Is the End in Sight? An Inside Look at the COVID-19 Vaccine and Approval Process

0:04 hello and thank you for joining us for this presentation and discussion on the covet 19 vaccine my name is 0:11 dubois bowman and i'm privileged to serve as dean of the university of michigan school of public health 0:16 the devastating impacts of the covet 19 pandemic have been felt around the globe 0:22 as the world turns its attention to the landscape of covet 19 vaccines and we're all collectively wondering is 0:29 the end of this pandemic finally in sight many open questions remain i'm honored 0:35 to introduce my colleague the world renowned epidemiologist dr arnold monto to help shed some light on what we know 0:42 about the vaccines joining dr monto today is dr emily martin an associate professor of 0:48 epidemiology at michigan public health and another colleague who's been working tirelessly to use her 0:54 expertise to protect the public's health throughout this pandemic in a year that has challenged all of us 1:01 in countless ways i've repeatedly said that the community of faculty staff and students 1:06 at the university of michigan school of public health gives me hope dr monto and dr martin are no exception 1:13 with that i'll turn it over to dr emily martin good afternoon and thank you for joining 1:20 us today for this important and timely webinar we are grateful for your participation today 1:26 and i'm sure you're all looking forward to hearing from our colleague the world-renowned epidemiologist dr arnold monto 1:32 so i'm going to keep my uh my early comments here brief through the event today you'll have the 1:37 opportunity to ask questions in the q a function the presentation will also be available for viewing on youtube after the session 1:44 my name is emily martin and i'm an associate professor of epidemiology at the university of michigan school of public health 1:50 today i'm honored to introduce dr monto the thomas francis collegiate professor of public health at the university of 1:57 michigan school of public health dr monto is the chair of the fda's vaccines and related biological products 2:04 advisory committee that handles covid19 vaccine reviews throughout his distinguished career 2:09 spanning seven decades dr manto has been involved in pandemic planning and emergency response to influenza and 2:16 other respiratory virus outbreaks including the 1968 hong kong influenza pandemic 2:21 avian influenza sars mirrors and of course the coronavirus pandemic 2:26 dr mundo was recruited to michigan public health in 1965 where he was he has worked closely with thomas 2:33 francis jr on the landmark tecumseh community health study dr manto expanded 2:39 the study scope to look at the spread of respiratory infections in the ten thousand residents of tecumseh 2:44 michigan and then during the 1968 influenza pandemic dr armando found that vaccinating 2:50 school-aged children reduced infection in the entire community in early demonstration of how herd 2:55 immunity works since then dr monto has been involved in evaluating a variety of strategies to 3:01 control influenza including vaccines antivirals but also other interventions that have become 3:07 all too familiar for us this year like social distancing and face masks 3:12 in the 2000s he was involved in developing pandemic control strategies leading to work at the world health 3:18 organization and in the us during the 2009 swine flu pandemic he's led clinical trials establishing 3:24 the superiority of inactivated vaccines compared to live attenuated vaccines for influenza 3:30 in 2010 dr monto established the household influenza vaccine evaluation or hive study 3:37 designed to allow the study of many aspects of respiratory virus infections over time 3:43 and this this study has provided the foundation for a continued study of coronaviruses 3:49 over time in 2017 dr monto is the plenary speaker 3:54 of an nih-lead workshop to develop a strategic plan and research agenda aimed at the development of a 4:00 universal influenza vaccine this work has formed the foundation of the now michigan influenza center 4:07 which launched as the pandemic was beginning these are just a few highlights from dr 4:13 mata's impressive and groundbreaking career and it's clear why he was selected to play a critical role in ensuring that we 4:19 have access to a safe and effective covid19 vaccine as soon as possible we at the university of michigan school 4:25 of public health are grateful for dr mata's leadership and expertise in these challenging times so without further ado i will turn it 4:32 over to dr mato for his presentation thank you so much emily and uh 4:38 i want to let everybody know that emily is the co-director of the michigan 4:46 influenza center as we go forward and we have decided not to 4:51 change the name because we still want to remind people that influenza is 4:57 a critical uh in what we uh what we are going to be looking at in 5:03 the future now emily mentioned the hive study and as we go into the 5:11 winter uh one of the things we saw when we did an analysis of the 5:17 coronaviruses uh back in the about eight months ago 5:23 was that we found that they were very seasonal now there were four seasonal coronaviruses and they uh 5:30 show up every winter and we wondered whether the seasonality of these viruses 5:37 was going to tell us something about the way uh sarsko v2 uh kov2 or the 5:44 kovid 19 was going to spread and uh i think we're beginning to sense 5:50 that what we are seeing now may in fact be a reflection of uh of of uh 5:58 uh of of uh this kind of seasonal spread now having introduced the need 6:06 because we know how badly we need uh vaccines and other pharmaceuticals to control 6:13 uh this infection let's start looking at what we're really supposed to be talking 6:18 about