Dowling & Yahnke Wealth Advisors partnered with La Jolla Institute for Immunology (LJI) to provide you with an expert’s update on the COVID-19 vaccines. Dr. Erica Ollmann Saphire, a professor within LJI’s Center for Infectious Disease and Vaccine Research, was asked by the Bill and Melinda Gates Foundation to build a global consortium (CoVIC) to quickly identify the best antibodies that could be used to combat the novel coronavirus. During this webinar she provides an update on the state of the pandemic, share insights on the current COVID-19 vaccines and others in development, present recent findings from the field, and answer commonly asked questions.
The information contained in this webinar is for information and educational purposes only and represents the views and opinions of the presenter only. This information should not be construed as medical advice. Viewers should consult their own physicians before making any medical decisions. Dowling & Yahnke, LLC and La Jolla Institute of Immunology are not affiliated with one another.
The below is an audio transcript with time guides automatically captured by Zoom. Not all text may be accurate.
Anna E. Diaz
00:02:45Good to have you all here today.
00:02:48My name is Anna Diaz and I’m a Lead Advisor with Dowling & Yahnke Wealth Advisors. today I’ll be moderating today’s conversation with Dr. Erica Saphire.
00:02:58On behalf of all of my colleagues D&Y, we’re thrilled that you’re here to participate in today’s conversation. Which should be very interesting and obviously very timely.
00:03:07As a local San Diego, I’m extremely proud of the intellectual capital that lives in our city.
00:03:13It’s organizations like the La Jolla Institute and the research and the critical work they’re doing at this very important time in our human history, as you all know.
00:03:23So before I give you a little bit of background on Dr. Erica Saphire, a little bit about our Firm. D&Y was founded in 1991, which means this year is our 30th year anniversary.
00:03:35Dowling & Yahnke, was a pioneer in the wealth management industry, choosing since its founding to be a fiduciary, which means putting its clients interest first and choosing to be independent.
00:03:45Today, we manage over 5 billion in assets for clients, providing portfolio management and financial planning services to over 1,300 clients in San Diego and across the country.
00:03:57We deeply care about the financial lives of our clients, their well being, and remain humbled by the trust you have placed in us at this very important time.
00:04:08So let’s give you a little bit of background on Dr. Saphire. Dr. Saphire is a professor at the La Jolla Institute of Infectious Disease and Vaccine Research.
00:04:18She was asked by the Bill and Melinda Gates Foundation to lead a global coronavirus immunotherapy consortium to quickly identify antibodies to combat the coronavirus.
00:04:30She also lead a consortium that united academic, government, and industrial labs across five different continents to understand antibody therapeutics against various viruses like Ebola, Marburg, Lhasa, and others.
00:04:45Most recently, and very excitingly, she was awarded the Scientist of the Year, by ARCS, for her work around the coronavirus.
00:04:54So for our guests, thank you to many of you because you submitted questions before today’s presentation and it was very helpful.
00:05:00Dr. Saphire has kindly curated her comments today around a lot of those questions.
00:05:06We do encourage you, during today’s talk, to keep those questions coming. So you’ll notice at the bottom of your screen there is a Q & A button.
00:05:13Please feel free to send those questions as they surface for you and our team behind the scenes will be aggregating those, and then I will lead a Q & A session with Dr. Erica Saphire after her talk.
00:05:24So before I introduce Dr. Saphire to began her conversation, I do want to introduce Christopher Lee.
00:05:31He is the Chief Advancement Officer for the La Jolla Institute, he will give some background on the organization and then he’ll pass it over to Dr. Saphire. Thanks to all of you for being here. Chris, I’ll send it over to you.
00:05:46Thank you, Anna. Thank you all for giving us the chance to introduce the institute and Erica on such an important topic, during such an important time.
00:05:57Congratulations to Dowling & Yahnke for their 30 year anniversary. We also are an organization that’s about 30 years old in San Diego and like Dowling & Yahnke a real gem.
00:06:09What I normally would do while presenting you this in person, I would ask, “Who has heard of the institute?” To be honest with you, in the past, we wouldn’t have had a lot of hands raised.
00:06:24 But given our great work in this last year and Erica’s great work over her career, the institute is getting larger exposure for being the lead and
00:06:36Since the organization than it is in one that all San Diego can be proud of. So I’ll give you just a quick minute overview of who we are.
00:06:45In short, once the world gets back to normal, we’d love to have anybody who is interested out to
00:06:53Come see the lab in person, come meet Erica person, and meet a lot of our scientists and administrative team that would show you that
00:07:01We are all deeply appreciative of the Community support that we received and we are a very open and welcome place to share our great work. So, that being said, I’d like to show you just a few slides.
00:07:15Am able to open this up,
00:07:26Are you all able to see my screen?
Dr. Erica Ollmann Saphire
00:07:30No, I’m afraid we’re not.
00:07:33Let me see.
Dr. Erica Ollmann Saphire
00:07:52So, thank you all. Sorry for for the hiccup. As I mentioned, the Institute is one of the world’s leading organizations, it’s a non-profit, medical research organization focused entirely on studying the immune system.
00:08:07These numbers, given the historic success we’ve had over the last couple years, are small pillars of where we were and we’re already greatly surpassed a
00:08:18Number of things such as dollars that the institute has each year to spend on research and number of employees. We have about 500 employees,
00:08:2921 principal investigators, which are our faculty, which Erica is one of our gems, if not the gem of the Institute.
00:08:37But as I mentioned, we’re right down the street from all of you. And right in the research corridor that many of you are familiar with. We are affiliated with UCSD. So again, please come see us for yourself.
00:08:53Why we are as good as we are, is we have a clear and powerful focus. We spend our days entirely focusing on understanding the immune system and the behavior of the immune system. Why do we do that?
00:09:09For our mission to create a life without disease. We believe understanding and investigating the immune system could
00:09:16Help us understand, prevent, and cure any number of diseases that affects so many of us.
00:09:23We are structured in three centers. I know Erica will talk about this a little bit more in detail, but our three centers of focus are
00:09:32Cancer, and we have a cancer immunotherapy trial, based on the work from one of our researchers underway in the clinic.
00:09:41For example, we have an Autoimmunity and Inflammation Center, which focuses on, as you can imagine, the large number of autoimmune conditions and things such as
00:09:53Heart disease. And lastly, what again we’re going to spend time talking about today and has brought us great attention around the whole world is our infectious disease and vaccine development center, which Erica is a real leader in.
00:10:07Our 21 member faculty, and you’ll see faces you might recognize there in your community, including our president and CEO, Chief Scientific Officer Mitch Cronenberg.
00:10:18And the star of the show, coming soon, Erica. Our faculty are organized in each of these centers to do their work to basically understand the underlying
00:10:30Behavior of the immune system, but also as a way to combine their efforts and combine their brilliance to see how those behaviors might affect diseases, both in the center of their assigned and as well as provide clues to others, working on different parts of the continuum.
00:10:48Back early last year, when the coronavirus affected all of us, we formed a task force of some of our top minds to address
00:10:58Elements of understanding the virus and addressing the pandemic. Which basically Erica will go into detail on,
00:11:06Didn’t mean that we got to put on hold, other work, but instead just add extra work to already a very successful group of people.
00:11:14They’ve all worked tirelessly over the last year to come forward with incredible developments that have really informed the
00:11:21Current vaccines that are out there, as well as all kinds of other therapies and all kind of other clues about the virus that have been helpful to getting us to the more positive position we’re in today.
