COVID-19 Boosters Increase Protection with Alexis Demonbreun, PhD

Erin Spain, MS: This is Breakthroughs. A podcast from Northwestern University Feinberg School of Medicine. I'm Erin Spain, host of the show. In recent weeks, with the emergence of the omicron variant, the CDC's guidance on who should get COVID-19 boosters changed quickly from just select groups to now everyone over the age of 16. But what do we know about the effectiveness of COVID-19 boosters and how might boosters better protect us from new variants such as omicron? Here with insight is Alexis Demonbruen, assistant professor of pharmacology at Feinberg, and the author of a new study that found COVID-19 boosters seem to supercharge antibody response. Welcome to the show.
 
Alexis Demonbreun, PhD: Hi Erin, thank you so much for having me today.
 
Erin Spain, MS: The study about boosters that we're going to talk about today, comes from a subset of participants and a Northwestern project called the SCAN Study. Now, Dr. Beth McNally has been on past episodes talking about this study, but give me a refresher on SCAN and how this study has evolved from early 2020 to today.
 
Alexis Demonbreun, PhD: Basically, back in March, when the pandemic was just starting, we teamed up with Thomas McDade, Brian Mustanski and Rich D'Aquila to get SCAN started. And so basically what we did was we wanted to look and see what the seroprevalence of COVID was in Chicago. So, at the time COVID just came around, it was really hard to get testing and a lot of the medical providers actually were suggesting if you were not severely infected to just stay home and quarantine. And so, the numbers that we were seeing from the clinical testing we assumed was actually much lower than the actual incidence in the community. And so, what we did was we actually developed an assay in the lab to actually quantify the antibodies, the IgG antibodies against COVID-19 as a measure to look at the number of people that were infected in Chicago. And so basically, our unique take was that we actually were able to do all of this without contact. And so, we actually would mail participants kits so that they could sample their blood in the safety of their own home and not have to come out to the hospital to get a blood draw, which is normally like the standard way you do serology testing. And they were actually able to just mail us their blood samples back. And right in the lab, we were able to analyze the samples and look for these IgG antibodies against COVID. And what we found originally was 18 percent of Chicagoans actually were exposed to COVID, while the clinical diagnostics was only showing around two and a half percent. There was a sevenfold increase in those Chicagoans that were infected. COVID continued. We knew vaccines were eventually going to be coming, and we wanted to use this platform to watch that the antibody levels over time and then eventually evaluate the response to these vaccines. And now here boosters.
 
Erin Spain, MS: On November 21st, your team published preliminary findings from a small group in the SCAN study that had received boosters, and you showed that these boosted individuals had supercharged antibody response. Tell me about this study and the findings.
 
Alexis Demonbreun, PhD: Over the last 18 months, we've had over ten thousand people join SCAN and participate, giving us free samples, and we ended up having these 33 participants qualified for boosters early on, receiving their boosters in September and October of this year. Since we had their previous vaccination samples, we were able to compare their levels from receiving dose two boosters waning over time to immediately before receiving the booster and then seven days after their booster. And what we found was, on average, the participants antibody levels increased 25 times higher with a booster vaccine than the levels they had just the day before. And what was shocking to us was that these booster levels were actually four times higher than their maximum amount of antibodies they received after their second dose of vaccine. So that's why we're saying these are supercharged. Getting that extra boost is giving you an extra, well, as you say, boosts in your antibody levels. And so, we were super pleased to see that high of a response in our population.
 
Erin Spain, MS: Were you surprised by these findings?
 
Alexis Demonbreun, PhD: We definitely know boosters work, so we were anticipating we would see increase in antibody levels over time, as this is very reminiscent of our previous data, where we had seen people who had natural infection of COVID-19 had a more robust response to their dose one and dose two vaccinations, which was equivalent to us receiving those who didn't have COVID, a third dose, right? So, we are anticipating that. Yes, we would see a robust response. But a 25-fold increase was just absolutely astounding. We were just anticipating that this third exposure would elicit a response much quicker. And so, we looked at seven days, but guessing if we were to look at 21 days, this might even be higher than 25 times.
 