today and that is how we are going to be able to control 6:24 uh this pandemic through vaccines and uh we've all heard about operation 6:31 work speed and uh for those of us who don't have a background having watched star trek uh 6:38 this sounds uh kind of strange and suggests that there's undue speed associated with the 6:45 development and in fact that's not the case what is happening is that we are putting into 6:52 a one-year period what typically takes maybe 15 to 20 years 6:58 in terms of vaccine development and how are we doing that well we're working off platforms that 7:05 have been developed for other regions uh often for the original sars virus or for mers or for 7:12 other viruses to get things going we are also telescoping the studies uh 7:20 where we would have been doing things in in sequence and instead we're doing them in parallel 7:26 for example uh we would never think of manufacturing 7:31 and uh getting vaccines ready to go be before uh they were tested 7:38 and proven the reason this is happening is because 7:44 there's been a lot of attention to this and also a lot of uh funds 7:49 given to this effort so this is one of the major success stories of the response to the 7:56 pandemic so uh what i want to convince you of today 8:01 is that we are doing exactly what we ordinarily do with 8:08 vaccine development but on a shorter timeline now this 8:15 is an example of the kinds of things that are going on at the u.s level 8:22 in terms of trying to get the vaccines out quickly and it's basically a public-private 8:28 partnership and nih in particular and uh 8:33 is taking advantage of a lot of the networks that have been established to test 8:39 vaccines and that's why we've been able to do these very large studies that are currently underway or just 8:46 finishing on evaluating the efficacy of the vaccine this gives you a very broad picture 8:53 of what is going on they're taking networks for example that were testing hiv hiv vaccines 9:00 and other vaccines and in enlisting them to test the vaccines against covet 9:08 this is a much more careful look or uh look in detail at 9:15 the strategies and operational warf speed is uh between departments 9:23 of the federal government is the planning body for getting everything done including 9:30 distribution of vaccines to the states uh the active is the one 9:35 that we are going to be focusing more on today in terms of their activities the results 9:41 of these studies that are being put together mainly by nih and i'll go into this activity 9:49 in uh of active in greater detail and then we have the networks that are doing the studies 9:56 and this is what's going on in active and basically they are 10:01 harmonizing the efficacy trials they're putting together the networks to 10:07 do the studies and most importantly they have a 10:12 unified data and safety monitoring board that is looking at all of the studies 10:19 other than the pfizer study the pfizer study has their own independent data data safety and 10:25 monitoring board so whenever you hear something coming from there from from about about a hold or 10:32 something like that about safety uh or breaking codes or anything like that 10:38 it's coming from a single data safety and monitoring board uh 10:46 now why are we able to move so quickly and you've all read the press 10:52 uh about how successful the vaccine uh has been in early trials or 10:58 prelim in trials that where the code has been broken and it's because immunity 11:06 seems to be related to a specific protein the spike protein 11:12 which allows entry of this virus into the cells and we are indeed fortunate that this 11:20 uh spike protein was identified earlier in work with sars and mers 11:26 related coronavirus as the important component of the vaccine 11:31 so that development could move quickly and all of the vaccines that are being 11:37 developed whatever the platform whatever the way they have been produced are related to the 11:45 spike protein and that is the key to the strategy for vaccine control and 11:54 prevention now there are several different ways i've illustrated three different ways of 12:01 getting the body to produce antibodies and other and to respond in other word ways with 12:08 cellular immunity to this spike protein the moderna and pfizer 12:16 biontech strategy is to use mrna this is a genetic message 12:24 the astrazeneca and later jansen approach is to use a vector 12:31 to attach the genetic material of the spiked protein to an adenovirus 12:38 vector this is a virus which causes common colds 12:43 and other illnesses in humans and to not get antibody developed to that 12:50 they've used the chimpanzee had no virus and then we have another 12:55 system where we use a more traditional approach getting the protein of the 13:02 spike into the body through a new method 13:10 which is to make to get genetic material to make in cell culture the material 13:18 that is going to result in production of antibodies and other responses 13:24 and if you see sanity at the bottom this is very similar to what they are 13:31 doing for a licensed flu vaccine called flu block so these are different ways of getting 13:38 the spike in so the body can respond to the spike 13:43 protein and this is just a quick summary of all the ways that vaccines 13:51 can be produced why is rna taking the lead right now because it is 13:57 fast it's much faster than other methods because what you're doing is putting the 14:04 genetic material into the uh into the body and getting the body to respond and 14:12 we have non-replicating vectors which is the adenovirus related uh vectors 14:18 and then we have the protein the protein based which is the third method i was talking about and 14:26 that is slower and we are seeing this playing out in terms of 14:31 uh the timetable for