TWiV 802: Another epitope with Shane Crotty

this week in virology the podcast about viruses the kind that make you sick [Music] from microbetv this is twiv this week in virology episode 802 recorded on september 7th 2021 i'm vincent draconiello and you're listening to the podcast all about viruses joining me today from ann arbor kathy spindler hi everybody here is 82 fahrenheit and we know that 82 is 28 in celsius that's true and uh it's sunny and we have some uh nice clouds uh we're we're not that warm we're 25 c but nice blue skies very nice also joining us from austin texas rich condit hi everybody 89 degrees partly sunny you know texas texas it's a little cooler than last week you were in the night yeah we're uh we're uh we're on our way out of this nonsense [Laughter] [Music] i think ann from madison new jersey brianne barker hi great to be here um same weather as vincent i know no one's surprised but it is beautiful out there very nice day yep beautiful day our guest today is coming back i think for the third time he is from the la jolla institute for immunology shane crowdy welcome back hi everybody thanks for having me yeah the weather here is uh san diego weather what is it 72 in sunny right yeah do you get tired of that no [Laughter] somebody asked me on a podcast the other day whether i preferred florida or texas weather and i said san diego yeah well i mean san diego is has gone through the austin growth right san diego's has grown for years it's huge and austin is just trying to be that way yeah all right do you want to do your psa before we get started kathy sure just to remind everybody that asv is still sponsoring town halls about vaccine education go to asv.org education and you should tell your friends and your family and your colleagues about this if they have questions about the vaccines we have experts from asv who are there to talk about them answering the questions and a few of them upcoming are in spanish again so those are pretty popular as well so asv.org education all right so sean i think you were blast on last summer uh and a lot's happened so i thought i just looked it up and it was november that summer here in new york really it's november sorry i think the first one was last summer which which uh which i know a lot of people actually tell me they remember that one so that was pretty good and then i think i came on maybe late november for whatever okay 22nd 20 years that would have been uh our coveted memory study was public at that point and was uh okay well november seems like years ago so it does seem like yeah yeah seems like last summer and and then since then we had alessandro on as well after you so uh now we're circling back we we uh we get a lot of requests for you guys so here you are by the way i have for the um listening audience uh i have discovered that well everybody who's listened for a while understands that you can't understand the content of an episode from the title okay right uh and so uh trying to search for an episode could become problematic but i've discovered that if you type twiv and then whatever thing it is you're interested in you get a pretty good yeah that's true probably you know yeah like if you uh uh type twiv karate you'll get all of um shane's past episodes yes i do the same i learned a long time ago to do that yep twiv and whatever and you get what because there's nothing there are no other twivs or very few others to to confound it if there are there on the page 10. all right so uh shane i wanted to just go through a bunch of uh topics that have changed since we last talked and um i mean one one of them of course is boosters but we'll get to that in a bit but i find there's a lot of discussion about immunity after x after natural infection after vaccination after infection and vaccination after vaccination and infection so let's try and get through some of those let's start with immunity after natural infection give us a sense you know antibodies t cells breath longevity etc yeah sure um so what we reported was that after a natural infection looking eight months out people generally have t-cell memory b-cell memory and antibodies um and that the kinetics of those look like they would probably be maintained for multiple years and i'd say there are multiple other groups that had nice studies about individual pieces of that so we did antibodies cd4 cd8s and memory b cells and a number of labs confirmed individual pieces of that and then i'd say that rafi ahmed and julie mackerath had a really nice follow-up where they did all those things and they did different statistical modeling uh and so from their statistical modeling they were predicting uh also that yes you should have t cell memory and b cell memory and antibodies for for years um into the future and that it was stabilizing around six months sort of you know so what you saw between six months and 12 months was was probably pretty predictive of of what you might have for for a number of years which immunologically fits with with some other things that we've known and so that's that's made sense um and that the t cell response is broad and that the memory b cells have high quality which i can come back to because that connects to the natural immunity plus vaccination and what does that immunity look like which which i've called which i call hybrid immunity other people refer to as bulletproof or you know some other some other phrases but i go with hybrid immunity you know a mixture of two things um can you talk a little about the alternative solution so yeah so there's a lot of heterogeneity with natural immunity and so that's one thing that that we certainly pointed out that was quite striking that between two different people essentially any two different people you could have a hundred fold up to 100 fold difference in memory b cells or t cell memory or antibody levels and that those didn't all correlate it wasn't that the person with low antibodies necessarily had low t cells or memory b cells they were they were largely independent and so you know one of the things that we've said is that that's one really good reason to get vaccinated you know that heterogeneity isn't it's not as consistent of immunity as you would expect for a vaccine and so you know if you had a basketball game right and one person scored one point and the other person scored 100 points right you would not consider those similar outcomes and it's not that immunity is the same thing as a basketball game but you know those are those are big numerical differences and there have been a wide range of real world studies trying to follow how good is you know natural immunity and i'd say most of them have have found natural immunity has a significant amount of protection but generally a little less than what than what the vaccines give over let's say that six to eight months window of time that's what that's what most of them have have reported out and and when i most frequently get asked well why is it somebody who's had who's previously been infected right why should they get vaccinated my normal answer is really variance that it's been less clear how good natural immunity is against variants usually people with natural immunity don't have antibodies that recognize variants as well as as as vaccinated individuals and and really the big manaos outbreak you know the gamma outbreak indicated that the people with natural immunity probably weren't doing so well right because the implications were there were so many people got infected the first wave but it seems like they were getting reinfected in the second wave and so that the protection from natural immunity at least against that variant didn't look as good as you would like it to be whereas just to go and step to it with the hybrid immunity so people who have been previously infected whether it was asymptomatic symptomatic hospitalized or whatever if they get you know one dose of an rna covalent vaccine their antibody titers are a hundred times higher uh against variants than than what they had you know the day before they got vaccinated and that they just have better breath against every variant anybody's ever seen right they can even neutralize original sars right that's how good their breath gets with just a with just a single one and that looks like that's because that connects back to after the infection they generate such good t cell memory and memory b cells that then when they get one dose of that vaccine that whole library of interesting memory b cells gets reactivated to make all these interesting antibodies that they had they basically had as a library so that's yeah that's that's it in a nutshell i would say for those two so so i i have two other questions about natural infection um one of them is that i think that sometimes people like to try to make comparisons um between the immune responses that we see to different viruses um and so when you look at this response to sars kobe 2 can you sort of say that it looks similar to what we see with other infections does it look very unique or is it sort of look like same old same old yeah great question essentially as far as we can tell it looks like a normal immune response to a respiratory virus infection that was you know gonna give you flu-like symptoms you know and and actually pretty not too unlike what uh some some live viral vaccines have even given you surprisingly when we tried to do the head-to-head comparisons when we tried to compare to the literature we actually found that there's really not many reference points for we said all right we measured t cell memory and memory b cells for eight months right in people after sargon's code v2 infection how does that compare to other infections and honestly nobody done it before so that was the largest study ever of immune memory over that kind of time window for any viral infection that actually had you know longitudinal data so the bits and pieces we could find was really yellow fever virus data from from the vaccine honestly from rafael and the memory t cells look basically basically as good after a sars2 infection as they do against a yellow fever vaccination so that's a pretty strong you know reference point and then from memory b cells there were about i think half a dozen people that laura walker studied with yellow fever vaccine actually again and actually looked kind of similar you know in terms of number and quantity so overall it looked yeah it looked good but we didn't have as many benchmarks as we would have liked yeah and my other question is about compartmentalization um so you know most of what you are showing here is blood um do you have any uh kind of thoughts about whether you see kind of that same great mucosal protection same great memory protection in the mucosal surfaces or things like that yeah that that's absolutely the biggest gap in knowledge still is you know it's absolutely appropriate for somebody when you know when talking about immunity to say look it's like real estate right location location location um where is it and and for vaccines you know we can basically say uh look location matters but for lots of things when you generate that circulating immunity right that immunity in the blood um it can get to where it needs to get in a reasonable amount of time and that looks to be that's that's