00:11:34One example of that, and the importance of our work and maybe how we all feel, “Why didn’t I know the institute before?” Well, the good news is lots of the people who are making decisions of this
00:11:45In this country do know who the institute is. Including Tony Fauci, obviously a hero to many this last year for all that he’s done to steer us through this pandemic.
00:11:55When mentioned and when brought to Congress to talk about what’s underway to help us and help citizens of this country
00:12:03Tony, specifically referenced work underway at the La Jolla Institute as the kind of work that’s making a difference that we need more of to help us address the pandemic. So, Congress at the time might not have known about us, but they certainly have since.
00:12:17With that being said, I obviously can’t go on enough about the great work Erica does. The kind of great collaboration she’s built here in San Diego and around the world.
00:12:31As mentioned earlier, she was recently named, and I know ARCS is a group that’s fond to all of us on the call, as the ARCS, “Scientist of the Year.” It’s just the latest addition to her many accolades. So, with that being said, Erica
00:12:46I’d like to turn it to you.
Dr. Erica Ollmann Saphire
00:12:51Thank you, Chris and thank you, Anna. It’s such a pleasure to speak with you today.
00:12:57Chris I’ll need you to stop sharing your slides so that I can start mine.
00:13:01Yes, thank you.
Dr. Erica Ollmann Saphire
00:13:03Thank you to all the Dowling & Yahnke clients for your questions. It’s
00:13:08Certainly what’s on all of our minds. I’ll show you some of what the research we’re doing and the new findings and what we know about the mutations that are emerging.
00:13:19So, this is where we work. Today I’m going to talk to you about our international consortium for antibody therapeutics, where we are in this pandemic with the changes are in the virus, and what we learned about immune defense.
00:13:30Now in the questions that you sent me ahead of time, you asked me things like, why is there so much variation is virus?
00:13:36What are the variants? Where are they in the virus? Should we be worried about them? Will the vaccines protect against these emerging variants and new variants have yet to uncover, but are probably out there?
00:13:48And how do we adapt the vaccines toward these future variants? So, I’ll show you some of my answers in detail, but briefly
00:13:56They vary because of immune pressure and spillover. Mutations in the receptor binding site and more and the other answers are yes, most likely, and yes. Let me walk you through those.
00:14:06So the first thing is that viruses change when they change hosts, change cells. For a novel outbreak virus use a term called spillover.
00:14:17When the virus comes from its natural host or animal reservoir into humans, that’s the introduction of an outbreak. I call that a spillover that’s spilling over into the human population.
00:14:28There’s another term which is spill back. That’s when the virus has been gone from humans back into animals, other animals.
00:14:36And so the spillover is what starts the outbreak. When it comes from the natural reservoir, and it might be something that we’ve never seen before, we didn’t know that virus existed,
00:14:46it infects humans. So, many outbreaks start with mosquitoes biting humans, like Zika, Yellow Fever, Japanese Encephalitis Virus.
00:14:54They start from mouse to human. So lymphocytic colitis, meningitis virus, which causes birth defects, is spread by house mice. Loss of fever, hemorrhagic fever, and in
00:15:04Western Africa and Machado virus in South America spread from populations of field mice or house mites to humans. Other viruses like Ebola and NEPA, are bat to human.
00:15:15MERS (Middle East Respiratory Syndrome) and another coronavirus is camel to human. The first SARS, SARS-1 from 2003, was spread they thought from
00:15:26Civic cats to humans and the spillover events happen when these animals bite humans, when we hunt, or when we butcher them for food.
00:15:36Or also through animal waste, when we get infected with mouse virus is often from a mouse, urine, and a mouse droppings that have been aerosolized in our homes, our cabins, or in our food.
00:15:52Another source of animal waste, for example, outbreaks of up to 90% NEPA virus happen when that waste get into palm sap that is drunk or when humans enter caves in which bats are in
00:16:07Dense population and there’s full of Hantavirus.
00:16:12So, the spill over is what starts the outbreak from forest to humans. Spillback is what propagates the outbreak.
00:16:19That’s when there’s enough virus in humans and humans are shedding enough virus that they spread it to animals, it could be different kinds of animals.
00:16:27It could go back from human to mosquito, mosquito bite and infected human. It could be human to cat, whether they’re domesticated cats for coronavirus or wildcats. It could be human to mink, as we’ve seen this year.
00:16:40Those spill back happens when humans have direct contact with animals. It could be because there are pets, it could be because we are keepers, it could be we’re veterinarians.
00:16:51Or, when animals come in contact with human materials or trash, it’s full of our viruses, or wastewater which is full of our viruses. There is spillover and spillback.
00:17:00The important thing, and why this causes pressure and adaption in the virus, is that when a virus interest in new host
00:17:07It’s under a different sorts of pressures. It has to figure out how to operate in a new cell with different parameters and slightly different receptors and factors.
00:17:15A virus by itself is not alive. It needs to hijack your cells in order to have the materials and factors it needs to replicate and propagate itself.
00:17:25It must understand, use, and hijack all the materials in your cells to propagate its life cycle.
00:17:31If it’s gone from human to mink well, now all of a sudden, it has to figure out how to use the mink receptor instead of the human receptor.
00:17:39And so all the minute little changes that happen as the virus makes lots of little lack of proofreading errors, every time it copies itself, sometimes one of those confers an advantage. But happens upon a mutation that gives it
00:17:51Better ability to anchor to that mink. It explodes in greater amplification in the mink, and greater transmissibility, sometimes that’s the worst virus for us too.
00:18:01When a virus spills in from one species to another, there couldn’t be a flurry of mutational selection where it looks for variants and enhances variants.
00:18:11So, this fall North Denmark was in lockdown over cluster of mutations found in mink farm or spillback from humans to mink
00:18:21And then many more humans get infected back from those mink. They had to call thousands and thousands of mink. They also found mutated virus spilling over into North American mink of those kept for fur and also those in the wild. That’s evidence of spill back.
00:18:37Other kinds of spill back and been in the news. Transmission of SARS from humans to their pet cats, or even the Tigers at the Bronx Zoo, and recently the gorillas in the San Diego Zoo.
00:18:49Any animals with which we interact we should aerosol viruses and then they spell back again, and those animals back to the humans.
00:18:57What becomes a worry is when the virus propagates and the species, whether their species that we keep as pets or as livestock or back in the wild,
00:19:07Because then it can get reintroduced back to humans as well. And so through analysis of mink this fall many, many mutations were found.
00:19:16Not all of them are bad for us. Some of them weaken the virus, that’s fine. We don’t mind those, but we keep an eye on the ones that enhanced transmissibility, enhance separate binding, and evade antibody responses.
00:19:27And what we’ve been doing in my lab is looking at the molecular level about what these changes are and what they mean for that surface spike protein.
00:19:35The surface protein the virus uses to attach the cells. The ones who are most concerned about, are those that enhance the viruses ability to infect us.
00:19:44Now very much in the news, there’s been another source and mutational selection. And that was what has risen in the human to human transmission.
00:19:53So, we’ve now had 93 million cases of the coronavirus. When this novel coronavirus started to emerge, all of us were
00:20:01immunologically naive, meaning we had no pre-existing immunity to this virus. We all looked like fresh meat. It was able to spread essentially unchecked, person to person, continent to continent.
00:20:15It was fairly quiet on a mutation level for the first 10 months. One mutation arose, but conferred an advantage to the virus and became globally dominant within a month.
00:20:28But that was about the only one, but then later this fall, after months of cycling, enough period of time had past and enough humans had been infected, that created the opportunities for more mutation to flourish of clusters and mutation to emerge.