vaccine availability now again this is the nucleic acid 14:41 vaccines and there's the rna at the bottom there and the rna is injected into the 14:49 uh into the muscle and it makes the body produce the viral protein to which the 14:55 body responds so it's all associated with producing 15:01 uh sars cov2 spike and getting the body to respond 15:09 and here's another paper showing the chimpanzee adenovirus if you look at the 15:15 top that's the code for the chimpanzee adenovirus and there is another 15:22 uh example of the method that is being used to get the 15:28 protein in through a spike nanoparticle again the spike keeps coming up that's the critical part 15:38 now why is this going so quickly and efficiently well we've 15:44 talked about the laboratory development of the product that's going to be delivered 15:49 uh there are have been standard assays of purity and lack of toxicity this is 15:55 standard for development of any vaccine but it's being done quickly and efficiently 16:02 because there's been a lot of resources given to it studies in small laboratory animals for 16:08 spike antibody production then in many cases injection 16:14 into non-human primates who were then challenged with the wild virus 16:19 and they've been protected and that gave everybody great confidence at move in moving ahead 16:27 to the large-scale studies that are being carried out phase one and phase two dose finding 16:34 to find the better dose because as i'll point out in just a minute 16:40 there's also been some issue of very ma of mild but uh clear uh side effects in terms of 16:49 aching and in some cases fever associated with these vaccines so you've 16:54 got to get the dose right now this is antibody and i'll go through this very quickly because 17:01 what's been remarkable about these vaccines is they all produce good antibody 17:08 to the sars cov2 spike and this is uh from the the this is from 17:14 the uh the pfizer vaccine mrna vaccine and here is another example and this is 17:22 a little easier to see and this is from the uh 17:27 this is from the the astrazeneca uh adenovirus victor vaccine 17:34 and you can see what's going on here and what you can also see is you don't get as good a response to a 17:41 single dose as you do from two doses so the tudo strategy has been 17:47 just about universally uh used we do think from some of the data 17:53 in the pfizer uh studies that you may get protection earlier before you get 17:59 the second dose but you're not as fully protected until you get the second dose 18:06 side effects there are mild acceptable side effects to these 18:12 vaccines if anybody has got the uh 18:18 [Music] the the the zoster vaccine the shingles vaccine you know that those are 18:25 reasonably reactogenic vaccines and you know that you've gotten them because you may have a little aching and fever 18:32 afterwards especially after the second dose these are adverse reactions to the mrna 18:38 vaccines and you can see the same kind of uh mild and moderate 18:44 reactions to the adenoviral vaccines and this is part of the dose finding so 18:50 you try to figure out what's tolerable in terms of side effects and what gives you the back best vaccine 18:58 response in terms of antibody safety assessments 19:03 we are very concerned about safety of course with anything that's new 19:09 that's anything that is using a novel platform which hasn't been 19:15 licensed before which is the case with the with with two of the three 19:20 approaches we've talked about and the only difference in safety 19:25 between what we're doing now and what is traditionally done is if we go 19:32 with emergency use we're only going to have the time period from the dosage to 19:39 uh the uh availability of the vaccine 19:45 to go on so we're going to have to keep watching there's no reason to think 19:51 that with this kind of efficacy that we're seeing we're going to have any safety problems 19:57 but as you go to larger numbers you have to have that in mind now the 20:04 you the uh collective uh dsmb data safety monitoring board did 20:11 see something with the astrazeneca vaccine and they put a cold on and that just 20:16 shows how well this has been done in terms of trying to 20:22 monitor the vaccine and how well it works now i'm going to use from now on some 20:30 power points that were led to me by the people at fda to tell you 20:37 about the licensure process at fda because i think that's a major 20:43 concern and i'll go through them rather rapidly to allow more time for discussion afterwards and this 20:51 powerpoint just says why we have to do clinical trials to be sure that we are 20:57 not deploying a weekly effective vaccine we want to do the best we want to have a 21:03 standard approach used now the efficacy endpoints that are being used and this 21:10 is from the guidance that fda issued what was being looked at is covid19 21:16 disease of any severity they could have used preventing severe disease they could 21:22 have used preventing asymptomatic infection but most have decided to use 21:27 covid disease of any severity and what they established as the endpoint 21:33 for approval would be greater than 50 efficacy not realizing that the efficacy was 21:41 going to be as high as has currently been seen and among the secondary endpoints was 21:49 going to be prevention of serious disease and again they thought that this would be 21:54 uh questionable and they put a lower bound of the confidence confidence interval at zero percent and 22:02 what we're going to see with the pfizer vaccines is that there was near 100 22:09 prevention of serious disease clinical trial populations have to 22:15 include racial and ethnic minorities this has been done and will be part of the reports that 22:23 everybody is going to see when we have our meeting uh next week 22:31 