been the case i think for for service coffee too and that what you talk about the most with the vaccines right is can they prevent the hospitalizations and deaths and all of that's about lung infection and you know hospitalization numbers we talk about or hospitalizations like day 21 that's a really long time after you've been infected and so there are weeks for the the cells to get to the right place and do the right thing and i'm sure they get to the right place and they're doing something useful at least by day six you know and so the fact that it's circulating and not not at all not at the portal of entry is okay for those metrics but for natural immunity yeah there's going to be more of a bi we would expect more of a bias in location um but there hasn't been um there's still a knowledge gap there there's some data on antibodies you know that they're that they're measurable and particularly in saliva which is easier to to get samples from than the nose saliva data out for like six months post-infection but it's it's still a real gap i wish we had better data so what about um [Music] after vaccination only how does that compare with natural infection in terms of longevity and and breath and you've looked at mrna vaccines right yeah so yeah so the first available data was for a modern vaccine really done by the nih group and uh seeing that six months out from the in the clinical trials they definitely still had antibodies and it was about a five-fold to tenfold decline depending on which number you use which is a significant decline and so then the question really kind of becomes is it stabilizing around six months you know is it going to be pretty similar 12 months are you going to continue that that type of decline um and so we we were the first to report t cell memory for an rna vaccine which which was uh med archive maybe six weeks ago and we actually did it for the 25 microgram modern vaccine the low-dose modern vaccine and we thought well with the low-dose vaccine that's actually kind of a higher bar you know did you actually generate good memory after even if you got a lower dose of the vaccine and we were actually really impressed that there was uh the t-cell memory was quite stable out to six months after the second dose so seven months overall so six months out from the second dose and there was only a twofold decline from peak for the t cells it looks you know it looks quite stable looks like it would last for four years which again we were really impressed by because it really hadn't ever been on a vaccine data like that we were worried that maybe it didn't generate good memory it looks like it generates uh great memory both for the cd4s and the cd8s and john weary's now got a really nice pre-print out where they've looked predominantly in pfizer vaccine and they see good t cell memory and good memory b cells and so overall to me it looks like the rna vaccines are generating quite good immune memory um a good quality good magnitude of memory b cells cd4s and cd8s and so i would expect that would mean and uh ali ali betty published it that he could see long-lived plasma cells after uh vaccination so there's at least some long-term antibody production that's going to go on so i would expect antibodies to kind of stabilize you know between 6 and 12 months given the quality of the other uh the other memory um yeah i guess i'll pause there so i'm asking this question mostly because a lot of people ask this question of me um and i want to you know kind of see what you think for the answer as well um so with that response to vaccine um how much variation do you think that you might see um when varying the interval between the first and the second dose would that make a big difference in the big picture would it make difference in the details you know what what do you speculate you might see there yeah so so that's actually a topic that we research actively in in vaccine immunology uh you know it's actually something in the hiv vaccine field that i that i pushed on like five years ago that that essentially all the monkey immunization studies it was basically vaccinate repeatedly as fast as you could and vaccinated as many times as you could you know and i actually pushed to say look what's lacking here is quality in the immune response and and quality is a different process and it can take some time and so let's let's try and give the immune system some more time between immunizations for for developing quality and really that would be from a t cell side giving them a chance to rest which is kind of uh classic work from rafael's lab and others that the t-cells enjoy a bit of rest before seeing anagen again to give best quality memory and on the antibody side it's really about the germinal centers that the germinal centers can go on for quite a while after the the immunization is over and it's in those general centers that you're getting this real-time evolution right an increase of antibody quality and competition between the different b cells and antibodies and it's unclear what happens when you reimmunize you might you might actually be shutting off all those journal center reactions so whatever was going on you've now basically truncated it and told it to start over sort of thing and so he said look just let's let's try and be patient basically it's really hard to be patient but let's give it a chance and so when we spaced things out to eight weeks instead of four weeks um we actually started getting better much better neutralizing antibody responses in the monkeys than than in four weeks and we've been exploring that even further now and in work that we've got preliminary data on it and that was the hiv studies sorry that was hiv studies so you know we said look for covet 19 you know when people were saying hey i got my first dose of moderna and i missed my appointment right and so people might i i miss my four week appointment you know am i done you know can i am i am i outside of my window of opportunity am i stuck with the one dose and the other no no no that's not it at all it's that four weeks is the fastest you could get that second dose you know it's like get it six weeks get it in eight weeks and and i said even you know back in december i was like your immune response would be at least as good um if you've gone six or eight weeks as four weeks and probably better than four weeks the moderna and pfizer were making decisions based on what's the fastest it's a pandemic what's the fastest we can possibly immunize people and give them protection right not we've got a year right what's the optimal most patient way to do it and so uh yeah i think i i think it'll be really valuable to see different timings done and see what what the data are the clearest data so far has been from one english study that compared pfizer three-week divisor shoot i can't remember if it was eight or twelve week um uh and what they saw was the the delayed boost um gave two-fold better neutralizing antibody titers but i actually gave a little worse t cells by their gave about two fold less t cells by the acids that they used and so um yeah i think it i think it needs some additional study and i definitely think the timing intervals matter which is one reason people have talked about boosters you know to say look what you got done early was things you could get done fast but giving your body six months and then coming back there's some immunological value in that now if you don't without any boosting how long would germinal center maturation continue do we know that vincent is a fantastic question and we've we've been working hard to answer it so in mice it's generally like a 14 to 21 day process if that's an average general center and then if you get really good ones it could go like 28 days but in monkeys when we started doing these hiv studies we we said look we just don't know because journal centers only occur in lymph nodes they don't occur in blood and so you know 99 of the time you measure what comes out in blood and you're you're just guessing and so we said it so we started using uh an actual clinical technique uh lymph node needle aspirates where we would immunize the monkeys like in the shoulder say and then you know the lymph node that becomes reactive is the armpit lymph node the accelerator that's so you can actually insert a small needle into that lymph node and just siphon off a small number of cells and just see other germinal centers and we started doing that and it was really valuable and you can go back and you can do it longitudinally so when we did that we actually saw they would be having germinal centers for eight weeks eight weeks or more and it was in those animals that they got really good neutralizing antibody responses uh yeah so those are things that we know and then uh ali ali betty at washu has used that same technique now in humans uh with people getting the pfizer vaccine and he saw evidence of general centers at least out at 10 weeks in some of those people handful of people but you know yeah but you said earlier that infection followed by vaccination you get a basically a better response how about i mean to me that sounds mostly like okay it's a boost okay so what happens if you get infected twice do you know yeah i haven't seen any study on on that it's a great question um for me you'd have to break that out into the type of infection right because the number of those are people who got basically an asymptomatic infection first and then and then they got a systematic infection second [Music] and so maybe they just didn't generate much the first time around but yeah it'd be good to see i think i can't even remember if i've seen a case study on that i've seen antibody case studies that that that they certainly get an antibody boost uh you know n equals one type stuff um i don't think i've seen any t cell data so i want to uh clarify or try to clarify something else up on top and that is the role of the different types of immunity antibody humeral versus cellular uh you have a statement in one of your papers this is the uh never mind it's in one of your papers while it is not anticipated that circulating memory t cells would be effective in preventing sarge cov2 infection it is plausible that they can contribute in reducing covet 19 severity so you're making a distinction between the arms of the immune system and its role in infection and severity so uh i i'd be interested in you elaborating on what you're thinking how you define how you distinguish between infection and severity and how you think the different arms of the immune response play into those processes yeah sure boy vincent do you ever show slides in this i actually have yeah you can show you can share your screen sure i wasn't planning on it but i literally have it on my screen and i was saying this to the who on friday so um all right let's do it um [Music] there we go just go um yeah i mean i basically let's see i'll do it i'll do it so well you'll like this i always start with the virology i was like look the the parts of your immune system that can contribute to protection depend on the nature of the disease right how fast this disease and where is it and in this case we've got a virus that's really fast at replicating right in nasal spaces and oral spaces so within four days you're