00:20:47One of these, we’ve heard, comes from the United Kingdom. Some of these originally identified in the UK, other ones emerged from South Africa.
00:20:55It is thought that some of this transmission may have occurred through lack of immune control.
00:21:02And so, one episode has been well studied. This emergence of cluster of mutations that look dangerous that emerged
00:21:09Essentially in a cancer patient in the United Kingdom because that cancer patient had a compromised immune system.
00:21:16The virus establish itself in a chronic way. It infected that patient for months, instead of two weeks. Over the period of months and lack of enough immune system control to wipe it out,
00:21:31Give it just enough pressure to try to steer that virus to escape what immune responses there were, and that could have amplified the presence of mutation.
00:21:40There have been suggestions that some of the mutation clusters emerge from South Africa could correlate with a high prevalence there of people infected with HIV one and tuberculosis.
00:21:51When these people are immune suppressed, they can’t clear the virus. It gives an opportunity for that virus to linger in that human for months. When it’s a chronic infection there’s more time
00:22:02For all those little errors that normally happen at a small scale to build up and have an opportunity to select.
00:22:12When we have chronic infection and lack of immune control, we’re likely to see a greater number of mutations arising and then spillover of those mutant viruses into other humans.
00:22:22So, that brings us to another question that several of you asked me. There has been discussion now and if we are limited in the number of vaccine doses, can we get them to stretch further?
00:22:32Can we give half doses of vaccine, is that just as good as a whole dose?
00:22:36Or, can we give one dose of vaccine instead of the two doses, you need one shot and you need another shot a month later, that’s called the prime and a boost. Do we need to give this boost or can we vaccinate twice as many people?
00:22:48The arguments are significant on both sides of that equation. We will find people with just as many degrees arguing on one side and arguing on the other.
00:22:58There are many people who have spent their lives developing vaccines that say that in their experience in other vaccines we have developed, and we don’t know for this one yet, but in other vaccines, we have developed
00:23:10Y’all can get a better immune response if you wait four to six months between the prime the boost.
00:23:15So right now, what has been currently evaluated for the Pfizer and Moderna vaccines is three weeks or four weeks, not four to six months.
00:23:23The reason could be accelerated schedule is that we’re in a pandemic. We may not have the luxury of time to wait six months in order to develop that immunity. So the question is,
00:23:33With that condensed schedule the three or four weeks between first and second shots, between prime and boost, do we get the same antibody response as if we’d waited later?
00:23:43Do we even have the luxury of waiting if we have elderly people and have healthcare workers that are susceptible to an onslaught of virus that it is certainly out there,
00:23:54Can we afford to take that chance? The worry is that if these people are insufficiently
00:24:00Protected, well, then they will develop disease and if they are insufficiently protected, does that just create the petri dish that will encourage more mutation?
00:24:09The answers is it’s just not really know. We don’t have all the data of what happens if we delay six months or what happens if we give a lower dose instead of a higher dose.
00:24:21In some of the clinical trial data,
00:24:24It has been observed that the lower dose of Moderna might have been just as effective, especially in young people with a robust immune response. So there are trials in the UK now
00:24:32Building upon that very small amount of data to see if that’s something that could be used more broadly. Is there a way to stretch the material that can be delivered?
00:24:42There are other studies in progress, particularly for people that are very vulnerable, the immune compromised or the elderly.
00:24:51We don’t want to mess with that protection. My personal thought is that if the clinical trial data on over 40,000 people says that we get 95% efficacy with a certain regimen of two shots a month apart,
00:25:03We need to protect these vulnerable people from what is likely severe disease. We don’t want to mess with this formula.
00:25:09But, for otherwise young and healthy healthcare workers who
00:25:13Might want to participate in a research study at an academic medical center, they could actually collect that data to say what happens if we delay, what happens if we give half a dose instead of a full dose?
00:25:25There were some medical centers that are now doing those trials, so we get that data.
00:25:30The mutations that have emerged are these. There’s one thing called the UK variant, it has another name and more scientific name – B.1.1.7.
00:25:39It first emerged, we think in September. The first human sequences that contain this cluster variations were found the end of September in the United Kingdom.
00:25:51The countries in which that virus was rapidly transported between September and December are the ones that are shown and dark gray or navy blue here.
00:26:00By December, earlier January, it had spread to other continents. So in a very short period of time, before science really realized that these mutations were present in the cluster and spreading, it already traveled around the world.
00:26:17This is where we are, as of, I think yesterday on that United Kingdom variant. It has been imported to the countries where that are light purple.
00:26:29There’s documented human to human transmission that that variant, where it is dark purple.
00:26:34We know it’s documented human to human transmission because people find that they are infected with this new variant, but have no history of traveling, so they could only have picked it up in their local community.
00:26:45So, it is here and it is spreading and has been spreading for some time. The South African variant, which also has another name, B.1.351,
00:26:55Its first known sequence containing this variant from Cape Town was in early October. It first spread, it looks like to Australia and the United Kingdom. Travelers and then by the end of December was in multiple other European countries as well.
00:27:14We have importation as well to North America and Asia, with documented local transmission within the community in southern Africa and also in the United Kingdom.
00:27:28Those two lineages, and also a cluster of mutation that emerged in Denmark in mink, have multiple rotations with them, so eight or nine.
00:27:38Some of these are in common and some of them are different. When the virus doesn’t have mutations in common, that could either be that confers selected advantage, so that it happened to pop up multiple times and stay.
00:27:51Or, because they’re building on top of something that became globally dominant. That second possibility is true for the mutation I’m showing you in blue, D614G.
00:28:01That means that at position 614 and the sequence of spells out the spike protein, it used to encode D. That’s the amino acid as part of acid.
00:28:10And sometime in February a mutation occurred which switched it to G. That’s Glycine.
00:28:17That confirmed the ability of the virus to grow several fourfold more abundantly and that helped it become globally dominant within a month.
00:28:26All of these new variants are now building upon that first mutation. That first mutation D 614 G,
00:28:34That’s something that we published on in August, showing how it first emerged in February and within a month it had become essentially the virus that was spreading around the world.
00:28:44It allows the virus to grow to hire copying, that could help with transmission, I don’t see how it wouldn’t help with transmission.
00:28:51It’s sort of like a corn plant, but now grows three to nine years instead of one. There’s just a lot more corn and that’s why this has become globally dominant.
00:29:01Now fortunately, that one mutation didn’t seem to affect the ability and antibody to an activated. If anything, it was a little easier to neutralize.
00:29:11We weren’t as worried about it evading immune response there. The worry was that it made the virus fitter. The other mutations have now emerged on top of them. One a particular concern, that’s an all of these variances is N501Y.
00:29:26That’s at position 501 in the spike protein. It used to be sparging N and is now piracy Y.
00:29:35That mutation occurs exactly at the site or the spike protein in red,
00:29:41Interacts with the human receptor called ACE2. So, this is the crystal structure, the x-ray crystal structure looking at the molecular interactions of the surfaces by which virus sees human, anchors on it starts the infection process.
00:29:56A substitution or a change, a one letter change that changes that one little tiny piece of chemistry allows the red spike protein to anchor more tightly to the receptor. It helps infection.
00:30:10That has been such an advantage for the virus at the same random mutation event has occurred and been selected, settled on, and propagated multiple times independently.
00:30:25That same mutation emerged in research mice, housed in isolated box. It emerged in people in the United Kingdom. It emerged in different people in South Africa.