and the safety database needs to be large they say three thousand here well we've 22:37 got thirty thousand or forty thousand within these trials again money talks and the there have been a 22:45 lot of investments put on into vaccine development which has resulted 22:51 in large numbers of people being involved which has had a lot of so we have a lot 22:57 of data and not only do we have a lot of data we also have a great deal of uh 23:05 uh observations on clinical disease and that's one of the reasons we've got to this point 23:12 where we are able to look at emergency use very quickly 23:17 now emergency use originally they the the the the statements were 23:24 vague about when emergency use was going to be issued but what we can say now is 23:32 that they are using the same standards for efficacy 23:37 for emergency use authorization the only difference is that they we 23:44 are only having an average a median of two months 23:49 from the second dose so there's a shorter duration and what we're going to have to do is 23:56 watch what happens going forward there is no indication that we're going to have any surprises 24:03 but obviously you don't know what's going to happen as you go forward and safety monitoring 24:10 is going to continue whatever whether you have full licensure 24:17 emergency use authorization and cdc and fda are responsible for that 24:24 and we here with emily are going to be part of cdc studies following 24:32 the use of the vaccine in emergency use and then later on after full life 24:43 so we're going to be doing all of these things and following up with both licensure and 24:49 emergency use through observational studies now i'll just very quickly 24:57 talk about the vaccines related biological uh committee and i'm going to just uh 25:04 skip a few of these powerpoints just to allow more time for discussion and this 25:10 is the verb pack and the seed of the the uh 25:15 uh fda uses the verve pack in an advisory function they generally agree with the 25:23 recommendations of the rear pack and we held a meeting on october 22nd 25:29 to talk about the general principles of the vaccine approvals to agree that fda is setting these up 25:37 right in terms of emergency use and full licensure 25:42 and uh there was discussion about this and the issue was the two 25:49 months for emergency use and as i mentioned uh the question of 25:54 two months versus a longer period came up it was decided that given the fact 26:00 that we're in the mur at in an emergency that people are developing severe disease that needs to 26:07 be prevented uh that two months was a a reasonable 26:12 time to begin deployment of vaccines and uh there were discussions of the 26:19 primary endpoint should we be using more severe disease should we be using 26:25 asymptomatic infection and it was decided that the issue of asymptomatic infection could best be 26:32 handled in post-licensure studies or post-availability studies 26:38 because vaccines are rarely uh assessed in terms of how they prevent 26:46 asymptomatic infection and we but we need as we all know to get a handle on the role of 26:54 asymptomatic infection in transmission 26:59 pediatrics and this it was a little bit of a more complicated discussion 27:07 because we've seen some complications of infection of sars cov2 infection 27:13 in children so the vaccines may need to be evaluated a little differently as we 27:19 move into children so we do not expect very quick approval for children based on the 27:26 results in adults bridging studies so-called but there may need to be further studies in children 27:33 now we all are concerned about distribution of vaccines and that's not 27:40 what the verb pack does and yesterday the advisory committee on 27:46 immunization practice came up with recommendations for use of 27:52 the vaccine and this is a powerpoint from the verb from from the acip 28:01 at cdc how they make their decisions and this is a again 28:09 from the acip based on limited doses being available 28:16 and now we are told that these will be available to healthcare workers 28:21 who have direct contact with patients and then and also nursing home residents 28:28 and uh people who care for nursing home residents when larger doses are available then the 28:37 availability the the recommended target groups will be increased and then we will have 28:43 continued use so when we talk talk about the end game where we will be it will probably be in 28:52 uh late late uh late winter into the spring when larger 28:59 numbers of doses of vaccine are that are available and are 29:04 and can be administered and we can discuss that uh when we want to think about the end 29:10 game is the end in sight uh now 29:17 just in closing i want to let you know that our next meeting the meeting of the verpack 29:23 is on december 10th this will be specifically to review the 29:29 pfizer vaccine for emergency use authorization this is the 29:35 web page that you can access and as the previous 29:41 meeting was on uh live on youtube this meeting will be on live on youtube and unfortunately 29:50 for me uh sitting his chair it's going to go from 9 00 am to 6 pm i hope we can finish early 29:58 but what you're going to be able to find on december 8th is the report from pfizer the complete 30:05 report from pfizer on the attached to the web page so you can see 30:10 how the vaccine has done and how well it has prevented and the safety 30:16 data so nothing is being hidden this is all an open transparent process 30:25 and uh thank you all for listening and uh i look forward to a robust 30:31 discussion thank you arnold um wonderful presentation so uh before we get into a discussion now 30:37 arnold and i can debate vaccines and cove everything covet and restore viruses 30:42 um from now until two o'clock but we want to see