at a point where you can transmit to other people and you're symptomatic at day six right and it's a race race between the virus and your immune system but the serious disease is all about the lungs uh that's when you get the pneumonia that's where you get the hospitalization and that's where you get the death and and for hospitalizations you know we always talk about hospitalization numbers at day 21 because it's actually a slow infection in terms of getting that lung infection and getting to severity that would result in in hospitalization so you basically got fast infection in these two tissues and slow infection here and then you've got this spectrum of symptoms right and so the the nasal oral that's your asymptomatic posse symptomatic cold like and even and even flu-like and really it's the lung infection that are your hospitalizations icu and fatal cases okay and so um so with that in mind what's the immunology uh well the immunology is uh antibodies are your first line of defense period right so if if you can have so much antibody present that you can stop the virus right sterilizing immunity that's all you need that first line of defense is is all you need and so if you're trying to prevent all infections antibodies are going to be uh more dominant and that's this slide so if when we talk about protection and immunity we're talking about protection against any detectable infection that's probably antibodies are playing the major role and t cells are playing a minor role for the vaccines and i think that the correlative immunity study of the moderna is consistent with that but if you're talking about predicting against hospitalizations and death or even you know a lot of symptomatic disease which is occurring at day seven or later it it's it's much more likely that it's a mixture and that the disease is slow enough that that's seven days is enough time for for cd4s or cd8s or memory b cells to contribute so if you are in a situation where your antibodies have waned or it's a variant that your antibodies don't bind to very well or you never made much of an antibody response at all for example because you're immunocompromised in some particular way i think there's there's plenty of data supporting that these other components of the immune system can still do a lot that protect you against these more these more serious outcomes um there you go rich that's the two slide summary of uh my perspective on it and and and vaccination is gonna help out in both respects okay and that you've got an antibody response uh that's gonna uh help uh on the front lines with the initial infection but you've also got a t cell response that so you got a head start on the on the lung pathology uh so that it uh that t cell response in addition to the others can help uh impact on the severity okay yeah so like the the new york state data and the the big kaiser um preprint that came out that said look out at something like four to six months post-vaccination we're seeing waning immunity in terms of cases um right maybe going from 90 to something like 50 but still really great protection against hospitalization right like no change in hospitalizations people go well wait why aren't those connected why aren't you seeing the same numbers and it's because they're they're really temporarily two different kinds of outcomes you can still get infected you know for a few days but still have plenty of immunity that's going to prevent the lung infection pneumonia and outcomes because of the different parts of the immune system that that contribute yeah so when i tell that to people they some of them will then say why is it at in israel you got so many hospitalizations which seems to be different from the experience elsewhere as you say the vaccines are still in the 90 percentiles but in israel it seemed not to be the case and i can't explain it yeah i can't particularly explain it either i mean the vaccines even in the israeli experience the vaccines have still held up very well with hospitalization but they have seen a measurable decline in protection against hospitalizations um and yeah i uh they you know they still don't have a full-blown pre-printer paper on that yeah could dig into whether there are confounders in the math but no i uh i can't explain i mean that are available like the like the kaiser one right where they did yeah certainly the vaccines are holding up really well for hospitalizations and deaths even in studies when where there's some measurable decline in protection against detectable infections i i want to i want to wait for the peer-reviewed data on that one because you know we uh we had a communication from a listener at one point who's a statistics guy runs a website who looked at the i believe it's the same israeli data and he said you know it depends on how you break it out okay and if you if you if you uh uh tinker with the demographics and that kind of stuff you get a different set of numbers okay so yeah so i think that's going to be important and so rich just uh so yeah to expand on my answer the other way i've answered it has actually been um look i'm not an epidemiologist and epidemiology is a science for a reason you know you don't just take a plus b and you get c and what i do know is that there were a variety of different numbers and things people were saying about how good the original vaccines were you know in that population and then it took several months for epidemiologists to go through and actually figure out the confounding variables between age and geography and some other behaviors there which they talk through in this new england journal medicine paper right on the real world efficacy of the pfizer vaccine in israel and it was actually pretty complicated for them to match people up in that particular population and so yeah i've leaned more on there's a nice preprint out of england there's two nice pre-prints out of england where they've done a lot of controlling from for confounders and then again that the kaiser study looks uh looks pretty robust as well where there is evidence of of some waning and protection against detectable infections but but not the hospitalizations and deaths which yeah i think that's where we are okay um so let's round out the discussion what if you get vaccinated and then you get some kind of an infection what does everyone wants to know does my immunity look like infection vaccinated or is it different do we even know we don't and i yeah i get that question a lot right now um uh we're certainly interested in studying we're certainly studying it um other people are studying it it'll take a little bit of time i think what you probably i don't have a clear prediction for it because in that scenario you're vaccinated so you already have a substantial amount of immunity and so when you get infected um i'm sure there'll be some boost but i don't know how much of a boost because the vaccine is going to going to blunt it and so it's it's it's a little harder to predict that outcome i do expect that you will end up with some more localized immunity in your nose and mouth as a result because when you got vaccinated you got vaccinated systemically and so your immune system doesn't particularly know where to go and then if you then get infected now your immune system you're just gonna say oh that's where the virus shows up all right well let's you know let's hang out more there we'll leave at least a little bit of memory in in the nose and mouth and so i i do think that'll be interesting to to follow up on but i haven't seen any publications on it yet so a difference between infection a significant difference between infection and vaccination is that when you get infected you're seeing the uh whole the full spectrum of virus gene products okay and as you've quite elegantly shown that includes a huge variety in t-cell epitopes and there's also a larger variety than in vaccination of b-cell epitopes as well and when you vaccinate you're getting only spike okay so uh i have in i have a hard time um uh thinking about the effect of a vaccination over an infection in this regard okay if if vaccinating an infected person has such a profound effect on their immunity in particular with respect to um uh variants uh it when you vaccinate somebody who's already infected all those other non-s epitopes are they not being affected yep they just said that they just sit there it's a nice control experiment you see those are stable and then the spike ones all jump and you're like all right okay so the effect of the vaccination really is is in is just boosting the spike response okay and so uh for this virus it works out pretty well first of all spike is essentially the target of all the neutralizing antibodies and so you know having having only that that that works out well and then on the t cell side while there are 25 different proteins and gene products in storage cov2 and almost all of them are targets of t cells in different people um spike is a very large protein and it's quite well expressed only by the virus so what we observed initially was that spike's actually one of the immunodominant targets of the t cells it's most of the t-cell responses end up being against spike in an m overall just numerically the total number of t cells right and uh and many of the epitopes and so spike is big enough so that even if you are just immunizing with that one protein there are actually a lot of different t cell epitopes in it so you get you still get it decent you still get a solid breath whereas it's actually a somewhat different equation if you've got a virus with a rather small receptor protein you know and then you really may be lacking epitopes and you may have to go look elsewhere you know for decent t-cell epitopes that's not uh it's not a problem when you have this giant spike is that so thinking again about the the difference uh in the spectrum of the difference between infection and vaccination in the spectrum of epitopes uh where we're saying here is that infection and vaccination is better than vaccination and vaccination so far right it seems like like if you get infected and then get a vaccine as a boost that's better than getting a vaccine and then another same vaccine again well rich do you mean better when you say better do you mean something like quality or do you mean something like quantity or breadth yeah i don't know uh yeah all of the above yeah all of the about where what i'm immunological measurements yeah it's been yes and yes and yes actually because actually in this uh there have been two studies there's a kentucky study and then this nice uk powell study did find that people people who had this hybrid immunity if they'd previously been infected and then they got vaccinated those people had the best protection um and then the immunological measurements have been that yeah those people have the the most the most t cells the most antibodies the broadest against variants so so i'm uh what i'm thinking then is that the the uh kind of extra epitopes provided by the infection to start with not that i'm recommending this okay uh contribute to this better response if you've got more epitopes or is there something else about infection altogether that we're not even talking about that affects the response so far it could all be explained by really