Mark Moran [00:00:04] Hello and welcome to TGen Talks. I'm Mark Moran. The biomedical research community has responded to COVID-19 with speed and a sense of urgency. And while a priority remains on testing and treatment, numerous scientific questions remain unanswered. When it comes to this worldwide disease, hoping to answer one of those questions is today's guest, Dr. John Alton, an assistant professor in TGen's Pathogen and Microbiome Division. Dr. Altin's research interests lie at the intersection of immunology and genomics, where he studies, among other things, the body's immune response to viruses such as SARS-COV-2 to which causes COVID-19. Dr. Altin recently launched a study to investigate the antibody response in individuals who've been diagnosed with COVID-19, and recovered, hoping to develop new tools and treatments for reliably invoking a successful immune response against future outbreaks. Dr. Altin, welcome. Thanks for being here.
Dr. John Altin [00:01:06] Thanks, Mark. It's a pleasure.
Mark Moran [00:01:07] Immune response and antibodies as therapeutics sound interesting. What exactly are you looking for?
Dr. John Altin [00:01:13] Well, our lab is an immunology lab, and so we're really interested in the immune response and what it can teach us about how to fight this virus. You've probably seen there's a lot of interest at the national level on blood testing or serology where we measure antibodies against this virus. There are a number of reasons for doing that. These can be used diagnostically. They can also be used to understand how this virus has spread in the population, who has seen it in the past. There's also a lot of interest right now in using antibodies as therapeutics. There's a number of ways you can do that. You can take a sample from somebody who has been ill with the virus and then recovered and use that transfer that plasma into someone who's sick. And there's some evidence that that may help. Of course, the big the end game here, the longer-term goal is the vaccine, which also aims to generate antibodies against this virus. So we're interested in studying the antibody response against the SARS-COV-2 virus, which causes the COVID-19 disease and seeing what secrets we can learn from that response.
Mark Moran [00:02:16] Does your study differ from other antibody studies around COVID-19 and if so, how?
Dr. John Altin [00:02:22] Our hope with the test is to classify people's antibody responses, learn what they may mean for different people, whether they're protected, less protected. Anybody testing for COVID-19 is an urgent national priority right now. It's being talked about in these daily press briefings at the national level, and it seems like every day a new test is coming out of some type or other. I think what differentiates our approach is that overwhelmingly these approaches that are out there analyze this response. What I would call a global level. They take one big piece of the virus, one protein on the surface, and use that to detect antibodies against the virus.
Dr. John Altin [00:03:02] In contrast, the approach we're taking is what I would call a high-resolution approach. We're taking fragments of the virus, thousands of fragments that we generate in the lab from all across different pieces of the virus, across all of its genome, and we are surveying the antibody response across that landscape at high resolution. There are disadvantages and advantages of that approach. But one key advantage is the possibility that we may resolve different signatures of antibody reactivity against this virus. A lot remains to be seen.
Mark Moran [00:03:34] We know testing is used to confirm diagnosis, but is there additional information we can learn that might help us prevent others from contracting the disease?
Dr. John Altin [00:03:44] One of the benefits of having a good testing system is that you can identify who is currently sick, but also who has been sick. The blood tests that we're working on have the potential to reveal who has seen the virus in the past. Now, there's a good chance we don't know for sure, but there's a pretty good chance that those people have some level of protection against the virus. And so if we can identify those people, for example, if they're frontline health care workers and we have the confidence with the right data in hand to send those people back to work, we can get people moving again, get the economy moving and do that in a safe way. That's one of the things that this sort of testing can help with. Another aspect that may prove useful is that these tests can characterize the blood samples of people who have recovered from the virus and then determine which of those could be useful as therapeutics. Basically a type of blood donation, a plasma donation, where a sick person, a person who was sick, gives that material to someone who is currently sick. And again, the antibody testing can help to drive and inform that process.
Mark Moran [00:04:54] COVID-19, it's fair to say, has created a global anxiousness, in part due to a lack of a complete understanding of the disease. There remains a lot of unknowns that data will help answer. You've launched a study you hope provides data that might help put folks at ease. Talk about that.
Dr. John Altin [00:05:10] The study we're launching is called The COVID Immunity Study. The goal here is to recruit individuals from the public who have been confirmed, diagnosed with this disease positive and then recovered. And we're going to look at have blood samples that they send us using this low technology, but very flexible approach, where people put a drop of blood on a piece of filter paper, a blood spot is what we call that. And they send it into us. And then we do analysis on that spot to see what antibody responses those people have generated. So we see that as the first step in trying to develop tools for understanding the response for diagnostics and for understanding what type of an immune response may be protective, which could have all sorts of implications in the future.