everybody else's questions so at the bottom of your screen there is an 30:49 option to choose the q and a function and there is where you can put questions in there people will be 30:55 watching and we'll i'll i'll be watching for questions that we can add 31:00 um to to primary discussions so 31:05 arnold are you ready for i am ready all right first question so you know there's been 31:11 a lot of discussion especially following the acip um meeting yesterday 31:17 about prioritized groups for vaccination who's going to get the vaccination when but there's a lot of people that 31:23 aren't um seeing themselves discussed in those conversations right because we're talking about who the first 31:29 batch of vaccines are going to come on but what would be your best guess for people that aren't in the priority 31:34 groups the first priority groups in terms of when they could see a vaccination so people like a healthy 65 year old 31:43 a healthy 30 year old where where's your guess in terms of when that's actually going to be available well 31:49 i think we all are working from the same uh information 31:57 availability on in which is basically in the media what whereas there's a great deal of 32:06 transparency about the fda process there's been less transparency because there are 32:12 commercial considerations about the availability of doses 32:18 and one of the things that people don't realize is that this is a public private 32:24 partnership and when fda looks at this they look at this as pfizer making an 32:31 application for a vaccine for the same reason 32:37 there are issues about figuring out how many doses are going to be available 32:42 and how many vaccines are going to be approved by that time because we know that modern is coming 32:49 along they're going to be discussed on december 17th and then the next one's probably going 32:56 to be astrazeneca uh but there have been some issues that have been in the media 33:02 it's hard to judge that my best guess is that it's going to be into the 33:10 late winter early spring be before we're going to have enough doses available because this is going to be driven by 33:16 the number of doses available along those lines with um in terms of 33:22 um the way the trials have gone um and in the speed with which the the fact that we're kind of 33:28 compiling all the questions for vaccine trial into one big trial for every product um what kind of safety what does this 33:35 mean for safety and efficacy data for populations where there would typically be a special trial 33:41 just for this population so one big example is pregnant people we typically would have a trial just for pregnant people um what is what 33:47 does this strategy mean for safety and efficacy data well i'm not sure that there's really 33:54 typically a trial in pregnant women for most vaccines in fact most vaccines 34:02 are are used in pregnant women on the basis of observational studies 34:10 and part of that is because the companies typically do these trials and they're terribly concerned about 34:17 liability as they do studies in pregnant women the most recent studies that we've seen in 34:23 pregnant women and this is relatively unique are rsv and influenza trials as you well know 34:29 being directed to pregnant women often to see if it protects their 34:34 offspring against the particular uh illness 34:40 we are recommending vaccine for pregnant women for flu a high priority at wbho 34:48 on the basis of mainly observational studies and you and i do observational studies 34:54 together so we are convinced that we can learn a lot from observational studies 35:00 and i think as we go forward with these covet vaccines given the fact that nobody wants to will 35:08 want to be in a placebo group anymore we're going to have to rely on observational studies and good 35:14 observational studies to give us the information we need yeah and i wonder i wonder how much the 35:20 world is expecting how important observational studies are about to become 35:26 better because nobody we can't export our studies yeah 35:32 yeah once once we've got what once we we we uh what and and this will apply to 35:38 any improved vaccines these this this is the first generation 35:43 of covet vaccines we may have improved vaccines come up later on and how do you study those yeah you're 35:50 going to have to study them in comparative trials and observationally and how are you 35:57 going to be able to say which vaccine gives you longer protection that's going to be again observational 36:04 data it's going to look like the last couple of years of flu vaccine where you have all these different products on the 36:09 market and you're trying to figure out which one you know everybody's trying to figure out which one should they drive 36:14 to to this can get that vaccine or that pharmacy and get that there's no incentive for companies to 36:20 to do this unless they've they're really convinced that they can make money and that their 36:25 vaccine will prove superior yeah i'm gonna um i'm gonna bring up a 36:32 question that's a little bit um on a little bit of a different topic now as you know so there's been a lot of 36:38 a lot of papers particularly recently on changes in the virus and genetics 36:44 genetic changes in the virus um and so question freeze what do you think is that going to have any impact 36:50 on vaccine effectiveness like we're so used to hearing with influenza vaccine effectiveness being impacted by 36:55 changing the virus so one is that going to matter and two to what degree are we paying attention to 37:02 other elements of that of the virus besides that one kind of spike 37:09 site that we're mostly paying attention to well the first one's relatively easy and 37:15 as you well know because we have our colleague adam laurin who's doing the sequencing