that that breadth and quality of the memory b sounds that just that you end up with literally a hundred times higher neutralizing antibodies against variants um with that particular combo and that seems to happen because after the infection you you generate eye quality t-cell response that then helps the b-cell response and then that product of that ends up being these memory b cells that can recognize a bunch of different variants and then as soon as you get that vaccine it it recalls those memory b cells to actually make all those really cool antibodies that you actually had sitting as sort of a library i end up talking about memory b cells as um you know they've got two kinds of values so one is you've got a certain amount of circulating antibody right and so if you get infected and the virus gets past that antibody well what's your backup plan so the memory b cells are the cells that can make more of those same antibodies right so um they're sitting there like they're like antibody factories with the lights turned off right they got the power off and then they just sit there and wave and if you get an infection right that factory turns on you crank out more insane um but they have this whole other value half the value is sort of is that making more of the same but the other half is they really are this library of immunological variants that the memory b cells are they all have different individual mutations in them that are guesses your immune system's making about what viral variants might look like because a lot of the value of memory b cells is yeah you made all this antibody and if the virus gets past that antibody well maybe that's because the antibody wasn't as good as you thought it was going to be right and maybe it wasn't as good because the virus has changed right and your immune system's had millions of years to figure out that yeah hey viral variants are a real thing right and so making these guesses and having this library this collection of memory b cells makes it so when you do have a new exposure you have all these guesses already in place of what might actually work really well and so with the with the vaccine you know uh all of a sudden those get recalled and you end up with these really potent high quality antibiotic responses so it looks like most of it can be explained by that but these other t-cell epidotes against other sites could absolutely contribute so so i have a question about quality of responses um particularly the memory b-cell responses um if you compare the vaccination response or the infection response or the combo in whichever direction you want to take that combo one thing that i start to wonder about are the data that i saw from that paper from shivpoli's lab about terminal centers and domino center changes in severe covet infection and whether those kind of changes after infection might impact quality does vaccination actually prevent you from having that severe infection so you don't have that germinal center decline do you actually get a difference in quality with vaccination infection um as would be implied by that um so how do you think that actually plays out with your memory b cells so for one uh yes vaccination is going to prevent those severe outcomes and so you know just intrinsically put you in a much better place overall really a lot of the best memory cell data well there's several labs that have contributed but a lot of the data from michelle newson's wife's lab was was really good where they they tracked both hospitalized and non-hospitalized right and they they sequenced the memory b cells and they made those antibodies and asked what what's the quality of those antibodies right and when when you waited out uh six months instead of one month you know how did it look and just overall yeah the quality of those memory b cells was really good from all the infected people so that was certainly a general question people had was well after an infection with this virus do you generate quality immune memory and that was direct data for the for the memory b cells that yes the the antibodies these memory b cells make um can have really good quality after infection the immune response is making quite good germinal center responses to that and then following up on that became essentially the hybrid immunity studies of saying well when those people got vaccinated they made these fantastic antibody responses to variants oh yep that's because we've got these studies from nuisance white and others that these memory b cells this is the evidence that those memory b cells really did get recalled when when you saw a new exposure i.e the vaccine and made some really fantastic antibodies i'm kind of thinking about your analogy of the b cell memory b cells being a factory that the lights come on but maybe also in the meantime other assembly lines have been put in place that that can then give you that variety you know additional um optimized antibody does that kind of work for you see what i'm saying yeah i mean the idea is each factor is making a slightly different version you know a version of what i'm not i hadn't been thinking through it that way i guess different versions of missiles you know sometimes a heat-seeking missile is the way you want to go and sometimes some other missile is the other yeah you could you could do the analogy a variety of ways tires tires that work on one terrain versus another right okay so let's talk a little bit about boosters um looks like the us is barreling towards boosters and you've i know what you've said about it and there's people have different views so tell us your thoughts what are you thinking and why [Music] yeah i think um so i think the simplest position to be saying no boosters really comes from looking at the available data and saying look we don't see a problem with hospitalizations or deaths the vaccines are doing what they're really supposed to do we're okay and then i think arguments for boosters come from several different lines of thought and one is well you know if efficacy against cases per se drops from 90 to 50 at six months maybe that pretends a drop against hospitalization efficacy in the future by by a few months right so so a better safe than sorry approach maybe you know get a booster now and reset that clock so that you you don't run into that trouble and so a better safe than sorry approach is reasonable to consider in uncertainties um another is to say well if you're just telling me that there's a flu vaccine right and i was 95 protected and now i'm 50 protected yeah i would like to get back up to that 95 you know i don't i don't want flu-like uh disease so those are those are a couple of them um and then when people talk about uh cases and we just say well look you know cases it's not that big a deal right like somebody in my lab got sick and they were sick for a week with an upper respiratory tract infection it wasn't coveted so we're like uh you know no big deal but you know it's and my son got sick for like two weeks right it was on there it wasn't covered but it you know knocked him out so we're like yeah we gotta just get back to getting used to this real world scenario right if we get sick with things but with kobe currently it's more complicated than that particularly for hospitals and healthcare workers you know i talk with my colleagues at the hospital and they're like look if if you test positive for a case you you've got to be out of work for a week right and so the hospitals are having trouble staffing so if if their protective efficacies drop to 50 say and they've got people showing up positive now they run into staffing problems plus staff not wanting to come in right and that scenario seems to be a problem as well so those are a couple of the factors playing into it um uh people have some concern about long coved like could you still get long coveted uh to me overall the data look like vaccinations should should largely prevent long covert i think mostly long covet looks to be a product of of severe disease either because of just the total amount of viral load or disease getting so severe you trigger unusual immunological outcomes but you know it's an uncertainty so people keeping that in mind in that in that realm is is reasonable um uh yeah and so oh right and so then lastly um there are a lot of vaccines there are three dose vaccines and they are three dose vaccines because immune memory just isn't that good after after two shots you know that after two shots of tetanus or two shots of hepatitis b vaccine you make you make antibodies and then they just fade after a few months but then you get that third shot out at six months and now you've got antibodies for 10 plus years right 30 years for the tetanus vaccine and some of that comes down to your immune system's doing a cost-benefit analysis you know simple as that you know it sees some it's it takes a lot of calories it takes a lot of resources to make antibodies for a decade that's a lot of energy and so if you see something once and it wasn't life-threatening you know it's it's worth some resources but not a lot you see something twice it's worth some more and if if you get infected with something a third time right it really usually forces your immune system to go okay that plan was not working right we need to commit some more frontline troops to this you know and so that that's there's a cost-benefit analysis that the immune system is doing and so three doses of a vaccine tends to generate longer lasting memory than just two doses and so the prediction would be you would sustain antibody titers for a longer period of time after that after that third dose uh the reasons uh not to do it not to get a booster would be one or not to approve booster that'd say one would be reactogenicity concerns right just basic safety issues so the booster clinical trials look fantastic in terms of their immune response the the antibodies are broader against variants they're they're boosted back up to probably two to four times the level of what the second vaccination gave um but it was only about 100 people right so that's not a lot of reactogenicity data so it was safe in those hundred people my understanding is there's now they did studies in israel of a couple thousand people and the reactorgenicity was basically the same as it was to the second dose so that would match expectations and certainly from a safety perspective that would then be would be fine and so then the other concern is really the global equity concern that look you know how can you give a third dose to people when they're all these people who have gotten a first dose and and i think there are a number of reasonable perspectives on that i'll say i certainly care about global equity right i mean pre-covet i spent my entire decade working every day on an hiv vaccine [Music] but you know practically speaking in terms of covet vaccines in the united states the u.s has to retain enough vaccine doses to vaccinate all the unvaccinated people in the country which is you know probably close to 100 million people still um you have to still try to vaccinate those people right and so you have to keep enough doses around to try and vaccinate those people and hopefully you convince them but it hasn't really been happening right so and i think if you have to keep