00:30:35Related mutation emerged in mink and also in humans in Denmark. So selection of that position gives an advantage to the virus and it’s such an advantage that
00:30:47That random event of a change at that site has happened and been selected multiple times in multiple places. The worry about this one, is that it seems to make the virus more effective, more transmissible.
00:31:01The other worries are these two. By changing the surface chemistry on that red protein, we not only changed its ability to bind receptor, binds receptor better,
00:31:13It might bind antibody worse. A lot of antibodies work by inactivating the virus. One way in which they inactivate the virus is to anchor on to exactly that red thing, exactly that red place.
00:31:25By covering up the receptor binding site is antibodies could prevent a virus from attaching to it’s ACE2 receptor and entering the cell.
00:31:34But many of those antibodies might need that original amino acid, a position 501 and we’ve gone to change it. We’ve changed the chemistry of that surface those antibodies might no longer bind.
00:31:45So, by changing the virus, we might have now escaped some portion of the antibodies against that site. The second thing is this, that we’ve altered the kinetics. So it’s always a race, a battle
00:32:00Between the ability of the virus to infect and the ability of the immune system to tamp it down. If we’ve conferred an advantage to the virus, it might outpace the immune system.
00:32:11If we’ve conferred an advantage to the virus for its speed and strength that which can attach to an entry your cells, we might have out competed the ability of the immune system to defend it. What we may certainly have done, by accelerating the virus, we might
00:32:27threaten the pace by which humans can deliver vaccines. If we have accelerated the speed of the outbreak, if we’ve increased the number of people that get infected from any other infected person, if we increase the likelihood that somebody will get sick upon being infected,
00:32:46That outbreak number of cases start to accelerate. It’s threatening the ability that by which we can deliver vaccines to deliver protection.
00:32:56The important thing to know is that there are now multiple clusters of mutations that have emerged in this human to human transmission.
00:33:03We have many clusters that have emerged in many parts of the world. There are 20 documented clients of the virus or 12 that are co circulating the more successful ones tend to take over and the weaker ones tend to go extinct.
00:33:16There are new variants, which had just been sequenced in Brazil and elsewhere, and I’m sure there were more that are currently circulating that just haven’t been sequence yet.
00:33:25So the major question on all of our minds is, “Which antibodies still work?” The antibodies elicited by your vaccine are listed by your first protect your infection protect you.
00:33:36Will the antibodies that we’re delivering as intravenous therapeutics still work? That is the key question that my lab has been focused on.
00:33:45Many of you asked about that and many of you asked about the status of my antibody consortium.
00:33:49So the consortium that I’m running is this, the Coronavirus Immunotherapeutic Consortium is called CoVIC.
00:33:55The goal of CoVIC was to compare everybody’s competing antibody therapeutic, side by side, figure out which are best, what makes them best, and which ones we want to deliver as drugs. Antibody therapy is like
00:34:08Anti-venom. When you get a snake bite, you go and get a shot of anti-venom. That is an array of antibodies against the snake toxin. They immediately seek out, anchor on to, and activate that snake toxin before it can do its damage.
00:34:24That will prevent that snake toxin from amplifying the disease. You know, with a snake bite you want the anti-venom right away. You don’t want to wait until your leg turns purple.
00:34:36The same thing is true with antiviral antibody. If you get bitten by a rabid dog, you get antibody against rabies virus and you want it right away. You want the antibody to seek out and destroy the virus and alert your immune system to control it,
00:34:48Before that infection has taken place. The same thing is true for antiviral antibody. If you don’t already have antibody against the novel coronavirus, because you haven’t been infected and you haven’t been vaccinated or maybe you’re immune compromised,
00:35:03You can get
00:35:05Effective antibody. In fact, more effective antibody than you may have made yourself through intravenous drip. The way we do this as we look at the immune response of survivors and then immune response in the survivor there are
00:35:18Billions and billions of potential antibodies against all sorts of different things. We can search through and find the needles in the haystack find us the one or two
00:35:25Absolutely most potent ones that could rapidly and activate coronavirus. You can scale them up and deliver them in a very precise way. Essentially get
00:35:35The immune response of a rock star in a couple of hours, instead of needing a month and a half to develop immune response.
00:35:42It’s slower and it’s expensive. So it’s not practical to deliver to millions of people, but it’s a key life saving therapeutic option.
00:35:49It also gives us a lot of information, by understanding how the very best antibodies work, we can look and see if vaccines are listening, those kinds of antibodies or people that have survived infection or listing those kinds of antibodies.
00:36:02I’ve been tasked to figure out what the best antibodies are and how we can make them available to people that have become infected because they weren’t vaccinated or yet vaccinated. People that can’t be vaccinated, like pregnant women or people with some
00:36:17Imune compromise conditions or people who were vaccinated, but the vaccine just didn’t take.
00:36:25The goals of this program are to get all the competing therapeutic products from 50 to 70 different companies and compare them side by side.
00:36:33Everyone will think their therapeutic is the best, but we want to put them on a level playing field and make an apples to apples comparison. Do an independent analysis to figure out what’s best and why what makes them best.
00:36:42Make sure that we can find ones that are affordable enough that we can deliver them anywhere in the world.
00:36:47Because with a rapidly propagating respiratory virus, we aren’t safe here unless people are safe everywhere in the world. There are places in the world where people can’t social distance, they will starve to death.
00:36:57If there is no immune protection in these regions, the virus will continue to boomerang and circulate around the planet, so that’s the key goal.
00:37:04While we’re at it, while we have gone to all the trouble getting be competing companies to agree and get that resource of candidate therapeutics to compare side by side, you can actually build a lasting body of information
00:37:18Of what constitutes effective immune control, effective therapeutic mechanisms against this virus. We can look in this database account of different antibody therapeutics and figure out
00:37:29Which ones are going to be most durable, which ones are most resistant to those mutations, which ones are lost when mutations that a certain city have emerged, and which ones we can still deliver. So we want to get that body of information.
00:37:42So right now, we’ve been able to get 239 different mAbs, is monoclonal antibodies, 239 different competing anybody therapeutics and consortium is growing.
00:37:52They have been donated to us from people on four different continents. From everything from academic labs and nonprofits, to the major multinational corporations that are household names.
00:38:01The data that we’re generating in my lab is being used by Operation Warp Speed and the foundations in the clinical trials to help understand which ones we should be investing and analyzing.
00:38:14The workflow for that international effort is this, that all the antibodies come into my lab are all given a code name to make it very fair.
00:38:20Then we distribute these antibodies to multiple experts in the world that are each the best at figuring out one aspect of antibody function.
00:38:28They collect all that data that we put it back together into an immediately publicly available database in order to
00:38:34Look at a multifactorial way. But how does the antibodies working and understand which ones are best?
00:38:40So in this database, we’ve been able to rank order the therapeutics by how well they anchor to that surface spike protein, how well they neutralize viral infection.
00:38:51We’ve been also able to do this, this is what is important for understanding what will be resistant to those mutant varieties and what will remain durable.
00:38:59We’ve been able to sort all these antibodies by what footprint they have in the spike.
00:39:05So I’m telling you, multiple molecular structures that we actually have, we have very powerful microscopes in my lab they’re 11 feet tall.
00:39:11They shine an electron beam down so that we can now see things that used to be so microscopic now come within view.
00:39:18And we can directly image that surface protein of the coronavirus spike. It’s shown here in white, that’s its molecular surface and then the colored ribbon underneath, the red, blue, and green, that is the
00:39:33Chain of the genetic information that’s been translated into the folded up polypeptide code. It’s been coiled up into that certain shape as a certain surface chemistry.