with us uh 37:22 and uh while the virus is changing somewhat it's not changing enough to 37:30 escape from antibody produced to the uh the to the the virus that's uh 37:38 messaged in the vaccine uh whether that's gonna last who knows the positive 37:47 is that we have been living with four seasonal coronaviruses which cause common colds 37:55 and those viruses have been just about the same for the 50 years i've been involved in 38:01 studying them so we can still see the same genes associated with those 38:09 viruses that produce antibodies that's the good news the bad news is that we do see 38:16 reinfection with these viruses and uh we need to figure out what the 38:22 correlates of protection are because people have a lot of antibody 38:27 to the spike of these viruses so first things first we can 38:35 stop the pandemic through use of the current vaccines and through unfortunately the herd 38:42 immunity that's building up because of bad behavior bad behavior may 38:48 be having good results in terms of getting natural infections producing antibody in 38:54 the population which didn't happen last spring and that combined 39:00 with a vaccine is going to result i would predict in a decrease in transmission in our 39:06 populations and then we have to worry about improved vaccines 39:12 drift all sorts of things but we are indeed fortunate that the path to 39:18 these vaccines was easy from a scientific standpoint 39:26 much easier than an hiv vaccine remember they've been working on that for how many years it's been 10 years away 39:33 for a very long time exactly and uh and and and 39:39 and also because of the resources that have been given to make people to to to 39:46 uh de-risk the the whole operation you they've de-risked 39:52 companies and taken away any kind of liability 39:57 and that that's in our society that's what you need to get 40:02 to get them to uh to really move ahead quickly and it's um you know i've seen some 40:09 questions come through about um how how can we assess duration of protection especially given 40:15 that um and that's going to be i mean i think you've it's sort of where the observational studies come in that we're going to have to be 40:21 watching carefully um how long infection or how long protection continues 40:27 after all of these vaccines are administered even outside of clinical trials right and that and and that will be 40:34 relatively easy as long as we can get as we as you and i both know the data on 40:40 who got what vaccines and things like that that's going to be the hardest thing my 40:46 concern is that a lot of effort we've warped speed speeded vaccine development 40:54 we haven't put the same kind of resources into deployment and follow-up and we're going to need a 41:01 lot of a lot of attention given to this to answer the critical questions that 41:07 everybody wants to know that you can't learn uh from the clinical trials even if they 41:13 involve 50 to 60 000 people you're not going to learn everything in that kind of 41:20 population when you're giving the vaccine to millions yeah and i think one of the big 41:26 questions that's going to come up as this gets deployed is you know now that we're starting to see reports 41:31 um about reinfection which we know happens with the seasonal coronaviruses and we've seen reinfection with the 41:37 other coronaviruses as we're starting to see cases of reinfection with this how does that interplay with vaccination 41:44 and um particularly how does that help us answer people who are you so we usually tell people that had 41:51 coveted already if you've had it in the last 90 days you don't need to get tested you're probably protected for a little while 41:57 but should we be also vaccinating those people because of that 42:02 potential for reinfection what do you what's your opinion on that my answer would be yes but lower in the priority 42:08 scheme and the reason i say that is paradoxically the antibody being produced by these 42:15 vaccines is better than what's been seen in 42:20 people who have recovered from covet whether that and also as you and i 42:26 both know that there are some weird things about asymptomatic infection mild infection 42:33 not producing the kind of antibody titer that you see in severe infection which 42:39 is something we usually don't think of so my answer to that is yes they should be vaccinated 42:46 but since they certainly have partial protection they are lower down on the priority list 42:52 than uh than others who have not been previously infected yeah this reminds me 42:59 of when we did um a seminar in january and we got asked about vaccination we said a vaccination 43:05 was going to have to beat nature because the vaccination would have to be better than natural immunity to a coronavirus in and 43:13 we're not used to seeing that not used to that this is a 43:18 i keep coming back to calling this a weird virus it's weird in so many ways the disease that causes 43:25 the kind of transmission we saw in the spring and even now the transmission when 43:31 you're exposed some peop some households will transmit to everybody and some households will be 43:37 practically no transmission and we have super spreaders and non-spreaders and with flu we're much more 43:45 we can always predict it'll spread with this who knows yeah absolutely 43:51 can we talk a bit more about side effects and particularly side effects as they pertain to the fact 43:58 that we've got all these different types of platforms i mean are these are the side effects 44:03 coming out of the trials primarily like injection site a couple of days or are they long-term side 44:10 effects that are being seen well they're not not long-term side effects i i think and interestingly 44:17 they seem to be associated more at least with some of the vaccines with