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>> Good morning, everyone, and welcome to national fans forum and the spring 2120 already one cities we are focusing on. We are focusing on nanotechnology and vaccine that way. And we have today even the anderson from emory newest, the school of medicine speak to was on this topic, m R in the back scenes.

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And go with 19 to start off a new era of ex, lax and ology ill be speaking on that. And so before I introduce professor anderson properly, i'd like to share with you a video of cynic program that is a flagship program at the institute for electronics and man or technology.

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You know the non offense forum sponsored by south easton manor technology infrastructure corridor, which is one of the 16 n N C ice sites under a special program called under national science foundation. And so please enjoy this video related to scenic vision and mission. The South eastern nanotechnology infrastructure corridor, or scenic, is a partnership between the Georgia Tech institute for electronics and nanotechnology and the joint school of nano science.

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And I know engineering and academic collaboration between north Carolina and state University and the University of North Carolina at greensboro. scenic is a part of the enter, self funded national nanotechnology coordinated infrastructure. A network of 16 academic centers and their partners provide open access to state of the art not on fabrication and characterization, facilities, and stuff, expertise across the US.

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This network also supports education and outreach programs, as well as societal unethical implications and none of technology activities. scenic as this researchers from academia, industry and government labs with their micro and none of fabrication and characterization projects seen as users work in areas such as electronics, mens sensors, biomaterials, photonics and materials growth and synthesis.

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Our facilities can also meet the unique needs of non traditional researchers from discipline such as life sciences, biomedical engineering, and health Care. scenic also offer a short courses, hands on learning experiences and micro fabrication soft photography and characterization techniques. More than 1300 researchers use our facilities annually. training is available for users who are not members of the joined school of science and not only jerry or georgia Tech communities to access the tools they need.

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scenic also enables remote work allowing researchers to send samples for processing or analysis buyer experience stuff. scenic offers broad capabilities in e B, lithography, photo lithography, then film deposition edge processing, metal ization, package, micro cl printing imaging, spectroscopy, metrology, micro analysis, analytical chemistry, material testing, laser micro machining, and computation for more information on scenic facilities check out our website at scenic dot ga, tech dot edu.

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For more information, please visit our website clinic dot ga tech dot d D U. And let me also give a little promotion on the upcoming events. Next week may 19th, we have pro m g fin will speak on wireless like particle approaches to corner wires, diagnostics and maxine's.

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He spoke about this topic last year, but it's more of an update to him. And then on May 26th, we'll have Dr. colina bronowski, a sca speak on lippard, nanoparticles for in my will, m R, and the delivery. So if you have not signed up or if you know of a colleague or a student who may be interested, feel free to at, you know, ask them to sign up the link.

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tiny you are are you are url dot com slash nano fans. spring 2021. With that said, it's a pleasure to introduce prov sanderson this morning to speak on this topic. And marnie vaccines, and cole were 19 the start of a new era of facts and ology. evan anderson is a professor of pediatrics and medicine at emory university school of medicine.

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He graduated so mac m latiere from read and college it and I after which he pursued as medical degree at the University of Chicago for his car, school of medicine. He remained at a university of Chicago for residency in both internal medicine and pediatric following, followed by an adult and pediatric infectious diseases, fellowship and B, not list and memorial and Children's memorial Hospital in Chicago.

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He moved to from not listed to emory university in 2012 where he is attending physician at children's healthcare of Atlanta in pediatric infectious diseases and m marine those 2 hospital in order to infectious diseases yourselves as the lead investigator in Georgia for influenza r 3, which is the respiratory since she'll send you all the wires and go and 19 surveillance for the cdc 100 emerging infectious infections program.

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He is currently one of the multiple, the eyes of the emory university vaccine and treatment evaluation unit and has been intricately involved with the code, 900 vaccine clinical trials for montana and also johnson, which is johnson and Johnson. Over in 1900 maxing, he particularly enjoys mentoring trainees at all levels and received the emory department of video to research mentor award in 2017 years or $150.00 total publications with particular interest and wrote a wireless ours we influence and coord 19 early phase vaccine clinical trials and the power of Community protection.

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Now it's my pleasure to invite pros, anderson on behalf of national fans audience to speak on this topic, m R, and a vaccines and co. 19 the start off of you era of vaccine. ology for sanderson Will be talking them are in a vaccines and covered 19 the start of a newer and vaccine knowledge, and I left it with a question mark for a real purpose here.

