with the eyes on it and ears on it or you may have seen for Halloween in the US. Remember sometimes people have those little arms, human arm like things coming out of their car's trunk and it looks like there is a dead person in there. So that arm is a very similar thing here that this is imagine this blue thing is the car.
and then on the surface of it are attached spike proteins. So it is kind of a Frankenstein particle with the antigen. So when they inject this or when we spray this in our nose, it is not an adenovirus to cause infections. It is not even a SARS-CoV-2 to cause infections, but it has some antigens of SARS-CoV-2 and our body would just attack it.
Our immune system would attack it. The results are the same as above, but technology is different. It's a very different technology.
I love it. So then... Why this technology? Why nasal sprays? So the reason for that is that number one, the adenovirus, no chance that adenovirus antibodies may be present.
So it is possible. So this technology, the particle technology, the one that I just showed you, because it doesn't have the adenovirus, if somebody has adenovirus antibodies already in them, then a nasal spray with adenovirus might get destroyed before it functions. But if we have this Frankenstein technology, they call it S-layer technology, I'm calling it Frankenstein technology.
So if we have the S-layer technology, then adenovirus antibody issue goes away. That's one. Then of course, then our body does not react to adenovirus even if we don't have the antibodies, but we are going to experience it for the first time. we are not going to attack that like a virus. Better vaccine design.
So now they can design the vaccine and they can decide what antigens to put on top of it and so on. And then possibly less side effects. We still have to see that.
So that is the discussion for today. What did you think about this? So we'll do a few more minutes of talk then we would meet separately as well.
Do you like this technology? So there is a separate discussion going on. All right. So I'm going to see you in chat in a second. So do me a favor, please like, subscribe and share.
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