Dr. John Altin [00:05:53] It's fascinating that you can gain that type of information from a few drops of blood. Is this test solely for COVID or will you be able to apply your findings to other types of viruses and outbreaks?
Dr. John Altin [00:06:05] Our initial focus is COVID-19, obviously, but we think that there's some reach here that could go beyond the current pandemic. And in particular, coronavirus is actually a large family of viruses. It's not just this current virus that we'll hear about. There are a number of current viruses that circulate every year and there are coronaviruses that live in other animals that have the potential just like this one did, to spread across to humans and cause serious global problems of the pandemic scale. And so one of the things that we look at when we analyze these blood samples is reactivity, not just to the current coronavirus and all of its elements, but also to some of these other coronavirus family members to understand where they are in the population and maybe to predict what the next dangerous one could be.
Mark Moran [00:06:52] Keeping it simple, what is it exactly that you're looking for in those few drops of blood?
Dr. John Altin [00:06:58] What everybody in this field hopes right now is that the immune response to this virus is protective. And so there'll be some indication of that in the coming months. Whether someone who has had the virus generated a response is protected from disease. In this study, in particular, what we hope to find are signatures, antibodies signatures, of exposure that are clear and robust and perhaps even signatures that differentiate the different types of disease that people experience. In some ways, the Holy Grail would be signatures that tell you what type of immune response protects versus the type of immune response that doesn't protect. And that could be useful for those developing vaccines and also for those who are involved in this plasma therapy, where they're taking plasma products from people who have recovered and using them to transfer into people who are sick with the disease.
Mark Moran [00:07:47] Why is it important that participants have been diagnosed with and recovered from COVID-19?
Dr. John Altin [00:07:52] The reason you need to have had the virus for these types of studies is that by having the virus, you generate an immune response. And unlike the nasal swabs that you may have heard of, which can detect the virus in its early stages, the immune response take some time, often a week or two to generate, and then it gets stronger with time. So by waiting that that initial period, we give them the body's defenses, a chance to build up that immunity so that we can detect it robustly.
Mark Moran [00:08:20] If genomics has taught us anything, it's that we are all unique thanks to our DNA. If that's the case, does this mean our immune systems are unique as well? And if so, can we apply the answers you find broadly across populations?
Dr. John Altin [00:08:34] One of the hypotheses that's out there is that the reason some people get really sick from this disease and others barely even notice they have it is that there may be differences in their immune response in the existing immunity that they have. Coronavirus is one member of a family of viruses and we see these other family members very frequently. And it's possible that there's something about the immune response to these other viruses that we've all seen many times and that don't usually cause severe disease. There's something about that immune response that may affect the way we respond to this new virus. That's one of the things that we're interested in pursuing and understanding.
Mark Moran [00:09:10] There's a lot of talk right now about the need for a vaccine. Will your immune response study contribute to that process?
Dr. John Altin [00:09:17] We're not directly involved in developing a vaccine, but I think there's potential for understanding the immune signatures in the way that we are planning that may feed into vaccine development. In particular, one of the concerns with this virus is that there can be good antibodies and perhaps they can also be bad antibodies that exacerbate disease. And by defining the antibody response in this very careful and sort of deep way, it's possible that we can distinguish those types of responses from each other and guide the vaccinologist as they choose which targets and strategies for vaccination.
Mark Moran [00:09:49] Who can be a part of the study and what will they need to do?
Dr. John Altin [00:09:52] We're accepting people nationwide. The criteria are 18 years or older. U.S. resident and confirmed tested positive with just this disease and then recovered. So we've developed a system where we send participants a kit that they can use. This kit contains everything that you need to collect a sample. This contains a little piece of filter paper as well as a lansit that you can use to poke your fingertip and draw out a drop of blood. We also have an app, a website and an app where participants, once they receive this kit, are guided through the steps. They need to collect a sample and we use that as a tracking system. Once we receive those samples back, we punch out using essentially a hole punch. That piece of blood on the card put it into a little tube containing liquid and recyclables. It basically recreating the blood sample that came out of the finger then we use that to do our analysis.
Mark Moran [00:10:48] COVID-19 and immune response. Fascinating stuff. Dr. John Altin, thank you for your time today and your important work.
Dr. John Altin [00:10:54] Thanks, Mark. It's a pleasure. Stay safe everyone.
Mark Moran [00:10:57] Dr. John Altin is an assistant professor at TGen North's Pathogen and Microbiome Division in Flagstaff, Arizona. For more episodes of TGen Talks, visit TGen.org/TGenTalks TGen is an affiliate of City of Hope. Thanks for listening. I'm Mark Moran.