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So I do have a bunch of financial disclosures, notably i serve as the p I for the modern and jansen studies. Those listed below, i don't have any direct compensation from from those groups. So 1st of all, outlined impressive accomplishments. So the response to code 19 and then 2nd, discuss the potential application of them are in a to the future of acts knology.

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And is this really the start of a new era of acts knology. So we'll start with the 1st question, but when we think about a paradigm shift, as far as an approach to a new vaccine approach that could, could really change out. Things are done, but it's needs to be new technology.

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Second is that one would want it to be flexible, where it could easily switch between pathogens or adjust to potential variance that arise over the course of time. 3rd, you'd really like a speedy technology where you can move quickly from concept to vaccine in fairly short order. Next precision.

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So we do want a focus, but robust immune response and try to avoid an overly broad response that the perhaps provides binding in our bodies. But not actually neutralizing in about one immune response that will be durable. You want to back seen that safe. We need the vaccine to be scalable.

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Without that it's difficult to advance vaccine to general use. You want a method that can be use kind of again and again, meaning Where it can be used for different vaccines or for boosting of vaccine doses over the course of time without safety issues. ideally, we want a low cost vaccine.

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And then also we want to be stable, where can avoid a lot of the cold chain issues, the extent to which any vaccine meets most or all of these criteria. Then could asher usher and the possibility of a new era in max knology. And the reason I took a little time to go through this is the very beginning.

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And so you'll see as I talk through the M R and a vaccines and cover 19 you'll see some of these areas where this is really unique technologies. So 1st they did, why just take a 2nd and really highlight the fact that will give just a great talk last week really enjoyed it actually learned a tremendous amount of things and definitely worth while going back and and doing that, if you can.

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And I look forward to the future lectures as well. So this is 1996. And you'll see here this was the vaccine schedule for children in 96 total of 123456 vaccines, of which really multiple of these were live attenuated vaccines. So the bottom 3, you've got a protein vaccine talk, so it vaccines and hepatitis b vaccine.

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So if you can, for them 2021, you can see the things of dramatically changed where we have many more vaccines that are routinely available. Those are all highlighted in red, where there's been a significant change in how we administer the vaccine. I've also highlighted with the right arrows where it moved from all the oral polio virus and seen 10 activated polio virus vaccine.

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We've moved away from whole cell to our process, vaccines as well. The prayer approaches to vaccines kind of work in the 6 general categories here. So you've got it recombinant purified, an engine with hepatitis feed. We have the classic live attenuated vaccines that add to meet those monster bella parasol and wrote a virus.

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Those that are less commonly used in the US include the oral polio vaccine, b, C, g, typhoid, yellow fever and m B A you have killed are in activated whole organisms. And these have been one of the mainstays of vaccine ology over the course of time. But increasingly are probably moving away from these in the process of killing or in activating the whole organism.

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You may have a non specific protein mutations that happen, that might result in a more broad but less, less effective immune response. In conjugate your protein to carrier protein such as a head and the 13 **** vaccine. You've got the purified protein and post sac right vaccines and then talk so back scenes of course.

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Now, in this new era, we have several vaccines that have moved all the way through to life insurance. So 1st is there's a bowl of actually in this license in the U. S. Using champ and vector. And then the add 26 by protein for covered 19 made by chance.

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And then the new m R and a technology though, how do we get here? So this is slide i like to show this is I'm how we got here. It's our relationship with our animals, and yes, that is about that. That girl is kissing. We should have been a little bit are prepared for covered 19 and we were.

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But there was some key critical preparation that was done in part because of the original emergence of 1st stars cross virus, and then the merge corona burs. subsequently, in 2013 worse by January of 2020. The red dots had, had quickly spread from their initial cases in China worldwide.

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One of the ways in which we were prepared and this is something worthwhile, highlighting is the, is the real benefit. translational and basic science work. And so when one thinks about code 19 here on the bottom on the left, you can see that there are a number of proteins including spike nucular, protein matrix protein in the low protein, all of which I could store serve as potential targets for vaccine in work that had been started prior to the covered 1900 pandemic, and finish and publish post barney grams group.

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And I h looked at using a M R and a vaccine for merced karone of ours. And in that they administered some mice, essentially sailing and then varying doses of immersed s T p protein are in a vaccine. And you can see with increasing doses you get increasing neutralizing in bi titers as well.

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The mice were then challenged with, with mergers. And in essence, you can see that mice that received placebo had a large amount of weight loss. They had a large amount of virus in their lungs and they had pulmonary hemorrhage. Those that have received actual vaccine were protected. And so those form some of the basis for allowing for size to begin in humans.