00:39:43The antibodies that have anchored on to the spike are each one of these different rainbow colors. That’s the business end of the antibody, the antigen binding fragment anchored on, you can see they all approach it
00:39:54In different ways and they hit a different footprint. We can sort them into neighborhoods and clusters. That’s the kind of rainbow map on the left,
00:40:02To find out which ones anchor to different places. By understanding which ones anchor to different places we can understand which ones are and are not susceptible to different mutations that have emerged.
00:40:13So what you see here, is looking at each individual mutation that has emerged in this set we’ve looked at, or that emerged in combination. We can look and see which type of antibody is or is not still effective.
00:40:25If it’s boxed in pink, we’ve lost that antibody or lost a lot of activity. We need to deliver a lot more of a dose to still get to work.
00:40:33But if it’s green, the antibody has actually improved its ability to neutralize in the presence of that mutation.
00:40:41We can go through them and confined which therapeutics are still valid in certain regions and which therapeutics are resistant to those escape mutations. Those are the ones that we want to deliver going forward.
00:40:51These are some of the ones that look like they’ve gotten better, more effective, or haven’t been heard by the changes and buyers. Those are the ones we want to deliver
00:41:01Many of you asked me at the vaccines will still work in the presence of these mutations that are emerging, and I think they will.
00:41:08The vaccine makers have evaluated the sera, the blood, the population of antibodies and the blood of people that have received those vaccines. Those antibodies can still
activate the mutant viruses, or at least viruses bearing the
00:41:23Key mutation that people were most concerned about, the N501Y. Testing is still in progress on the complete variant with all eight or nine substitutions.
00:41:32The reason I think that the vaccines will mostly still work is this, that
00:41:38antibody mediated immunity, in what’s called the polyclinic level, many clones, the whole array of different antibody responses that are in your blood or after you’ve gotten a vaccine or after you have survived an infection.
00:41:51It’s not a light switch. It’s not on and off. There’s thousands and thousands of different kinds of antibodies in there, just like you saw those molecular structures with all the rainbow coloring every one of them hit two different spot.
00:42:03You might lose a couple of mutation, but you still have all the rest.
00:42:07Antibody immunity is not an all on or all off light switch. It’s more like a dimmer switch or you might lose a little bit,
00:42:16But you still have the rest. You might dim 5%. In fact,
00:42:21Vaccine mediated immunity or natural immunity is more like not just one dimmer switch, the whole panel of dimmer switches, because in addition to antibody immune response also has different kinds of T cells, different kinds of a native invitation.
00:42:34Depending on how those different dimmer switches are correlated, you know, all of them on, that’s a lot better than only some of them on. A couple of mutations will dim some of them a little bit, but you may still have enough light.
00:42:48We actually looked at that question. We took 48 convalescent sera. That’s blood from 48 people that live in San Diego, they got infected earlier this winter and then got better.
00:42:59Of those 48 convalescent patients, 40 of them had antibodies in their blood that can neutralize the virus. Eight of them did not have antibodies that can neutralize the virus.
00:43:09We look to see, of those sera, which ones were still effective against individual mutations, one at a time. That’s the green and purple. You see there’s really not much difference. They all cluster, about the same. The sera seem to work just fine, if there’s any one mutation.
00:43:27The worry with the clusters of mutations, eight or nine emerged in the United Kingdom, South Africa, and other variants is that by adding more and more mutations you knock out more and more antibodies.
00:43:40So when we put the first four together to build these clusters, we can see that we start to lose some of these sera. There’s not much effect for any one mutation, but there is an effect, we can get cumulative mutations. About 20% of the sera lose maybe half of their activity.
00:44:00So for many of them, there’s not much difference. 80% of people’s sera that started out neutralizing still just fine,
00:44:07But there’s a minority that are worse. Over the scope of a pandemic and a vaccinated population, many of them will not see a difference. Some will see that dimmer switch turn a little bit.
00:44:21So, others of you asked, “Should I get the vaccine if the virus is changing or should I wait for a different vaccine?” I think you should get whatever vaccine you can get as soon as you can get it.
00:44:32And the reason is this, with no vaccine it is a light switch. It is off, you have no immunity. You are fresh meat to that virus. With a vaccine, you do have an immune response on board.
00:44:45If the vaccine is a perfect match for the virus that you might get infected with, the sequence hasn’t changed. It’s 100% dimmer on all the way.
00:44:56If a few mutations have populated, you just turn that dimmer switch a little bit, but you still have everything else. You still might have 90-95% of the light and that’s going to be enough to keep you safe. So get whatever vaccine you can get as soon as you can get it.
00:45:12Can they adapt the vaccines? Yes, they can. One of the chief advantages of this new mRNA vaccine is it the physical material, it’s
00:45:22Part of the vaccine that just the messenger RNA is easier to manufacturer and easier to change right away.
00:45:31They could make a different sequence in maybe six weeks and the question is, how much testing do we make. They can’t just
00:45:38Automatically inject a new thing. It does have to go through some testing, but it may be able to be tested more rapidly or not need so many 10s of thousands of people.
00:45:47So that could be changed. If we have coronavirus for a long time, we might think about having a seasonal coronavirus vaccine that’s matching whatever that year’s virus might be.
00:45:59Many of you asked other things about the vaccine. So if I have allergies, should I worry about getting the vaccine?
00:46:06The allergic events to the vaccine are exceptionally rare. It’s I think .007% of people, but it’s not zero.
00:46:14If you are a person prone to anaphylaxis, if you have an anaphylaxis reaction to, you know, nuts or selfish or something like that
00:46:23You will want to have somebody watching
00:46:25After you get that vaccine. Most of the vaccination centers and doctor’s office do have to park and they watch you for 15 minutes to make sure that there isn’t a reaction. If you have an Epipen, bring it.
00:46:36For the vast majority of people, 99.9%, there’s no no adverse reaction. Many of you asked about the side effects of the vaccine.
00:46:45The way to think about it is that the side effects are really the effects, the job of a vaccine is to mount a immune response. You want your immune system to see this thing as foreign so that mounts a response.
00:47:01The benches vaccine is that you’re showing the shape and surface chemistry of the foreign thing in a way that won’t infect you, won’t cause disease.
00:47:11But when your immune system is building its immune response to protect you, you will get things like a sore arm, a headache, and maybe a light fever. Those are
00:47:23hallmarks that you are experiencing an immune reaction and you want that. You want an immune reaction to your vaccine. You want it to develop an immune response. If you don’t have immune response, you don’t have the immune protection.
00:47:34So it’s common with this and all shots. Your arm might I hurt a while, you might have a headache, and might be a little tired.
00:47:42That’s your immune system working to give you that protection on board.
00:47:48Many of you asked about adaptive vaccines and the durability of the vaccines. Will this vaccine still protect me all year?
00:47:55You know, we’ve only known about this virus for one year and so our duration of protection information is only one year.
00:48:03For other related coronavirus, is quite individual. There were some people that still have antibodies to that SARS-1 infection that they got 20 years ago. There are other people for whom that response waned.
00:48:13There’s also different ways you can measure the antibody response. If you look in circulating blood that’s circulating antibody, but you have another pool, that’s your memory response.
00:48:23That memory response won’t register just in the circulating sera,
00:48:27But it’s there. You don’t want to have high levels of circulating antibodies to every possible pathogen. Then ones you’ve ever been exposed or ever been vaccinated.
00:48:39What you do is you have one circulating for which you’ve been recently infected on a smaller level of the other ones.