those doses around why not give them the people who actually want them instead of having them expire and right now we've got millions of doses expiring on a regular basis because they're being held around i see no downside to allowing people get those as a booster if people aren't getting them as an unvaccinated person to be clear a dose of vaccine into an unvaccinated person is absolutely more valuable than a dose into a vaccinated person by any metric i mean deaths hospitalization transmission you know you name it but if you can't give it to that person yeah using it as a booster i i don't see it as a loss i really liked what carlos del rio said about it on the ucsf grand rounds we did you know he's a public health expert at emory he said look it's like when i was a kid and my parents told me to finish my dinner because they were starving kids in india and said yeah you know it's important to care about disturbing kids in india but the dinner on my plate doesn't help those kids at all you know it's a false dichotomy you can't getting getting vaccine to other parts of the world is very very important and but it's a false dichotomy it's not an either or it's really an and that's that's my that's my take on it uh so um one of the um [Music] one of the things people are thinking about is that and you touched on this briefly let's just just make it clear infection vaccination incredible breath of antibody response are you saying after a third shot you get this a similar antibody breath yes so both so in the the moderna trial was the modern booster trial was first and now when they compared their original vaccine as a booster and then they also compared a beta as a booster and in both cases they generated good neutralizing antibody breath against variants and boosting boosting with the original was just about as good as boosting with the beta even for getting neutralizing analyze against beta so yeah a similar type of thing as hybrid immunity that that this is a virus that each time your immune system sees it even if it's seeing the same virus and not actually seeing a variant it is learning to recognize variants better ah so you don't really need to boost with variant vaccines right right so that's the other thing that certainly people like wait if we're gonna do a boost why isn't it a delta boost and that's a that's a fair question and one reason is that you have to wait right and the other reason is really the moderna trial was was directly asking that question and i was i was definitely a proponent of that trial occurring and comparing those things like yeah now's the time to learn you know do you need a variant booster or is is uh original strength or vanilla or whatever you want to call it you know going to get the job done and yes it's going to get the job done and the pfizer trial um corroborated that that evidence so based on everything that has happened with thinking about immune responses to cyrus cov2 and vaccination and infection and all of these things what do you think we as immunologists have actually learned about the immune system that's a huge amount honestly because a lot of human immunology is restricted by the fact that in any single place and time you've only got a few cases of a certain infection or a certain disease with a certain complication or even a certain vaccination you know and so you have all these studies that were five ten you know 20 people that you were or even two people that you were trying to extrapolate from and now between the vaccination programs and the infections you know you have these studies that have that are very well powered essentially to answer good questions so honestly [Music] it's hard for me to think of anything else that we've learned as much about human immunology as we have had with covet in part because there have been really good you know well-funded nih supported groups that that had all these pipelines in place you know to measure the right things in the right ways and so that the tools were there and the other is you know what i was just describing actually having samples available for comparison within reasonable windows of time has allowed for really quite statistically robust conclusions about how the immune human immune system really functions people still ask now the time to predict immune memory you know like what's memory going to be like you know four years from now like we don't know you know why because it hasn't happened yet so we we talk a lot of what we talk about your work and others is mainly with mrna vaccines but some of the generalizations we've made today can they be applied to say adenovectored spikes or even inactivated uh vaccines that are made elsewhere or subunit vaccines yeah they can definitely be applied to to most of those yeah i've certainly been impressed by the clinical trials that i've seen studying uh adenoviral um basically all astrazeneca and then an rna vaccine has the second immunization so first immunization estrogenic a second immunization rna vaccine and a couple of those have actually compared have had the full comparison you either get two shots of adenovirus or two shots of rna or one shot of each and the mix and match uh did in fact look significantly better and uh so there's some of those things that we were learning about as well it's just there have been so many more people vaccinated in the us with the rna vaccines than j there's just a lot more limited data we i mean here at lgi we're definitely studying the jnj vaccine and we've just been trying hard to collect enough people at the right time point so that we could make a meaningful comparison great shane karate as always very illuminating really appreciate you joining us thank you so much yeah i really enjoy this i always feel educated immune [Laughter] when uh when we're done you know the immune system is uh really cool uh it's you know thought of everything seems like yeah yeah uh i mean the immune system is really good at recognizing and dealing with this virus and definitely all of these approved vaccines are really good at dealing [Music] definitely our biggest challenges in this country have been that we've just had so many people unvaccinated and you know if we had 90 of people vaccinated you know we would really not be having any problem at all now and it just hasn't uh just hasn't worked out that way which has been really sad but like in san diego you know the numbers that we showed was it was like last month there were 520 hospitalizations of unvaccinated people and they're like 13 of vaccinated people i mean you know it's just man you want to talk about a single number that shows you how good vaccines are those are the types of numbers they yeah probably the vaccinated people went home too yeah oh yeah yeah vaccinated people they all went home yeah absolutely all right well yeah thank you shane yeah thanks take care bye-bye thank you always great yep clarity yeah and i'm just so impressed like i said with the immune system just thought of everything it's pretty fantastic it's amazing it's fantastic if it works it doesn't always work that's true i mean sometimes you know it does a little too much or not and then i can't go outside some people don't have it you know yeah sometimes it causes disease that it shouldn't be it's cool but i think viruses are cool too i gotta fight back for viruses nobody wants to because they kill you but they're really cool i kind of sort of wanted to ask him the ultimate hypothetical question maybe we'll get him another time which is 10 years from now are we going to be vaccinating people against sars cody too yeah i i think that's very interesting and just to think about what do you think rich i know i know what i think what do you think let's pro let's poll us do you think we're going to be vaccinating in 10 years yes or no yes or no yes or no yes brienne yes kathy yes vincent no now can i qualify my answer i don't think we're gonna need to but i think we will okay that's fine i i think that we might need to because i'm not sure what the percentages are going to be like uh for those who are immune i mean maybe not 10 years but in 20 or 30 or 40 maybe the only reason is because of what ralph barrack said back in february he said you know the common cold coroners probably did the same thing when they emerged from some animal reservoir where we didn't know anything about pandemics thousands of years ago and eventually they became benign-ish and maybe that's because of large levels of population immunity right can you name anything that we've ever had a vaccine for where we now no longer vaccinate because we're eradicating it yeah but you have to have a single reservoir but but the history of immunization is too short to be a because these viruses have probably evolved over hundreds of thousands of years to become what they are now maybe it's not even a viral change also well and i think the other question is you know shane mentioned this that some of these situations where you're getting additional immune experience are giving you such breath that you can neutralize as far as kobe 1 in addition to tsar's cov2 what if we were to figure out a way to get breath against more coronaviruses that might keep us vaccinating and preventing other diseases as well i mean i think it's a fair point that yeah we haven't seen that happen i always use that in many levels to say oh i've never seen a virus become more right but i agree with that but you know i think we have a lot to learn from the common cold coronaviruses especially you know we learned in the past year that they do antigenic variation which none of us thought they did and how does that impact um what happens in people we really don't understand so i yeah i agree it could go either way but so many missed opportunities to have studied them in the past really it's in it's true because and if you talk to the corona community you know and the emergence of sars1 they all became sought after and they they said you know up until now nobody cared they infect the animals and they cause colds in people anyway that's very interesting good stuff and um i i think um immunology granted to address your question is learning much more than virology is right now because you got to work on this bloody virus in a bsl3 yeah and that's hard for the immunologist give me some serum and and i'll do a lot we're a fine needle shane's uh shane's uh approach to that was really interesting and that we've never had an opportunity to look at this large population in this kind of detail i think flu has had right a lot of people get flu every year and so there's a lot of flu immunology but there's nothing like a i don't know what during a flu pandemic last one was 2009. i don't remember so many immunological studies do any of you i i don't really either and i don't remember as many kind of immunological insights or situations where you would now want to make sure that you show these data in a class or in a textbook because it's such a kind of perfect example of whatever phenomenon whereas here i want to put so much of the data we've been seeing right into my class plus that pandemic was one wave right essentially yeah it was it was one way and remember from friday's excess mortality uh very low mortality i think 400 000 people died um which is not zero it's