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Before we had for safety data from animals, we now have the full safety data and animal well before starting the phase 3 studies. So when one thinks about of ag seen you, of course need to manage and sd, but you need speed of development and safety to coexist.

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In part because once you administer vaccine, you can't take it back. So we start with slow enrollments for sentinel subjects, pauses and enrollments and to slow dose escalation. safety and react intensity frequently are confused in people's minds. So reactors, necessity is our side effects that we expect to see are related to the vaccine so that that would be a local symptoms, pain, redness or intent, and sort of the side of injection or the systemic symptoms of fevers chose achiness, body muscle aches, headache, noise, in the day or days after receiving a vaccine.

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In general, we've been focusing on trying to minimize reaction density for many of the vaccines. However, I think a good lesson does exist from the shingle bank seen where this is clearly safe. And with that, we see a much better immunologic response to sugar faxing than we saw it to the live attenuated shingles vaccine.

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One of the key publications, in terms of understanding safety, was this paper by barney graham that summarize some of the safety concerns that might exist for a vaccine. Of course, we've seen rare occasional severe side effects from vaccine including swine flu being associated with again brace and from in the mid seventies has been antibody dependent enhancement of disease with banging.

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And then one of the real classic examples where things do not go well was lot was a in activated re fi vaccine that was in activated with formal. And with that, they saw the vaccine associated enhanced respiratory disease, in instance, that we're subsequent infected with our a C.

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One of the concern about that was due to the fact that the seem to be both painted by immediate and also t cell mediated response that occurred. There was some early concern about the possibly that this could also be the case for the corona versus in part because the feline infectious parent night as fire among others may be associated with increased disease.

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And so this was a potential concern, and so there is a real focus on trying to achieve a th one biased response. And then also a confirmation, correct. An engine that generates a high, neutralizing inner bio tighter and look for that day. And as I kind of talk to the rest of the presentation, so for the platforms that, that might be used, of course, live attenuate and activated vaccines have not move forward here in the U.

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S. Live attenuate in part because it's hard to rapidly live attenuated vaccine and tone down it's, it's potential for causing illness while preserving it's immune response. But then activated vaccines because of the concern about potentially developing binding but non neutralizing in our bodies. This did not move forward in the U.

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S, but it's moving forward internationally. And then there's the 3 primary strategies that have been used, the operation more speed. But then in many ways, i think helpful in terms of understanding how we got to where we're at. So there were 3 in the ways this was a brilliant effort on the part of u.

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S. government. I think in hindsight, and even at the time it was still, I mean, it was also brilliant at that point in time. But I think in hindsight it's, it's quite clear that this was a very effective strategy. You know, and see us government purchase millions of doses of vaccine from all 6 manufacturers.

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Or all 6 of these manufacturers using 3 different platforms to different manufacturers of them, are an, A 2 man different manufacturers with the borrow vector and 2 s protein based vaccines. Now we've seen 3 out of those 6 make it all the way to the finish line, an F d A approval.

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There. The other 3 asters danica has had a lot of issues related to their, to their safety, which I can go into if people have questions. And then the S protein based vaccines have been a bit delayed. So none of acts did not started their study until much later.

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So you see speed is clearly not as much of an issue or it was more of an issue for them. And then sanofi actually had some significant issues with having insufficient manage and in their initial phase to study the for those of you nano fans that are out there.

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This is, this is definitely a good publication for you to look at. This is from the onion, which of course, publishes everything kind of tongue in cheek and title. The nation cannot believe they've spent so long. overlooking the obvious solution of m R N, A instruction for spike protein and capsulated in leopard nanoparticle.

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So again, for the narrow fans out there, you of course, knew that this was going to be the best approach. But for the rest of us, we are a little slower in the uptake. This is one schematic, cartesian demonstrating how it's thought that the vaccine might work. I think that there's a tremendous amount of work to be done, really understanding what actually occurs here.

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And the extent to which, to which uptake is happening and muscle cell vs and in lymph node. But in essence, the overall concept is the following. You package the M R N A within a delivery mechanism in that being a liquid nanoparticle that lip nanoparticle does what methods do best, which is fuse with cells, leasing the same r N A into the cell.

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The cell then translates the M R N A to create viral proteins that either remain on the cell surface or get share that extra cellular. Some of it also gets granted through proteus, owns and presented through m h, the class, one to city itself. Also, there is some extent to which there's uptake by the ash presenting cells of both potentially fashion as far as energy made by other cells.