00:48:45Your memory response will rapidly amplify by remembering this immune response to some other pathogens, as soon as you are exposed or re-exposed to it. So even if the antibody seems to have waned or diminished a little bit, and sera circulating antibody, you may still have that immune response.
00:49:04I expect that the multi clone, multi antibody response will be durable if enough mutations seem to propagate and continue to accumulate over the year, the vaccine makers will probably adapt their vaccines in order to make a better match. And they do that every year.
00:49:21Now, others have you asked, “If you have been infected before, can you be re-infected with coronavirus, how often does that happen?”
00:49:29And the related question, “If you’ve been infected and gotten better, could you still spread it to someone else if you’re not sick yourself?”
00:49:37Those are really good questions.
00:49:39On the subject of reinfection, a new study just came out where they looked at 6,600 healthcare workers in the United Kingdom. Of those 6,600, which they followed over five months, are 6,600 people that got infected, got better.
00:49:52They followed them for five months, 44 got re-infected, so that’s 0.7% of them. 99.3% did not get re-infected, but some did.
00:50:03And so it happens. It’s something that we need to know about because you cannot assume that you are fully protected always and you might spread it, but it is more the exception than the rule.
00:50:16There’s two different things here. Does the vaccine protect you from disease? Does the vaccine protect you from infection? Those are different.
00:50:25Diseases when you’re really sick and your life is threatened or you have enough symptoms that you’re coughing and spreading more virus into the air. Infection, well, we know you can be asymptomatic and have a lot of virus replicating and have no idea, you can still share it.
00:50:40The way that viral infection works, let’s say you’ve been vaccinated against polio or measles, and a couple years later, you come across or measles.
00:50:47The virus might still infect one or a couple of cells, but your rapidly amplifying memory immune response will take care of it.
00:50:55You will be technically infected, but it’s just a couple of cells. You’re not contagious.
00:51:02If you ask the precise question, “If you’ve been affected before, can you get infected again?”
00:51:07Yes, if you come in contact with coronavirus you probably will get infected again. One or a couple of cells will probably get infected, but your immune response should clear it.
00:51:18Some people that original immune response was insufficient and they got sick again. For other people, the question is,
00:51:26We don’t know the extent to which everybody’s individual immune response keeps control of the virus. We don’t know always whether or not someone is
00:51:36Controlling that virus enough to prevent spreading it to others. While most of the population is still unvaccinated or what we call immunologically naïve. They’re still susceptible, we want to be careful to make sure that we aren’t amplifying the outbreak.
00:51:53Others have you asked, “Which vaccines should I get? Should I get the Moderna or Pfizer? Which one of those is better for older people? Do they work well for all races?”
00:52:02The really practical answer is that
00:52:05You probably won’t get a choice. We are so limited in the numbers of vaccines that we have that your choice maybe take it or leave it, not Moderna versus Pfizer. You might just get the only one that’s available.
00:52:19The Pfizer/BioNTech vaccine, their data suggests that it’s about 95% effective. The Moderna, the data is 94% effective. So very similar. But Pfizer vaccine delivers a 30 microgram dose, two shots, 21 days apart. The Moderna vaccine gives you 100 micrograms dose, two shots, 28 days apart.
00:52:40Some of their original data look like the efficacy was just a touch lower in older people for the Moderna vaccine, but it was a very small statistical sample. So it’s hard to know if that’s real or that’s just the noise.
00:52:52I think they’re very similar, and I think either one would be fine. The data and the clinical trials suggest that they work equally well for all races.
00:53:00It challenges at both of these need what’s called a a cold chain. They have to be kept in the freezer and really a deep freezer, a negative 80 Celsius, colder than our kitchen freezers.
00:53:10Maintaining that cold temperature is kind of a challenge. You know, they’re perishable, they expire, especially going to be hard to try to deliver them extensively around the world and in
00:53:22Developing nations. Also through a lot of parts of this country, it’s hard to find minus 80 freezers.
00:53:31What I do know, I can’t really answer which vaccine you should get, you should just get the one that’s available, but I can’t say what a vaccine you should not get.
00:53:39I would say the one you don’t want is the inactivated virus vaccine. So a lot of you asked about that. That’s the Chinese and Russian inactivated virus vaccines.
00:53:48I don’t think those are as good. In fact, today’s suggestion is not. The reason is the process that happens in an activation, what it actually does, those are shaped changes and that surface spike.
00:54:00This is the surface protein with the virus that uses to anchor to the ACE2, this is the one which your antibodies bind. The antibodies recognized particular shape and chemistry, given the wrong shape antibodies don’t bind and the antibodies don’t work.
00:54:15That spike protein on the surface of the virus is a spring loaded mechanism.
00:54:19It starts in one more compact shape and then it springs forward as it infects the cells. We call those before membrane fusion and after member infusion, before and after.
00:54:30It’s very much like this, where it’s a spring loaded thing that irreversibly drives for to infect your cells. The job of antibody,
00:54:38Is to lock that mechanism together, much like the club in your car, that the binding of that antibody to anchoring on to the mechanism would prevent that springing a spike.
00:54:48The trouble with the inactivation process is it goes ahead and springs all those spikes. So what’s shown to your immune system, the before the compact one is light blue and the after, the strong one and an orange are different shapes and different surfaces and different chemistries.
00:55:05If you vaccinate with something that’s mostly the wrong shape, you will elicit mostly the wrong antibodies. That’s actually been shown by direct imaging the process of those spikes.
00:55:15The inactivation process doesn’t give you the right kinds of antibodies and their classic vaccine studies have challenges with the
00:55:21Early Development of vaccines. For example, respiratory syncytial virus, which causes respiratory disease in newborns and could be life threatening for preemies,
00:55:29Where the inactivation process put all the wrong shape on the surface of the virus, so you lost the kind of antibodies you’d want to have.
00:55:37It is true for this kind of protein. The spike protein of coronavirus and all other viruses like this, the stability of that jack in the box is a problem.
00:55:48So how did the mRNA vaccines get around it? Well, they do one thing, they don’t make the protein itself that would spring. Instead, they just take the one gene that encodes it.
00:56:00They package that one gene and lipids, like a tiny microscopic oil droplet. Those lipids will enter some of your professional immune cells, whose job
00:56:11Is to then make that red protein and show it to their immune system to make that response. It’s very safe. That’s what they were designed to do. There’s no virus there, it’s just the piece of the immune response, ready to go against the key piece.
00:56:28So your spikes and more likely to be in the right shape because they haven’t been inactivated through any external chemical process or heat.
00:56:37But it’s still a challenge to get your own cells to make them the right way. There’s a couple of tricks that have been used to try to get it to do that.
00:56:45The very first idea, that’s what’s in the Moderna and the Pfizer vaccines, something called to 2P.
00:56:51It’s introducing two proline residues, those proline amino acids introduce little kinks that help anchor the protein in the right shape.
00:57:01The second generation idea is something stronger than that which is just a staple, just a molecular staple. It’s a disulfide bond introduced a staple to the top of the spike hold it in the right shape.
00:57:13We have now improved upon that idea even further by moving the staple and making other changes so that it is rock solid in the right shape.
00:57:23Better presents the right structure, especially the parts that don’t change and better displays the right sugars that coat the virus which immune system needs to understand how to obey.
00:57:33So that’s the third-generation vaccine candidate that my lab is working on and the really exciting thing about it is that it’s stable at room temperature. It’s not susceptible to the cold chain problems that others are.