still but it's yeah it's not a lot when he was talking about the size of spike i was trying to think how big is ha in this is it much smaller and is that why there's a crappy t-cell response to uh maybe flu vaccines or something like that does anyone know what the size of the ha is roughly i don't i only know the size of spike 1273 amino acids uh what is the length of influenza ha in amino acids let's see what do they do without google i don't know in textbooks we went to the library i actually loved going to the lowest levels of the library nobody was there it was all dusty and you opened you opened an old volume from the 50s and you see what people would do i just love that that was cool wasn't it well i'm not finding it um quickly while you're looking i was going to make another comment about um influenza pandemics versus this one yeah this is a completely new virus yeah and you know as time went on the different manifestations of the viral infection you know as the immune system you know as he was talking about you know as you go three weeks out and the disease gets more serious and now it's in your lungs and then you know all the things with the various types of long covet and so forth i mean i think that lends itself to a lot of people wanting to know what's going on and to my knowledge you know influenza doesn't have that breadth of organ systems and the you know the blood clotting and all just all those different kinds of things that that we have with stars cov2 infections i think the avians do but there's so few cases right yeah it's very different that could vary i'm not finding the bloody length and people are sitting there screaming at me i have 566 residues okay maybe roughly half the size of spike huh yeah i mean although i think that that's a that's the monomer not the timer but i think 566 is what i'm getting okay i don't know if it explains anything but anyway let's do a couple of emails here um brienne can you uh take that first one sure uh brea or brie right hello twiv and thank you for all you do flagstaff arizona partly cloudy and 60 fahrenheit questions for the covid clinical updates if you are fully vaccinated and exposed to covid does it give your immune system a boost because it's reacting to the virus same question but if you were to have a breakthrough infection i am of course not saying that one should intentionally expose themselves but i'm wondering if the vaccine provides protection from severe illness but community spread is still increasing would a happenstance exposure potentially help boost immunity for a little bit sorry if the question is not clear thank you for your time best of wishes brea bree something like that um and i would say that we just talked a whole bunch about that in theory um if you are infected again you would get a bit of a boost yes yeah we did discuss that with with shane so i think a la brea tar pits right that's what i was thinking too but who knows who knows how people say it so let me let's i i was looking on the cdc website this morning and i'm not sure if that's a good or a bad thing frankly but sometimes it's good sometimes but i do look at it and they do not say there's evidence for transmission from vaccinated people who get infected okay they say there is not evidence for it or do they not discuss it at all no they say there's no evidence for trans for transmission from infected vaccinated people i mean i think that's been implied in a lot of the discourse but uh i'm not sure there's good evidence for it i wondered if any of you had seen anything i mean [Music] because there's too many penguins on the iceberg too many penguins okay but this reader listener's just saying about transmission after vaccination yeah and i cannot cite okay a publication that demonstrates uh a uh vaccinated person being infected and transmitting the infection okay but that doesn't mean it doesn't exist just means that i've got too many penguins on the iceberg so well no i'm she's not asking about transmission she's just asking sure is it going to help you as an individual she says does a vaccine provide protection from severe illness but community spread is still increasing that my my understanding is that she's saying the inc the spread is still increasing even if you're vaccinated no i i read that as is she helping she thinking that if you're vaccinated but there's a lot of virus in your community are you going to be is that going to be a good thing for you to potentially get exposed got it all right all right so i should have given you the next one brienne i'm sorry because that's okay this is for you um rich you want to take the next one please sure judy writes hi twivers this one's for brienne so you're listening brian i am i'm listening she and i have have a have shared an interest in the germinal center story of sarge kov2 infection so i thought she'd appreciate this paper as you know there was a paper that came out back in august 2020 by kaneko at l that showed that people infected with sarge kov2 did not develop germinal centers oh that was yeah that was a big that was an immune episode right yeah i believe so is that an immune okay i think it was a meme uh i think it was covered on twitter at the time whatever yeah and she gives a link to the paper well it is now almost exactly one year later and another paper has just come out showing that persistent germinal centers do form in people vaccinated with the pfizer vaccine which gives a link to that to nature paper just more evidence that immunity from vaccination is not the same and indeed is probably even better than immunity from natural infection i love the show so appreciative of all the things you do for our community stay well keep on racking yelling judy okay so i'll leave it to this is for brienne you got a comment so i think that um it's a really interesting observation but if you look at that original paper with the terminal centers those were in patients who died they did [Music] the they got germinal centers from patients at autopsy and shane mentioned some studies in non-human primates and he also mentioned somebody else doing them in humans where they were taking the lymph nodes um in live individuals and it seems like they were seeing some um some good germinal centers in those cases and that's kind of why i asked shane about this because you could imagine that maybe you know that was only something that destruction of the journal center was only something you see in a really severe case so it's sort of hard to have that comparison um i've been really intrigued by what was going on there and how that can change the quality of the response but i don't think that that always happens during infection um and i think we need to look more at some of the studies that shane mentioned about looking at germinal centers in living animals or patients so it's not just the severe individuals i'm sitting here thinking that uh throughout this episode we've been talking about germinal centers and there may be a fraction of our listeners out there who are new enough so that that goes right over their heads could you in 25 words or less brienne tell us 25 words or less i'm going to start i'll give you 50. terminal centers are areas in a lymph node or in the spleen where a b cell goes after it sees its antigen in order to further develop it can get better antibody production abilities um so it can change its specificity um it can sort of change in terms of breath and it can become a memory cell and it can also learn to do some new and better functions and so germinal centers are kind of the place where uh b cells mature um further after they've seen antigen when they're in the lymph node higher education for b cells i was thinking where b cells go to party but you kind of threw water on that where b sales go to get mature it's not partying i usually say that secondary lymphoid organs are where the immunology party happens so good now judy said more evidence that immunity from vaccination is not the same and indeed i would agree it's not the same as infection but probably better than immunity from natural infection i'm not sure that shane would say that right yeah that that's kind of that's specifically why i was asking him about the quality yeah um and i think that you know he did not support the idea that it's necessarily better okay for those who want to know more twiv 161 concerto in b where we had gabrielle uh victora on and it was all about terminal centers and that's where i learned what a journal center was that's just extraordinary it's natural selection for b cells you know kathy i don't know if you're on twit the qual when brienne says quality i just think of this old meme we had on twitter years ago where someone wrote in the koala tea from something and it turns out it's a play on merchant of venice the quality of mercy is not strange the tea and the guy wrote it to us as a joke the koala tea in its koala is in the koala animals koala tea oh what was it i can't even remember the original twif let's see quality twiv how about that the quality of marseille no anyway you were not on twit but that's what i just wanted to tell you because it's from shakespeare and the guy wrote it to us in a cryptic fashion and we're like what is this what is this koala tea and someone wrote in and said you idiots it's from shakespeare here's 1281 the one we uh uh picked on last time virus see the world the little uh the descriptor for that uh has the koala tea of marseille so maybe embedded in there somewhere that was you and me it was it was just a funny episode before we really got popular and there were just a few people listening and because nowadays we have maybe now people are going to weigh in on this because they know about it i thought you would appreciate that kathy being from a uh a line in shakespeare yeah yeah no and i remember having having heard that yeah it was before i was on the show yeah 81 was before bk right yeah it was even before it was even before the first one that i went to or heard which was the one at montana state that was 92. the first one you were on was when we visited um michigan right yep yeah that was in 2011. i remembered you were driving me somewhere and i said what are you going to do are you going to shut your lab down so this was 10 years ago probably right and you said i don't know i'll just keep listening to twiv and i said well why don't you just join it and i don't remember that and you said i'll think about it that's what most people say yeah yeah all right um kathy can you take the next one dan writes greetings from greetings twiv team and hello from des moines high today of 33 c tropically humid and still a bit smoky here not great weather for hanging from a rope cleaning windows but someone has to do it i suppose wow we're about to have a giant state fair here and after the not so great study on coveting deer i'm wondering about the potential for zoonotic spread just to set the scene the iowa state fair normally gets over a million visitors very few people here are wearing masks daily cases are trending up going from 50 or so per day a month ago to over 1500 yesterday so wow that's a huge increase population here is around 3.3 million with about 50 fully vaccinated at the state fair there are large display barns filled with sheep goats cows