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And then also translation of that m R N A. To create viral proteins that are then degraded through pretty Little those calls and presented through m h, the class to mechanism. So that's the general thought of how the proteins made how they get into this whole process of being involved with the vaccine clinical trials.

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This in part due to my involvement with them re vaccine treatment evaluation yet, or I'm on a multiple p i's on that. And in essence, we've had the opportunity to work against many of the emerging pathogens worldwide. Though we were involved the phase one study of the maturity of a scene and in essence you can see several things.

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So I have the red arrows on the 100 microgram group so that you keep track of that dose that actually move forward. And you can see that at the 250 dose, there was increasing reactors. And that's to be from us, from a systemic standpoint, and particularly fatigue, fever, shells, and headache being fairly frequent for the $250.00 microgram dose.

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In essence, after we had given the initial subjects that vaccine decision was made to move forward with the 100. 0, so we in essence found a dose limiting reactor janessa be ended up being an issue at the 100 doubts From that standpoint. We then essentially saw as well that at that $250.00 doses, the real flattening in terms of the binding responses which are here on the top, both as to pre p and also to the receptor binding domain.

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And then the seat of neutralizing antibodies which are easier to identify quickly and to test quickly. You can see that there's a boost that's happening immediately after one week after the 2nd dose of axis, which is given on that day 29. You can see that as well, there's a 10 for the increase in binding in our bodies that also happens at that time point on the challenges as having a compared or, or these initial studies.

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And that there was not, not a overall standard for assessing those immune responses. We saw them in the older adults. And there that we pop up, published later. In essence, a th one biased response, which is really what we were hoping to see your data then in the older adults.

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And I'll just take a 2nd to kind of highlight the fact that in those 50 to 70 and about 70, we see him in responses in terms of classic, neutralizing enterprise, which are peer and t's that are in the similar order to those observed in the younger adults from the modified neutralizing and say which is F R N T which who are from our group really has has, has been very successful in terms of moving forward.

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What you can see is that So here's the peer and T, which is the classic method of evaluating neutralizing bodies. The best correlating assaye is his f R N T say. And the correlates actually much better than total total binding antibodies and also some other pseudo neutralizing and neutralizing acids.

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So your branding, i've seen this as a moving forward a lot in terms of assessing neutralizing antibody responses by the phase 3 data. Then this actually demonstrated what we had seen in the phase one studies, the most common symptoms being pain at a 15000 mile, shortly after receiving vaccine.

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That also holds true for the pfizer vaccine in general, for both of the vaccines. Second dose is a little less while tolerated than the 1st dose. That's perhaps a little bit more apparent with the data from the during the study. But it's also true for the highest maxine and then pain really being the most common symptom.

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And in the majority of individuals, if you look at the data as far as efficacy, so this is, remember any subject to develop symptoms potentially consistent with code that we would bring them in, draw blood and then also do n p swap. And in essence, you can see that beginning at Day 14, there's this real diversions that happens between the number of cases occurring and those that receive vaccine on the bottom.

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And those that receive placebo. On the top though, beginning of divergence in terms of efficacy, even at that point in time. Of course, then we've got the 3 vaccines that are moved all the way forward to you. A and number of them are apply in the midst of applying for v L A.

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So for full licensure, the residual questions exist post the phase 3 studies. To what extent are those reaction is the side effects due to the liquid nanoparticle versus the actual i'm are in a that's creating the spike protein. We don't know that answer. That's a really important question for which really good answers are needed.

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The longer term safety is not well known, but we do have data now out through so over 6 months for pfizer. mcdermott for the phase 3, for the phase one now up to 12 months and about and again, the fax is one of our application and transmission and vaccine failures or some preliminary data suggesting that they may be successful in terms of doing that.

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We need additional advocacy data about the hospitals ation impact and death impact. Although preliminary data look good and then correlates the protection really need to be determined for corporate 19 immunocompromised patients. pediatric patients, pregnant women, all need additional data, improve standardization of the houses, and then can we safely boost prior participants, what doses needed, and what's the safety for various vaccine and data that was published from israel post licensure in essence, they have been able to demonstrate with the pfizer vaccine, where it was used exclusively, again this efficacy really beginning about a 14 in actual african c against preventing death.

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But the very question, which is a really important and critical question. I'll take just a few minutes and talk that through. Here on the top, you have infected patients acutely with covered convalescent patients in vaccinated individuals. similarly, on the bottom, we have acute infected convalescent and, and vaccinated individuals with the maternal vaccine.