00:57:45We can also use that molecule as a tool to discover better antibodies. So the challenge with a mutation variance and the challenge with
00:57:53Coming up with seasonal return at this virus and the challenge with having vaccines and therapeutics and respond to the changing virus, is
00:57:59That it’s changing. Most of the current therapeutics target that top part would anchors to the cell. That’s the part of the virus changes that sequence the most.
00:58:10The bottom, this isn’t the machinery, this is the jack in the box machinery, doesn’t change. It’s critical for the virus to not have errors there.
00:58:19Again the antibodies that anchor on to that machinery, they’re going to be less susceptible to mutation escape, but how do we find them.
00:58:27So my lab is particular tool and particular strategy for this. We are protein engineers. We have engineered that copy of spiked that hold the better shape and show the better surface chemistry.
00:58:38We can use this for precise molecular recognition experiments. We have this machine called the “Beacon”.
00:58:44Inside the Beacon there’s something the size of a postage stamp, which is a microfluidic cell.
00:58:49And we can use light to separate individual B cells, those are the cells that make each one single antibody and separate them into individual little holding pens.
00:59:01Then we can interrogate those cells and ask each individual cell if they make the certain kind of antibody that we will want.
00:59:09Do they make an antibody that’s resistant to mutation? Do they make an antibody that will prevent other coronavirus diseases can occur, and other infections as well.
00:59:16And making it light as a signal beacon, the beacon to light up the position of the one cell we want, that makes the one anabolic sequence that we want.
00:59:27Then we can use light again to decide which is the one antibody that we want to study, lifted out, analyze it, and make more of it as a therapeutic.
00:59:38We’ve done a proof of concept on a similar virus that has a similar sprinting right mechanism. We can take
00:59:43preparations of that surface spike that are the shapes we do want and don’t want and look at all the different antibodies and say here’s one. The antibody binds right thing and wrong thing.
00:59:54We have this antibody, this is the one we do want. It’s the one that holds the molecule in the right shape. It prevents that jack in the box spring.
01:00:02We have other antibodies that only recognize things that we don’t want with the long shape. So we’re using that kind of technology to now to sort for ideal coronavirus antibodies that will fit into an improve upon, those are already in the global consortium of therapeutics.
01:00:18So what I’ve shown you today is we’re leading a global effort to figure out what antibody therapeutics work best and why.
01:00:26We’re looking at 244 therapeutics from four continents. We’re sorting them out by where they bind, how well they work, which are and are no longer susceptible, or no longer
01:00:38Effective against the emerging mutations and we’re engineering portions of spike is a better vaccine at a better tool.
01:00:44These are the folks on my research team and I really want to thank them for all of their effort,
01:00:48Days, nights, and weekends against this pandemic. Particularly Dr. Sharon Schendel, my Program Manager for the CoVIC consortium.
01:00:55Kate Hastie leading up the antibody discovery effort, Eduardo Olmedillas, Colin Mann, Haoyang Li, and Vamsee Rayaprolu helped with so much spike engineering. And all the different labs and contributors and the CoVIC Consortium.
01:01:07 I will stop sharing and I’m happy to answer any other questions that you have in time that remains.
Anna E. Diaz
01:01:14Thank you, Dr. Saphire. My goodness, a lot of really good information.
01:01:19It’s amazing how far we’ve come. This is our second webinar together, which we so appreciate and we weren’t close to vaccines back then. So, you know, we definitely have entered a new chapter.
01:01:28We’ve got a lot of questions have come in. So I’d like to start if I could with you.
01:01:33The first is, people are very curious, have you been vaccinated and if so, did you have a choice? If so, what did you choose and why?
Dr. Erica Ollmann Saphire
01:01:43Not yet, I have an appointment as an essential worker and I’ll just get whatever is on offer at Petco. I don’t know what it’s going to be. I think, Moderna.
01:01:51I went for the take it and leave it options.
Anna E. Diaz
01:01:56what you described, that’s right. Okay, next question. So is the type of mutation you’re describing with COVID-19,
01:02:02Typical of any virus or more worrisome then the typical viruses we seem to handle?
Dr. Erica Ollmann Saphire
01:02:07It’s common. All viruses mutate, they all make errors when they propagate. Now, the rate of coronavirus is slower. It’s rated mutation is about half that a flu, 25% of that of HIV that has some capacity to fix its own errors.
01:02:20But with 93 million infections, it’s just propagating. All viruses do this, all viruses drift in their sequence and evade immune responses.
Anna E. Diaz
01:02:30Thank you. Okay, so a couple questions around this topic. What danger are children facing without the benefit of vaccines as they interact with other children in schools, camps, summer activities, friends, etc.?
Dr. Erica Ollmann Saphire
01:02:43We don’t have approval yet for the vaccine for children.
01:02:48Nearly all children experience much more mild disease then adults. So adults, especially elderly adults are the highest priority to vaccinate. But children certainly can
01:02:58Get it and get infected and there are some that are immunocompromised, and it’s more dangerous for them than others.
01:03:04It is more rare for a child to spread it to an adult, than adult to spread it to an adult, but
01:03:12We do want to protect our kids and we send our kids to school with a couple hundred other kids and we want them to see their friends. That’s something we need to definitely move toward. Is their life as threatened as an older adult? Mostly not, but some are
01:03:29immuncompromised, some are cancer patients, and sometimes you don’t know yet that your child has a disorder.
Anna E. Diaz
01:03:38Thank you. Two questions that are kind of interrelated here. If vaccinated individuals can still spread,
01:03:47Even though they’ve had the vaccine, should we be getting tested to see if we are asymptomatic spreaders? The next related question, “Is there any chance you can spread the virus to someone, even though you’ve had a vaccine?”
Dr. Erica Ollmann Saphire
01:04:00If you’re vaccinated, you’re much less likely to spread the virus then someone who has not been vaccinated,
01:04:06But it’s not impossible. For a lot of us, for example, for me to be able to go to work, I must be tested frequently to make sure that I’m not an asymptomatic spreader. So, those of us that are
01:04:17Going to work or are essential workers will still be tested to see if we are or are not asymptomatic spreaders. I think if you have been vaccinated, before going to work, you’re interacting with other people even masked and
01:04:30Especially if you’re seeing elderly people, you will want to make sure that you aren’t inadvertently spreading the virus. You’re much less likely to, but it’s not
Anna E. Diaz
01:04:42That’s great to know that.
01:04:45The next question, Is there value in convalescent sera for people who had an asymptomatic Covid infection?
Dr. Erica Ollmann Saphire
01:04:56Convalescent sera is the first thing you have before you have discovered more potent antibodies. It is usually less effective than a monoclonal antibody therapy.
01:05:07It may be more available to go into developing nations, but we don’t have the access to these more precise therapies, so it could help.
01:05:15If someone is asymptomatic, though, they are less likely to be a candidate for treatment and someone who is getting ill.
01:05:25So one could use convalescent sera here to treat asymptomatic, but of course it’s limited in supply right there’s only so many convalescence really have so much blood to give.
01:05:36So it’s possible,
01:05:38But it’s probably not the highest priority treatment to be delivered.
Anna E. Diaz
01:05:44That makes sense.
01:05:46So two additional questions, somewhat again interrelated. There are some longer term impacts of having Covid that are being talked about. You know, cognitive and other related issues. What are your thoughts around that?
01:05:58How does that connect to vaccines? A related question is, Do you have any sense of what the long term health risks risks are of the vaccine, say, five to ten years from now?
Dr. Erica Ollmann Saphire
01:06:11It’s the long term effects that are really the concern, aren’t they? The 40 year olds that are throwing clots, or the 40 year olds that
01:06:21Become long haulers for one reason or another, and they’re foggy headed and have long term complications. That’s why we need to be
01:06:31So careful. It’s not merely just surviving and you want to make sure that you haven’t compromised your health and ability to work and care of your family in the long term.