Erin Spain, MS: Do the findings suggest the booster attacks for a longer duration than the two-dose regimen alone?
 
Alexis Demonbreun, PhD: That's what we're anticipating. We all know that the antibodies have waned over time, and there's a standard half-life to antibodies. And so, what we're expecting is since these antibodies are starting at a much, much higher level, that it's going to take them longer to decline, giving us more protection.
 
Erin Spain, MS: What did you see in the SCAN study? How much did the antibodies wane?
 
Alexis Demonbreun, PhD: Actually, very similar to what the manufacturers are reporting. We are kind of seeing a half-life of around 30 to 40 days starting out really high when, you know, depending on what variant, still gave us a lot of protection. But we're looking to see with these boosters if the half-life is going to be similar or not, and that's going to be determined in the near future.
 
Erin Spain, MS: We're hearing a lot about omicron and how it seems harder for the vaccine to neutralize this variant versus other variants. Explain what we know about omicron, and do you think boosters will provide enough antibody response to fight it off?
 
Alexis Demonbreun, PhD: We know omicron has a number of variants, actually a large number of variants, both in the receptor binding domain, which is the area that the antibodies are targeting to try to block the virus from entering the cell, as well as variants outside of that region. And so similar to delta, we know that having a large amount of antibodies, although they weren't designed necessarily to these variants, having more of them was sufficient to actually to protect against the variants in our preliminary data and similar to what Pfizer has just released, they are showing that yes, having this robust response after the booster vaccination that elicits this huge increase in antibodies was giving us protection against omicron, even though those antibodies weren't designed specifically to that variant.
 
Erin Spain, MS: What has the reaction been in the scientific community, in the media, to this study, the small study that you just put out a few weeks ago?
 
Alexis Demonbreun, PhD: Actually, we're having a lot of positive feedback and we're hoping to get it published in a peer-reviewed journal. But most importantly is we have had a lot of media attention, Twitter retweets, news, attention, newspapers writing about it, getting it out to the public, and that's exactly what we want at this time. We want to show the public that these boosters are working. We have faith in them, our testing, that has nothing to do with the manufacturers, are showing similar results and that we need them. Go out and get a booster.
 
Erin Spain, MS: Well, there's good news, according to the White House COVID-19 response team, vaccinations have surged with about 12.5 million shots administered over the last week, including seven million booster shots. Do you plan to do a study on a larger sample of booster participants now that boosters are more common?
 
Alexis Demonbreun, PhD: We're definitely hoping to expand beyond our smaller 33-person study. We have many people already enrolled that we have their pre-serology on, as well as their responses after dose one and dose two. And so, we're hoping to actually be able to look at the booster response over time to calculate out like how long we expect these antibodies to last and when we might anticipate needing another booster, if we need another booster, which you know, we're hopeful, but it's probably coming down the pipeline. We're very excited to expand our work and continuing studying these vaccine responses.
 
Erin Spain, MS: I want to touch on another study that you published in September and the Journal of Infectious Diseases. Your team investigated whether the antibody response to COVID-19 mRNA vaccine is similar in men and women. What did you find?
 
Alexis Demonbreun, PhD: In that study we evaluated the antibody response in men compared to women, as you said, and originally just looking through the database that you know, the app that you are asked to join when you get vaccinated. Women were reporting much more symptoms after vaccines than men. And so, we questioned whether there were symptoms correlated with a more robust response. And with other vaccine,  this has been seen that women do have a higher immune response against vaccination. And so, when we looked after dose one as well as dose two, we did, in fact see there was a significant increase in antibody levels in women compared to men. We are looking to kind of continue on and see if that has anything to do with breakthrough infections or longevity of these antibody responses and then additionally doing the same thing with our boosters now.
 
Erin Spain, MS: Now what is it about women that makes this response stronger?
 