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This is again, data from a cool, but in essence shows a preserved activity against the U. K. variance, which is the B 117 variant, both in acutely infected and also convalescent individuals. And you can see that that's also the case and those that have received vaccine. importantly, holes out is consistent across all 3.

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And in essence, you see higher enter biters even then you see post natural infection. Same thing and those kind of info graphic are there's, there's not as great a slide specifically within that paper. But in essence, you can see that this infographic kind of demonstrates a similar phenomenon where you see overall the activity against the South african bridge variance, which is the B 1351 is lower than those that have against the original strain.

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But it still is active and it still is active with higher neutralize insiders than you actually see with, with National infection. So what happened is that madonna, and now we know 5 or as well, have launch actual studies of the varian vaccine. And we're conducting one of those at emory, actually sort of those studies and emory evaluate very and vaccine focusing primarily on the South african variant.

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The preliminary data from actually now multiple studies is suggesting that there is still preserve some degree of activity against against the South african variance. So this is data from the jansen vaccine, which was conducted primarily or extensively in South africa. And you can see that in comparison to placebo, there's dramatic decrease in terms of cases and those that received vaccine.

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novak's recently published their data demonstrating a similar phenomenon. And then as well for the fines or vaccine. You can see that for the 1351 which is the South african variance is preserved activities. So 75 percent efficacy versus about 90 percent african c for the B 117, which is the U.

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K variant. And then looking against severe disease both or $100.00 or was effective 100 percent against both importantly, the chip bad ox vaccine, which is the answer is anchor maxine, they actually did not demonstrate any actual efficacy of the vaccine against the South african berry. And there are some reasons for that, not potentially due to the fact that they didn't use this stabilized by protein, which I'm happy to talk more about.

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People are questions from a safety standpoint. We know, in general that, that the M R N A vaccines are saves, and we'll go into exactly how much, how many those have been given so far already. The very system which is used to identify these rare side effects but cannot determine causality.

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Essentially identified a risk of handful access with modernity. pfizer being roughly about 2 and a half to 5 per 1000000 doses of ag seen, administered that's actually not far from the baseline risk of being struck by lightning. And in any individual year, which is about $1.00 per 1000000 people.

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So it's very, very rare of it can happen and this is probably the most important side effects that's been noted to date from a safety standpoint. Though, to summarize this section, we were minimally prepared 1st harsco b 2. But the investment that we did make in basic fans is really critical in terms of moving forward vaccines.

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Quickly, there multiple novel approaches to targeting spike were successfully utilized to result in safe and effective vaccines, both with m R N A and also r O vector vaccines. The M R N A is perhaps a little more reactive genic than the bio vector vaccines and potentially also the other protein based vaccines.

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We really don't know enough data about this, but there is some suggestion in the available data that probably has more symptoms associated with it. Do you see a decline in antibodies occurring over time? And question is the people need a boost and was the safety of that. And then concerned about variance with the South african bridge being the most concerning.

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So when we think about the big question that we start the question mark that I start the lecture out with, hopefully i've been able to convince you that in essence, most of these, for which I've shown you with the stars, those issues seem to be mostly resolved where there's some questions, is the durability of the response, is the same scalable.

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The general method that is this a general method that can be used again and again. What about the cost? What about the stability? durability, here's data that who and raphi a med and I and may others were involved with generating in essence, in those that were convalescing from prior source koby to infection anemia.

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Since you can see here, this is a measure, and I'll just have you focus on the highlighted box here in this pre print of our b d. And in essence, we looked at the kinetics of the decay in terms of our b, d, titers by using 2 different methods with arguably the power law perhaps being the most appropriate because it takes into account kind of that there's a curve that's occurring here.

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And in essence, you see that that's about 116 or 209 days for the how flights of binding in our bodies post national infection. Looking at the data from them, our initial medina participants. We see that that half life is perhaps a little lower. In comparison to natural infection but but importantly to harvey deed units here are very different than the redo units that are used in the study.

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verbal who really comes in is then looking at the neutralizing antibodies. In an essence that power law calculation calculates out the neutralizing in our body half life of 254 days. When we looked at our participants in the phase one study, you can see that, that we're talking about 202 days for, for that.

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So that's probably not a statistically significant difference. Also the other key thing is that in on jet, in general, or I'm sorry, the scale here on the units is actually the same. So you have your vaccine recipient starting out much more over the 1000 in terms of neutralizing bodies.

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And then they do decay, but they get down closer to 100 rather than or above $100.00 rather than less than $100.00 with natural infection. So, so kinetic savannah by to k is, is, at least as is favorable in terms of comparison to data source could be 2 national infection.