pigs and chickens as well as other random animals for example they have a really big elk the barns generally have pretty good air circulation large doors that are kept open big fans etc but they are covered and will be filled with people what's the word on transmission to and from farm animals to me a guy that cleans windows it seems like this might present a dangerous opportunity for a zoonotic crossover event what does twiv think regards dan so uh you know i think if we were going to have had spillover to farm animals by now we we would have heard a lot more about it you know we have heard about some spillover to mink and cats and great apes and zoos and and things like that but we haven't heard too much about farm animals so i'm guessing that it's maybe not going to be an issue what do you guys think i think that uh with respect to sarsko v2 the biggest danger here is the people uh first of all you know all these people with only half vaccinated in this small space uh sounds like a super spreader event to me and i would say that with respect to uh zoonotic infection from either a sars virus or any other virus for that matter we've been doing state fairs for as long as humans have been around and you know the risk is low to to negligible uh what i think is even more interesting is spill back whether uh some of these uh creatures are to pick up sarsko v2 from the humans okay and whether that could uh seed some sort of event i doubt it's seeding an event but i wouldn't be at all surprised if a couple of creatures now what do we have here for creatures sheep goats cows pigs and chickens no tigers all right tigers and gorillas you know they're not cheetahs or lions yeah have been no reported cases of pigs horses sheep chickens or cows getting coveted but they haven't been this is from last august and it says it's actually from the college of uh food agriculture environmental sciences at ohio state and they said but nobody has checked them in the lab to see if they're susceptible i must have been done by then since then i haven't heard it for sure i i also think dan thank you so much for writing a good point and thank you so much for listening thank you for watching the windows yeah great can you do mine yes uh for for uh for any kind of person um these are great questions and great logic um so don't sell yourself short here dan i think it's um if i were going to this thing well first of all you know i always see pictures of little kids kissing pigs at these fairs you know and i think that's not a good idea um if i were going with a lot of people i'd be wearing a mask yeah oh i'm not going to this event right i'm not going to go at all if i were somehow forced to go and i can't imagine how that would happen if someone offered me a million million dollars to go i would go and i would wear a mask and i would put the million into microwave.tv just so you know folks okay i'm not going to keep it for myself i was just thinking about the reason why they have the doors open and the fans are probably because of the smell yeah you bet but i think in the next year we're going to learn about a lot more animals yeah including wild ones i'm looking forward to hearing about that all right let's do one more here from charles hello twivers another summer's day in north carolina and 93 f 34 c a bit humid some clouds that may land rain later today this may bug me more than it should but i'm sick and tired of articles and papers condemning antigen tests for stars cov2 because the authors are following the fda's lead and using the wrong quote gold standard end quote pcr should not be the gold standard viral culture should be see link one for from the nih and he provides an article antigen-based testing but not real-time pcr reaction correlates with uh sars cov2 viral culture yes from january 2021. interesting the energy test just demonstrated a higher positive predictive value 90 than pcr when compared to culture positive results not surprised actually i'm not surprised either i'm not either that's really good yeah let's put that in the queue the latest example is from germany entitled quote diagnostic efficacy of rapid antigen testing for stars cov2 the covid19 antigen kovac study that's link two it's met archive i found it at medpage today with the headline roche abbott covet antigen chest just so so in world world data unsatisfactory for screening asymptomatic people say german lab professionals link number three that's from medpage uh so the med archive uh conclusion is the sensitivities are unsatisfactory this calls into question whether their widespread use is effective you know that's funny because thursday daniel reported on an evaluation of at-home antigen tests and they that was fine well does the met archive say that it's unsatisfactory or does it matter commit archive says it's unsatisfactory that's the conclusion okay so then continuing with charles what the hell do you want a screening test of an asymptomatic people to do i would think you would want it to show if that person is infectious or not which test is better for that well in most circumstances it's the antigen test if you're tested very soon after exposure the pcr test would be better but only for a day at most if you're asymptomatic and non-infectious would you want a test to show you are infected not me sorry for the rant i have been an advocate for antigen testing for a long time going back to before twiv 640 with michael minute in july 2020 with a letter to twitter in early june of 2020. it upsets me that an uneducated i.t guy gets it and those doing the research don't okay it really pisses me off i can't imagine how you guys feel when you see so much bad research thank you for letting me rant charles i think you got infected by the twiv brand thing right [Laughter] yeah this is uh this happens a lot charles especially in a pandemic for i keep thinking i keep thinking about my daughter's experience in london where you know you just uh as a matter of fact i was gonna you maybe i'll use this as a pick down the road you know you can go to the national health service website and say send me rapid antigen test boom they come to you yeah you can have one you can you can do you know the the closest equivalent that i know of to lick a stick you know you can test yourself every day for free so i remember uh when um the the the cdc provincetown study came out a few weeks ago remember vaccinated versus unvaccinated persons in this outbreak the pcr uh viral rna copy number was equivalent in both right and they got they got all worried based on that but then as as brienne pointed out on that episode the singapore study shows that viral rna levels declined very rapidly in vaccinated people compared to unvaccinated people at the same time there was a paper a separate study where they looked at vaccinated and unvaccinated people had become infected and that's determined by pcr positivity over 50 percent of the in vaccinated pcr-positive people had no antigen positivity by one of these antigen tests which to me suggested that little they have little bits of rna in them that are not infectious and not even making proteins probably so i i think the antigen tests are as that first paper shows they're very good indicators of infectivity so there you go charles good job and you're just real you're just you know we're all just something charles is just but you're not an uneducated uh charles that's not correct to say that you're educated in your field and perhaps more outside of that who knows again great logic it's good logic yep okay let's do some uh picks here brienne what do you have today for us i suppose i must be on some sort of a little arc or something yeah so this is called how the cat gets its stripes it's genetics not a folk tale um and this actually goes into um showing details uh of a or this is a new york times article that talks about a paper um where they were able to look at a gene um that is responsible for uh the tabby stripe pattern and are actually able to even see that pattern in embryos before uh the cat or the cat embryo has hair follicles um and so this reports on the research on that um there are some quotes here from uh hopi hookstra who does similar things in mice who i think has been on uh twivo um and it's just really cool and gets into you know uh the genetics of how exactly this happens it looks like my cat there also it looks like my cat and rich's cat uh so uh is this a segmentation thing um it doesn't seem to be segmentation in the way that at least i learned segmentation okay um but i guess we have to ask somebody about sort of more specifics about how they mean segmentation i think it's really just how this pattern forms but it has that similar kind of gradient aspect to it that the segmentation stuff does so you uh well i got familiar with all kinds of cat genetics when i had a postdoc in my lab who is an international cat show judge and is very much aware of all the genetics of cats and and then just for instance the famous story about siamese cats having a temperature sensitive coat color phenotype you know so that at the tips of their ears tails and paws uh it's where they express the pigment and so that's called pointed um but um that's and it's a tyrosine tyrosinase missense mutation i'm pretty sure that causes that so there's yeah this is a continuing story on that line it's really cool so when hopi was on tuivo she talked about her paper where they had these 13 striped squirrels right and her postdoc said i want to slice the skin into thin strips and do transcriptomics on each slice to find the genes that make it colored and not colored and she said no way there's just no way that's going to work there's a nature paper right they found the gene that that controlled the striping but she let him do it it's good right that's you may not think it will work but go ahead as someone would say sink yourself but he didn't it worked that's cool cathy what do you have for us uh so i have two things one is a cool video um i think it looks like i misspelled it here it's kurtz kazakht on gyruses and uh it's a youtube video about giant viruses that's really well put together um i'm afraid to click on it because i don't want it to start but um with sound try it let me see if it actually starts because i don't hear it just i went there but i watched it i didn't is a web page um that is uh in a nutshell is what kurtz act kind of means in german and i did misspell it but i'll fix it um and so the title is this virus shouldn't exist but it does and it's had over 12 million views but it's really well animated and i only watched it one time but i didn't find any flaws with any of the science in it i don't know if you did rich uh i was i was watching carefully for them to make a uh a misstep with this and talk about a fourth domain of life or something like that my only gripe about it was that uh in you know for me they made too big a deal out of uh virophage you know because to me those are just satellite viruses they're they're that big a deal yeah okay but that's okay it's uh uh it's a uh an entertaining and actually quite highly accurate and educational video it's nice well done yeah and then the second thing i picked i i just had to pick it it was uh yesterday's astronomy picture of the day and it's just beautiful so