the second shot than the first shot i 44:25 think the interesting thing will be to see if when people give the baculovirus express 44:32 vaccine the protein vaccines which are a lot more traditional in 44:37 terms of not including genetic messages and and and different platforms adenovirus 44:45 is getting in there it's even though it's not replicating it's still doing things to t cells 44:53 what happens when we start going with those other vaccines is it a function in other words of the 45:00 of of the spike protein that's attached or is it a function of the platform 45:06 that's being used we really don't know that yet yeah and i think you know as we think 45:11 about different platforms there's a question about and i've seen a couple of questions with this theme of 45:17 when do you choose one versus if you have a choice between multiple vaccines which product should you choose 45:22 are we going to know and i mean my viewpoint on this is that you know we see this with influenza vaccines you 45:28 you choose the one that's right there and i think with the distribution and the production challenges i i wonder 45:34 if what we're going to see is different products being deployed to different populations different places but me as an individual i'm not going to say 45:41 i have my choices between a b and c at least in the early days and then you have the minus 45:47 the minus 70 centigrade issue yeah which is going to limit distribution of 45:52 the pfizer vaccine and i wonder what kind of future that vaccine is going to have 45:58 as other vaccines emerge and are easily more easily administered yeah yearly will have an effect in 46:06 much of the rest of the world we we look at some of our rural areas 46:11 but you have most where most of the population of the world lives there's no way 46:17 a vaccine like the pfizer vaccine can be administered there yeah absolutely and then you know it's 46:22 nice to see that the pfizer and the modern vaccines both have similar i mean their their efficacy is 46:28 around the same range but if these other products come up with a different range of their efficacy then 46:34 we're gonna have to figure out where we prioritize the more potent vaccines versus not and it's kind of what we do with flu vaccine 46:40 right we prioritize accidents for certain arguments okay and but but 46:45 but the other thing is let's hope enough people are given these other platform 46:51 vaccines because they may last longer you may get a longer duration of immunity 46:58 that's a good point it may be up and back and that's why this is also important 47:04 because under emergency use authorization it's a median of two months in terms of safety it's also a 47:12 median of two months in terms of efficacy so this is they're very efficacious 47:18 right after they're administered yeah knows what happens long term it 47:23 means you can't wait too long to get through a group of people too you got to really get vaccine out there but the need is there 47:31 so then that's the rationale for the emergency use yeah um all right changing topics again 47:38 slightly what are we gonna do about the kids and the teens having uh having an almost team in the 47:44 off in the office next to me that would really like to go back to well i'm not sure where this emergency use will end 47:52 in terms of age some of the studies have been done down 47:58 to 12 years of age they have not been done in younger children and 48:06 as you well know it's the teens that have been getting infected and some 48:11 of them have been getting sick so i would predict that as we go forward 48:18 we may well slowly use the vaccines in older children and 48:26 then before we go to younger children because it's the younger children mainly 48:31 that have we've seen this misc the multi-system 48:36 inflammatory syndrome occurring with infection and that's with infection so who knows 48:43 what happens if you give a vaccine and there it may make a difference if you give a 48:49 genetic genetic material versus protein yeah to what i mean i think there are some 48:56 pediatric there are some pediatric trials going on now i think the 49:02 pediatric trials really have taken uh have been put on the back burner in 49:08 terms of of prioritization they're not they they don't have nih 49:15 pushing them the way and using all the networks yeah do you think that was because 49:21 i think this is that this is in part of the concern about moving too fast and 49:26 short do you think that maybe the early the kind of the early viewpoints that children 49:31 weren't getting infected when it might have just been an epidemiologic phenomenon um but i think that may have also maybe 49:38 set the stage for moving slower in children it it did but at the advisory if there was 49:45 any pushback about anything it was about children's studies from the 49:50 pediatricians in the group they felt that through the traditional 49:56 approach of just using bridging studies relatively small numbers of studies in 50:01 children using production of antibody as the outcome rather than looking at 50:10 clinical protection of the rest which you can't get in relatively small studies 50:16 should not be used that larger studies should be carried out and of course as 50:22 pediatricians they said we should be doing and i'm sure we will 50:27 yeah but the question is when right so um i think we have just a couple of 50:34 minutes left i'm gonna ask you one more question and then um let's see if there's anything else that we want to 50:40 say before we close up but um so one of the things that i think you 50:45 know we're so i think the american public is so used to flu vaccine campaigns and flu vaccine campaigns are so centered 50:51 around the one dose strategy where you just find people wherever you can find them and you give them