01:06:42What was the second part of the question?
Anna E. Diaz
01:06:46It was, how do the vaccines impact either managing those longer term impacts, the long hollers? Also as the vaccines themselves. What are any delayed impacts five to 10 years from now, having taken the vaccine? Right.
Dr. Erica Ollmann Saphire
01:07:00If you’ve gotten the vaccine, your vastly less likely to get infected and then your chances of becoming one of those long haulers is a lot lower, right? You don’t to prevent infection from a disease, you’re less likely to have the virus establish itself as a chronic infection.
01:07:17Five to ten years out, I would expect that you will still have some immunity against SARS-CoV-2 to from these vaccines. I’m, I’m not expecting
01:07:28Any long term consequences. Instead, I would expect a long term benefit. I don’t think we’re done with Corona viruses. I think there’s very likely to be a third one. This one that’s likely to have seasonal return.
01:07:38There’s just so much of it on the planet right now, it’s not going to go away.
Anna E. Diaz
01:07:43Not anytime soon, yes.
01:07:46This is actually to your comment just made, this somewhat similar. Will the methods used from this Covid vaccine, obviously we’ve we’ve come up with a vaccine so quickly. I mean, historically, it’s incredible how that’s come out.
01:07:58Do you think some of the new science from that will help improve flu and other vaccines in the future?
Dr. Erica Ollmann Saphire
01:08:04I think it will. So this is the first time we really launched a vaccine made from mRMA in a in a large scale.
01:08:09Our flu vaccines are often amplified in chicken eggs and that’s not ideal because it takes a long time to make the thing in chicken egg. Some people are allergic to chicken eggs.
01:08:19Sometimes mutations occur in the egg itself that make the vaccine less efficacious than vaccines that have made other ways. We can definitely stand to modernize many of our vaccine development methods.
01:08:33So, the mRNA is good because you can do it really fast, these vaccines have come out in a year. The fastest we’ve ever made vaccines before was four years or months. Typically it’s 10 years.
01:08:43We can make something quickly we can respond to the next pandemic or we can more quickly change.
01:08:48You know, flu vaccine protection is correlated to how well that vaccine matches the type of flu virus that will spread.
01:08:56The years when it’s poor match you get poor protection, more illness, more death. Good match, good protection. So if we had
01:09:05Vaccine platforms that you could turn around more quickly, you would have a better idea what the emerging viruses are going to be and have time to make the vaccine or change the vaccine.
01:09:16It’s a really good idea for that purpose. What we now need to see is how long are they going to last? Are they going to last, give us lifelong immunity, like our MMR vaccines, measles, mumps, rubella,
01:09:29Or it’s getting more transit? Where we have to get vaccines every year and just you know you need five years to see what the five year effect is going to be.
Anna E. Diaz
01:09:41Another question, if we could. If you have an immune deficiency, is it safe to get the vaccine? You talked about that, but maybe you can expand on that. What about those going through immunotherapy treatments?
Dr. Erica Ollmann Saphire
01:09:54So the reason why many of you know deficient people cannot get some vaccines, is that some vaccines are made, not from one harmless piece of the virus, but instead from a weakened virus or an attenuated virus.
01:10:08That virus is in some vaccines, not these, but other vaccines for other viruses intended to be weakened enough
01:10:17That it will infect your cells and propagate for a couple of cells, but it’s something your immune system will rapidly be able to control.
01:10:24Their are benefits about that. It looks like more of a threat to your immune system, you might mount a stronger response.
01:10:29But what’s weak in you and me, isn’t weak in immunocompromised person. So that virus could actually be a threat for them. So that’s why they can’t receive those kinds of vaccines. Can immunocompromised person get an mRNA vaccine?
01:10:45I think the best thing to do is to talk to your doctor that best understands exactly what your particular condition would be.
01:10:52This kind of vaccine doesn’t present the threat that a weakened or attenuated replicating virus vaccine would, like the Adenovirus vaccine.
01:11:01So it might be that it’s more appropriate, but you’ll have to talk to your doctor about your particular condition might be. If you’re on immune therapy for something else, again, just talk to your doctor about what the different
01:11:17Things we should consider are. Definitely if you’re immunocompromised in any way, you’re more susceptible to COVID-19 illness than other adults. So you’re more in need of immune protection than other people.
Anna E. Diaz
01:11:33Thank you. One of the comments you mentioned our educators on earlier was as the mutations occurs, it’s possible that vaccines will be released to deal with those those new mutations.
01:11:45Do you envision that those vaccines will have to stack on each other or will you have to take the brand new one that’s been just released because of mutations? How will that sequence work do you envision?
Dr. Erica Ollmann Saphire
01:11:58I don’t know. I think they need to work out how much testing they’re going to need and how long that will take.
01:12:03You could picture a scenario where the Coronavirus vaccine is tuned every year to what the expected emerging sequences are. Or, maybe instead of containing just one viral sequence, maybe it’ll contain three, like your flu vaccine often has three different kinds of flu in it.
01:12:18If they could anticipate what might emerge and come your way, they could dial that in every year.
01:12:26But there’s lots of things that we need to understand on how much testing do we need every time we make a variation. How long does this immune last, is it lifelong? The people that have gotten that first sequence, which is the original Wuhan sequence with the two proleans,
01:12:41Are we still protected next year with all the drift from the cumulative mutations. If they’re still protected, then changes may not be needed. If they’re not protected, then that would inspire the need to develop new kinds of vaccines or complimentary kinds of vaccines.
01:13:01Great. There are studies for other viruses, where people got a stronger, more robust immune response by having different kinds of vaccines. So if the prime with one type and boost with another
01:13:12they got a better response than two of the same. We don’t have that data for Coronavirus yet, but we have that data for people with HIV, some other viruses. Okay.
Anna E. Diaz
01:13:23Well, this will be probably our last question and a lot of people were really excited about the antibody consortium and the work that you’re doing there. What else do you need right now to advance that important research?
01:13:36The perspective of what does that chapter look like next for that work?
Dr. Erica Ollmann Saphire
01:13:41We need to support the salaries of the postdocs and technicians that are actually doing this work.
01:13:47The more mutations we can study, the better that body of information is. If we have the information the database about this therapy will or will not work in San Diego, we can better deliver the right thing.
01:13:59Then I need a piece of automation bad and my microscope is going to let it run overnight for us. We don’t need a hands on and a more slower throughput process.
01:14:10Definitely the pace of the research and the need for research is a lot faster than our ability to get your timing from the government grant process.
Anna E. Diaz
01:14:21That’s right, make sense. Dr. Saphire, thank you so much for the time you took today. This is the second webinar we’ve had together and we learned so much.
01:14:31We’re obviously now entering this different chapter and the coronavirus story, getting that education is tremendous. Thank you as well to you and your team all the incredible work you’re doing.
01:14:41We want to thank our guests. It was wonderful to have you all join. We hope that you found this helpful. Many of you submitted fantastic questions. We hope we got a lot of them answered in the session.
01:14:50And thanks again Dr. Saphire for the time you spent with us.
01:14:52For those that we did not get to answer your question, we do commit to follow up with you and get them answered in combination with the La Jolla Institute and our team. So we’ll make sure to follow up with you directly.
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01:15:10And just so you know, we will have a recording of this webinar available in about a week on our website, which will distribute out. Thanks to everyone for joining, stay healthy, and be well. Take care.