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Next key question is, there is a M, R and a technology scalable. So it may not have been scalable before, but I think there is no doubt now that it is so this is the total number of doses administered and then the total number of doses delivered are manufactured here in the U.

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S. For distribution. So with 5 further up to nearly a 175000000 for maternity, 140000000 doses of ac seen this is data from cdc And them can these vaccines be used again? And again, this is really, I think probably the most key question and hopefully one that many of you will be able to help answer in potentially help sort out is, is the question of lippitt nanoparticles.

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So it does appear that some of the allergic risk may be due to the liquid nanoparticle and potentially the peg peg. That's in that. So is it going to be safe with administration of multiple doses with a late boost occurring over time, or with as part of a different vaccine.

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So you're covered vaccine now. And what happens if we use it for the prevention in the future? Is it going to be safe in that setting, since you had received this faxing previously using this fame? potentially similar, looked at nanoparticle importantly, minturn had just recently. And as you know, things are usually published now by press release instead of actually with hard data, which is a whole separate topic.

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But in essence they know that a single booster dose of m R N A or the variant increase neutralizing antibodies. Again, far as could be 2 and 2 variants of concern and previously vaccinate clinical trial participants. So that's really reassuring that you can boost immune responses when they also know it.

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In this press release. That time it did appear to be safe from the manufacturing capacity. So they know it as well that they've increase their supply forecast 420212800 1000000 to 1000000000 doses with anticipated up to 3000000000 doses developed by 2022. So scalable. Yes, definitely. key criteria for mer, major paradigm shift continued.

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So the cost, so this is I think one of the potential limitations and the limitations as far as its ability to expand worldwide. This is expensive technology and it's not going to be available outside of resource resource rich settings in the short term. However, there actually are some manufacturers of m, R and a vaccines that are popping up internationally that are moving into clinical trials.

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Now the key question is how stable is the vaccine and the ability to avoid cold chain issues. You've probably heard a lot about the issues of pfizer vaccine in the media. And clearly that's a significant issue and, and problem but does appear the progress is being made and, and likely will continue to be made on the part of the vaccine manufacturers.

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Because this is Roy a key issue for being able to expand their reach worldwide. I'm. So I then pulled up essentially a cross match between them are in a, in vaccine and clinical trials. Of importantly, the vast majority of the studies listed are covered 19 and covered in 1900 various studies.

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However, we see vaccines when corporate trials for c M, B H M, P b, and para influenza type 3, h, b, influenza, rabies, r, S, B, and C. This is really remarkable. You've got pretty much from c to Z as far as viral pathogens go. Already entering into the vaccine clinical trials.

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Now, I think that that, you know, obviously the carbon 1900 size are going to continue. What's really interesting is that there are several kind of holy grail vaccines or potential pathogens here, for which we don't have great vaccines, including our s B, which perhaps is the easiest of the, of the viruses to potentially target.

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Since overall it doesn't have a net mutation occurring. However, each i be in influenza certainly would fall into the category of those for which we would really like that or a vaccine or a better vaccine. And so be very curious to see how these studies move forward for influenza in particular.

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I mean, one can easily see if you've got the ability and capacity to make potentially 1000000000 a 1000000000 doses in a year. That means that you should be able to, you know, wait until well after you've identified influenza strains that are sort, appealing in the southern hemisphere for fear and then ramp up production quickly of a new flu vaccine that contains the most the most recent influenza circulating viruses and a much shorter timeframe than we've ever been able to do for base technology.

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So I do think there's tremendous potential. Of course, all of these are going to have to undergo careful evaluation. And as well, the safety of repeated doses of lead, banana, particle i think is the key question. And then you also see it moving forward, actually pretty quickly into the cancer treatment arena.

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So with that, just note my acknowledgements and search for vaccine does continue on and obviously we're thrilled with all the progress we've made in terms of having a adult vaccine available for covered 900. That's very highly effective and safe. Happy to take any questions. Thank you. Dr. Anderson for your very informative presentation.

[00:40:47]
I'm sure we have a lot of questions I guess. So let's go with played those question and I be glad to read it. The 1st one is from eric woods to questions. Can antibody data be used to measure response to vaccine if it was given to an immunocompromised or elderly person?

[00:41:07]
That's question one. And number 2, practically for immunocompromised or elderly patients. Since the modem back seen uses 100 microgram m R N A and it's more the actual genic. That's the data support using it for that population. Yeah, so Good question. So in general, in those that are older, we actually do tend to see a little less reactor in this city than we do in the younger individuals.