a dose and 50:57 they're good for the season well depending on how effective the flu vaccine is that year well we hope it works 51:03 this is a two dose strategy which is operationally fundamentally different in how we think about things especially when you have 51:10 multiple products and i we want to get product a and then get product a again 51:16 um so can you kind of explain for the audience why why there's why are we even going 51:22 down this road why is there a two district i know you touched on it in your presentation but why are two doses important 51:28 well two doses seem to be much more protective than one dose some of the studies 51:35 may show and they are looking at people who were infected during the clinical 51:43 trials after the first dose and we may see whether prote there is some level of 51:50 protection uh right now all of the data 51:55 are for the two dose strategy so it is important for people 52:01 to get the second dose and for health care providers to know what the first dose was so that they 52:08 could give the right second dose unless we have regional 52:14 differences so everybody in one region because of availability it's getting one vaccine 52:20 in some other areas they're getting another vaccine uh but that that's where we are now 52:27 we just have to remember we didn't even have the sequence of this virus 52:33 until january 2020 when the chinese let us have it 52:40 after not half and i won't go any further than that but that was one of the first 52:47 things we got around the 20th uh or so of january last uh in 2020. look how far we've gone 52:56 since we've got that sequence it's incredible all right so given so given that um 53:04 that if a vaccine when a vaccine is available for you are you going to get it and does that 53:10 answer depend on which vaccine it won't depend on which vaccine 53:17 i will get it but since i've been happily living not going outside i want to be sure that 53:25 those people who are more at risk get it first 53:32 and then i will happily get the vaccine i think what we've seen is 53:39 much more encouraging and you can tell how encouraging this is because of the 53:45 50 percent positivity that was set in the cdc in 53:50 the fda guidance and having this as at greater than 90 53:57 percent at least from the preliminary reports really changes everything and it should 54:04 change people's attitudes and it certainly should make p 54:10 and and and they really haven't seen severe disease in anybody who has been vaccinated now 54:18 that may not continue because the most vulnerable they've gone to older people but they 54:24 haven't gone to the most vulnerable and some of these people may actually because of co-morbid conditions than the 54:31 rest have severe disease but that sure is encouraging and i think that we should 54:39 move ahead and get vaccinated when it's our our turn to get vaccinated 54:47 because because i think this is being looked at very carefully 54:52 and let's help let's hope our our local authorities who are going to 54:58 be under tremendous strain when they're into handling the pandemic 55:04 and now also trying to organize the distribution of vaccine 55:09 support them as best we can well it's definitely i agree it might my turn is going to come later than your turn but i'll 55:16 definitely give it as my turn but i will um i think i might still use grocery delivery even 55:22 after i get it because i'm i'm becoming used to not going to the grocery store and i enjoy it well my dear wife is in the other cafe 55:31 she does not enjoy not being able to go into the grocery and and pick out exactly what she wants so 55:38 we have a we have one of our few diversions in opinion on that one yeah so when 55:45 when are given all of this with the vaccine landscape and all the distribution things um when do you you know this is a 55:51 combination of both vaccine and this idea of vaccine driven hurt immunity when do you 55:56 think life is going to feel normal again or are we sort of forever changed as a society and how we interact with people 56:02 well i'm not going to go into the socioeconomic considerations whether 56:09 big office buildings will ever be filled the way they have been in the past whether some of the things that we've 56:15 done have changed i'll just tell you my own view 56:21 that it's so much more efficient when you and i are down the hall from each 56:26 other and getting things done that having to communicate the way we're communicating now 56:32 and i think i think we'll be back to that level probably if not in the middle of the 56:39 spring probably by early summer because i think we're going to see seasonality i think we're good 56:44 it's going to be much more like a behaved like like flu outbreaks which behave 56:51 themselves this one has not behaved itself i was surprised we had as much 56:57 transmission over the summer as we did and it's probably because we had nobody immune 57:02 so we're going to have a lot of people immune we may not ever see stopping of transmission 57:10 at least uh in the middle of the winter but things are going to go be a lot more 57:16 like normal uh by the time we get into warm weather i hope so 57:21 all right well with that um i am going to close today's session on that note um 57:28 thank you again arnold for the presentation and the conversation uh a link to this recording is going to 57:34 be shared with all registrants and it's also going to be posted on the school of public health website it's 57:40 going to be posted on youtube for viewing and sharing later and it's going to be available on the school of public 57:45 health social media platforms so please share widely and get this information out there 57:52 thanks everybody for submitting your great questions and engaging and thanks for coming to the talk today