it's from september 6th and if you mouse over it um it highlights all the various things there's a satellite trail and a green air glow and where saturn is and where the milky way is and where the pine tree is which was the reason for taking the picture uh the idea was to photograph a stack to ask klein in front of a central band of the milky way and the plan worked um it's a time lapse and they captured a firefly it just makes you know makes this picture over the top so you have to check it out a lot of flashes one two three four like 20 flashes of the first like cool i thought this one was absolutely beautiful and i have to thank you kathy for getting me hooked on uh apod because within the past week or so there have been a number that have been just so gorgeous yeah yeah so i'm pretty sure kyrgyzstacht was a twiv pick so i searched kurtz twiv and i found a letter from uh peter in wiesbaden who wrote p p s vincent your pronunciation of kyrgyz was absolutely delicious so i said it right many years ago probably not anymore well there's a z in it so it i think it's kurt's gaza he was german he said it was delicious and i probably said it wrong you know sometimes when people say there's something in another language delusion in a kind of neat way it's it's cool right yeah it's like short is like said so in a nutshell said short mitch what do you have for us uh so my justification for this being a science pick is that it's research but it's journalistic research uh i just read a book finished reading a book called triangle the fire that changed america by david von draley i got on to that because he's a columnist i mean he's had a number of different gigs but he's also he writes columns opinions and etcetera for uh the washington post and i really liked columbia recently so i looked him up and i discovered this um uh book which it turns out is uh quite appropriate for labor day we had a heather cox richardson uh article the other day uh that focuses that starts with a triangle fire this was a fire that happened in 2011. in the garment district uh in uh i'm sorry 1911 in the garment district near uh washington square in new york city uh that was sort of the breaking point for um union demands and otherwise for safe working environments and et cetera that everything went wrong in this and it kicked off reform labor reform and also actually uh based on this book kicked off uh political reform that went far beyond that one of the uh major investigators in uh in the committee that investigated this fire was i'm going to blow this francis what's her last name she became the first woman cabinet member uh as secretary of labor for franklin delaware roosevelt that's a a great book and a really enormously scholarly effort i don't know how people do this research this stuff so that got me to pick to to uh i guess he he referenced this in the appendix of his book a website uh that's from cornell university called the 1911 triangle factory fire that's a web archive of everything you ever wanted to know about the triangle fire um that includes uh pictures and everything else so this is a major event and um it's a really a good uh example of how to find the truth which i really enjoyed you know i hate to say francis perkins thank you if this fire happened today certain people would play it down and say well you know the uh the you know one of the reasons that as many people 147 people died in this fire was on the eighth ninth and tenth uh floors of a uh this building the ash building i think it was called uh and uh one of the contributing factors was that uh one of the doors that might have been used as an escape on one of the floors was locked and uh there was a criminal trial following the fire that tried to uh nail the owners of the building the the people who ran the country of the company for uh having that door lock and uh they were acquitted okay because the instructions from the judge to the jury was you need to be convinced that the owners absolutely knew that that door would be locked at that time on that day yeah okay yeah but he did he locked it uh he said he locked it because uh he didn't want shirts stolen right from the factory yes well so it's gonna be locked all the time they should have convicted him so those uh those uh raunchy people were around then as well you know yeah but i'm thinking of you know massacre thingies that happen and certain people say it never happened or it's not that bad blah blah blah all this just try and politicize well it could be it could very well be that one of the reasons that this uh you know had such an effect was that it was just so blatantly obvious and people you know a lot of the deaths were people jumping out of the windows because they didn't want to burn i agree but when kids are shot into school and nothing happens with gun control right you're right you're right i don't know if it was a better time it probably wasn't right but at least something good came out of it as right as as the fire that changed america indicates i i just read this her column this morning that's why i'm thinking about this a lot okay that's cool thank you uh so my pick has to do with these two fda people who are resigning and i'm just curious about what's going on here so i have a new york times article but you can find lots of articles about this the times the two top fda vaccine regulators are set to depart during a crucial period so so dr marion gruber is director of the fda vaccine office and her deputy dr phillip krauss will retire gruber in october uh krause in november according to an email that marks the the um i guess he's the head vaccine guy at the fda peter marks sent the staff members on to tuesday and the article says one reason is that gruber and cross were upset about the administration announcement that adults should get a booster we have two listener picks debbie twiv has become a necessary part of my podcast diet i love eavesdropping on this very cool journal club you have exploded my understanding of viruses and biology in general i look forward to every episode i thank you for all your time effort wisdom humility and good humor and this pick is a website called um river runner the site allows you to follow the journal of a drop of water in the contiguous u.s to the ocean using prodigious data sets from the u.s geological survey you can adjust that's awesome the speed and detail of your journey and you can pause anywhere along the way unfortunately water that flows north through canada stops at the border that's funny i hope someone takes up the challenge to do this for the whole north american continent rabbit hole warning enjoy uh debbie is from winnipeg oh that's so cool that's awesome it's all based on the flow of water right oh you click on anything and you can see how everything flows neat gives you the local stream and then the river and and then which lake or ocean it dumps into well then it zooms in yeah and there's zooming it's cool and then it follows it wow why do why do rivers meander i was thinking about this the other day when i was flying to austin you know why are they meandered there's a reason for that right geology i mean i think it has something to do with how long the river's been there um uh eroding because you know if you look it's like you can see on this map there they loop and then they go back and then they loop right someone's going to write us and tell us okay we have another one from lynn good morning very early 12 30 a.m clouds in a dark sky here in western massachusetts a damp and damp from a day of drizzle 61 f-16c just listened to the morning medical report from kansas with you as guest you are nothing less than terrific and the program is worthy of a daily watch it was just a bit disheartening to see kansas not doing well with vaccination despite this amazing show with these articulate doctors answering excellent questions this should give you many more twiv listeners and that is cheering i thought those doctors were really good i was impressed they were both upbeat knowledgeable good senses of humor right they were really good i have a listener oh by the way in that star trek mask thingy kathy that you had sent out with the the star trek guys with the masks he had found that or sent it with don't be a red shirt wear a mask is it true that on star trek if the guys with the red shirts would get killed on the ground uh yeah uh uh predominantly yeah i think kathy you dug up some data on that yeah so i think rich put the uh figure into the slack channel and i just found the data that yes red shirts uh sixty percent of those who died or were bringing richard because of the uh role that they had on in star trek yeah and i think that it's just also just sort of a general saying at this point of you know being a red shirt is sort of being the extra one who's around who's yeah disposable so on this kansas show at the end of the episode this one doc forgot his name he said please wear a mask don't wear a rip don't be a red shirt and he put this slide up and i had no idea what he was talking and then then i saw it on you on the slack it was actually a few days before on the slack channel okay i have a listener pick an excellent article from the atlantic's katherine wu who rivals ed young in her science writings her thesis waning antibodies doesn't mean waning immunity memory b and t cells are going to kick in to fight off the virus and prevent severe disease and death seems likely that for the majority of the vaccinated population who are not immunocompromised or very elderly boosters should not be needed i'm sending the link in a separate email my phone is behaving a bit wonky best regards lynn just a retired molecular biologist it sounds familiar huh waning immunity does not mean waning memory cells exactly i heard that before i use uh paul offits fire extinguisher analogy all the time for the immune system i think that's great so uh i guess oh yeah i didn't put the link in it was in a separate but i think this is the correct link yeah uh yep all right i think we've heard from lynn before because i recognized just a retired molecular biologist that'll do it for twiv 802 microbe dot tv slash twiv for the show notes you can send questions and comments to twitter microbes and if you like what we do consider supporting us microbe.tv slash contribute kathy spindlers at the university of michigan in ann arbor thank you kathy thanks this is a lot of fun brianne barker drew university bio prof barker on twitter thank you brianne thanks it was great to be here rich condit emeritus professor university of florida gainesville currently in austin texas thank you rich enough always a good time i'm vincent dracqueniello you can find me at [Music] virology.ws i'd like to thank the american society for virology and the american society for microbiology for their support of twiv and ronald yankees for the music you've been listening to this week in virology thanks for joining us we'll be back soon another twiv is viral [Music] you

Channel: Vincent Racaniello

Views: 17,503

Rating: 4.8557992 out of 5

Keywords: virus, viruses, viral, virology, COVID-19, SARS-CoV-2, coronavirus, pandemic, vaccine, antibody, T cell, variant of concern, booster vaccine

Id: nEB4oxO9F1A

Length: 107min 35sec (6455 seconds)

Published: Wed Sep 08 2021