Alexis Demonbreun, PhD: A lot of the immune genes are on the X chromosome, and since women have two, we actually can mount a higher response.
 
Erin Spain, MS: Before SARS-CoV-2, you spent a lot of time working on muscular dystrophy. Tell me about that research. How you been able to continue it? And have you been able to link the COVID-19 research with your muscular dystrophy research?
 
Alexis Demonbreun, PhD: Pre-covid I definitely had a scientific focus on muscular dystrophy looking at muscle regeneration and injury repair. In regards to COVID, what we actually did was, we enrolled about 15 neuromuscular patients into SCAN. And the reason behind this was many patients that have neuromuscular disease are on chronic immunosuppressives. And it's known that obviously immunosuppressive can reduce your response to vaccination. And so, we wanted to use our quantitative assay and see how well this population would respond to COVID vaccines. And importantly, we found that all of the participants really did have a great response, much higher than even after COVID natural infection. That was super exciting to us that we didn't really see this huge decrease in antibody levels if you were taking steroids suggesting that this population should actually still go out and get their vaccines, get their boosters, and it'll help protect them.
 
Erin Spain, MS: Is there hesitancy in that group?
 
Alexis Demonbreun, PhD: People are afraid that the vaccination could exacerbate their symptoms or if they're already having a lot of these severe muscle atrophy and aches, how is the vaccine gonna do any good? Is it going to do any good for them or is it going to make their disease worse? And although our study was really small, we really didn't see any adverse events or people complaining worse than the normal, the healthy population on their symptom severity or how long they lasted. So that was a very big positive.
 
Erin Spain, MS: I want to talk a little bit more about the SCAN study. What has it been like to be part of such a big and unique project that really is a truly Northwestern project, everyone involved? Just give me your take on what the experience has been like.
 
Alexis Demonbreun, PhD: It's been absolutely wonderful and eye-opening. I've never been involved in such a wide, community-based study before. Hooking up with Thomas McDade and Brian Muskanski and Richard D'Aquilla and of course, Beth in the Center for Genetic Medicine, taking all our different expertise coming from basic biology to anthropology to public health and mixing all of our expertise, I think is really given us the success that we've had in this project and really allowed us to make a big impact and understanding the antibody response. It was just really great to see how many people in the community actually wanted to participate and were excited to participate and really wanted to be informed about what's going on. Originally, we had almost like 40,000 people request to be enrolled, and so based on all of our criteria, we actually were able to enroll near 10,000. So, we know Chicago's very heterogeneous. And so, with SCAN, we definitely try to get a good representation of what Chicago looks like with different ethnicities, genders, age, basically just representing all of Chicago. And shockingly, we actually were able to meet that goal, and we did enroll a very diverse population, making our study really important for our population.
 
Erin Spain, MS: This could be used as a model in the future as a way to bring more people into clinical trials and studies because it didn't require them to come. Do you see the dried blood spot becoming a popular way to gather information?
 
Alexis Demonbreun, PhD: I absolutely do. It's used a lot in the anthropology field and obviously is used a lot in the pediatric area. But I think in our world moving forward, having a way to get samples back and forth without requiring people to come to the clinic, putting that extra burden on the health care system and even on the participants themselves. You know, a lot of older people might not be able to have the means to get places. This is just a very convenient way to do a true population-based, not subject ourselves to who might be able to get to a hospital or be near a hospital. I mean, you can mail things just about anywhere these days. And so, yes, I really do think that this is going to be really important moving forward.
 
Erin Spain, MS: Well, thank you so much for coming on the show, explaining this latest research and sharing some of the other work that you've been up to.
 
Alexis Demonbreun, PhD: Yes, thank you so much for having me, and I hope we can chat again is as we acquire more information and data over the next couple of months.
 
Erin Spain, MS: Thanks for listening! Be sure to follow us on Apple Podcasts or wherever you listen to podcasts. And if you're a member of the medical community, you can claim CME credit for listening to this podcast. Go to our website feinberg.northwestern.edu and search CME.