[00:41:37]
And so this has been seen really for both the pfizer and also the majority of vaccine where, where as you get older, you tend to not have as much of the reactors in the city symptoms. So that is a kind of important thing and it's not been very extensively studied.

[00:41:53]
Each of these have been extensively started in these huge trials. And then really, you know, with roughly 140000000 doses pfizer vaccine administered in the US already. And I think it's over a 100000000 in the maternal vaccine. It's really pretty remarkable. As far as the amount of data that's being generated on the we don't understand the correlates of protection very well at all.

[00:42:17]
We don't have one established that is a major focus. So a lot of the ongoing research is tied under fi. A correlate of protection or correlates of protection. That could help us in terms of prevent predicting who may not have had a good immune response or at what point in time might a boost dose maxine be needed.

[00:42:37]
And so those will be hopefully those data will come out over the next month. And definitely that will make a big splash because that will then give us a better idea of when a boost might be needed. And are there groups of individuals such as the mentor compromised or the very elderly or very frail, for whom additional dose or, or additional boost is needed?

[00:43:03]
Thank you. The next one is from when you car in terms are correlates of protection. Do you think non utilizing functions of antibodies might play a role at all? Have these functions been looked at? So that's a great question. So. So we've been very focused on neutralizing antibodies in part for good reason because those do seem to correlate kind of across multiple different vaccines and multiple different pathogens within the fact of immune response.

[00:43:37]
But that's a broad generalization. First of all, 2nd of all, we don't know whether it holds true for 1st ours can be 2. So there are very active efforts to look at non neutralizing antibodies and non neutralizing by function. So we actually it with my group and developed a functional, a T, C, C.

[00:44:00]
I say that we've published data on and I hope to have some more information about the kinetics of over the course of time. To what extent is a D. C. C. relevant and some of the other functional antibodies that are non neutralizing is a, is a really important question.

[00:44:18]
And we clearly need a lot more data to help to begin to sort out sort out the answers to that question. You know, mother, one has, doesn't seem that all advert to lack scenes about risk having to have a risk of lead glance since we see it bought johnson johnson.

[00:44:41]
M A Z. And would you expect this problem to merge with the sport make relaxing? Yeah. So so yeah, we did see, oops, trying to or up for you here. We did see that issue arise with the aster banker vaccine from a safety standpoint, with several important publications noted.

[00:45:08]
And then with the jansen vaccine, this is also identified. notably, this risk here is really quite low. So I mentioned this in the midst of the presentation. In essence, if you, if you look at the risk, it is really close to the risk of being struck by lightning in the individual year.

[00:45:28]
Which is about a $1004.00 less than the risk of dying of cove at $900.00, some sort of the pan down. So it is a very, very, very, very, very small risk, but it is a risk. I think that since we've seen it with the bad vaccine and also the ad 26 vaccine, that's the chance in vaccine.

[00:45:46]
I think it may well end up being a had no virus specific risk that exists in that could be an issue for that technology in the future. I'd say right now we need more information and data to be able to sort that out. Yeah. Other questions from doug when there's a question that I had in mind as well, is the current we're in in India unique or the back scenes effective against it in the currently, as you know, it's be 1617, it's very acto in India, creating havoc all over the country.

[00:46:24]
So. So, so all these actions effective against it. Yeah, it's a great question. So unfortunately, right now, to my knowledge, there's not good data looking at looking at that issue. It is a major concern and there are people very, very actively working on that, including the whole and many others that hopefully will be able to give us some insight into that in the near future.

[00:46:52]
Right now, I think it's a big question mark. One of the questions I had in mind is, you know, as we can see various radians showing up when we started with the 1351, and now be 1617. As these radians emerge. How well the scientific community is prepared to back these and appropriate b vaccines to support or, you know, to support people will been infected.

[00:47:22]
Yeah, tom, is it again, her great, great question. From that standpoint, the initial variant that kind of emerged and everybody got real worried about was, was a single point mutation, d 614 g that emerged shortly after after immersion. So the, sorry, covey to and then the current versus r N.

[00:47:50]
A viruses, unlike all are in a viruses, they are not particularly good at replicating their, their genetic material in a fashion that's that has a high, high quality of replication, but instead are very, are prone in that been results in this ongoing potential for, for potential development the variance that could find any logic weakness of axiom or prior infected individuals.

[00:48:23]
And so we're going to continue to be an issue. I think one of the key things here Is You know, what we're generating the data is really, really important. And I think that for example, in the whole data here looking at the U. K. variance is really very reassuring that both that you keep variance and then also other variance, some of which are included in this publication really are not an issue too much of an issue in terms of escape.

[00:49:00]
The big one that we worry. Everyone is much more worried about is the South african variance in part because it's not, it's the cumulation of multiple mutations that have happened not just in the receptor binding domain, but also outside of that and the rest of a spike protein.

[00:49:19]
And you do see some impact upon the ability of sera to bind in the laboratory and say, in general, the data in people has not been relatively reassuring that we're not seeing a huge amount of breakthrough due to the virus in vaccinate individuals. shortly after receiving vaccine. However, the concern is over the course of time, those enter biters may wayne, and you may start to see more breakthrough infections occurring due to some of the variance.

[00:49:50]
So a lot of really good questions like many, much uncertainty and say in general the, the responses that we're seeing to the, to them are in a vaccine are broadly cross protective. With the exception that if you, if the virus has been able to develop a bunch of mutations, then it may begin to start to scape.

[00:50:18]
Thank you dr. Anderson. And another question from got some arse loaners inactivated. vidas lack seen have generally proven less effective than in marnie vaccines, but it is in use in many low income countries. Do you think people receive inactivated wireless vaccines will eventually need to receive emr near vaccines to your knowledge.

[00:50:40]
Is that a study for receiving a morning vaccines after in activated wires, vaccines? Yeah, that's a great question. So as I kinda talked about the very beginning, inactivated bank themes, it's a very simple technology to century, killed the virus and then administer it. And that's been a major approach for a number of the manufacturers worldwide.

[00:51:08]
Has such the concern is always with doing that that you may end up developing meet changes in the protein that may result in the vaccine being less effective or developing kind of finding in our bodies but not as high quality antibodies. Whatever the ultimate correlate or productions there's, there's importantly not been a head to head study of their inactivated vaccine versus m R N A vaccine.

[00:51:39]
But the general census generally consistent with what you said that they're probably less active than an M R in a vaccine. So yeah, the reason why I think, you know what the M R and a vaccine i think what happens with you is actually by going to do exactly what that m R S S and the M R N A says to make protein in this configuration with exactly, these nick, amino acids, and that's what happens.

[00:52:10]
And whereas with within inactivate vaccines, it's a little more broad from that standpoint and you've got potentially responses again, some of the other proteins happening as well, which may or may not be relevant. So to my knowledge, there's not in their current study that's looking at boosting inactivated vaccine with m R and a vaccine.

[00:52:37]
But I think that that's a great question. And I think that that's an important question for the world to sort out downstream. particularly if we can drop the cost of the M R in a technology such that could be more widely available. Thank you. Don't practice. Another question is from wendy, is in your slides, you said that liquid nanoparticles may cost the risk of allergic reaction.

[00:53:01]
What is the data and research about people who are allergic to food and, and run many factors? Yeah, so, so when we, if I go back to your slide so, So it's been seen is that there is a risk of anna for access with both emitter and pies or vaccines.

[00:53:25]
That risk is very, very low. So again, 2 and a half to 5 per 1000000, it's probably not different between the 2. Although, I think we'll certainly know more data about that. Over the course of time, from, from that standpoint. In many ways, a liquid nanoparticle is pretty inert because you've got the leopard, you've got then a few other things in it and one of them being polyethylene glycol, in particular, least in both emitter in advisor.

[00:53:58]
maxine, so that's kind of been the postulated reason for these and a flat agree reactions. And that's part of the reason that there's been a caution against if people do have issue with either peg or with points orbital, which I guess is chemically fairly similar, recommending against, you know, vaccine with m R N A vaccine in that setting.

[00:54:26]
It does not appear well the extent to which other other things might cross react, i think remains an open question. sorting out this issue I think will be important. Long term for the M R and a technology. And to the extent that that, that technology can more closely mirror the liquids and the appearance of what the body is seeing on a regular basis potentially could decrease that risk and get all kinds of instead or no questions.

[00:55:01]
Let's go ahead. I see just one was going In there are no questions. So let's thank sanderson, photos. presentation is a great presentation and thank you for answering so many questions. And on behalf of none of fans forum, i'd like to thank you for your coming and giving a presentation.

[00:55:22]
I'm ready, a busy schedule, and thank you for having me. Well, thank you everyone and we'll meet next Wednesday at 11 for our 3rd webinar. My proper sam different you'll have a great day.