We sat down with Dr. Robert Carnahan from the Vanderbilt Vaccine Center to talk about antibody therapeutics and how they can be used in the fight against COVID-19.
"Antibodies discovered at Vanderbilt for prevention of COVID-19 granted FDA emergency use authorization" - VUMC Reporter
Video Transcript:
The larger health impact is just giving us again one more tool to treat people. We have a vaccine for people who have fully functional immune systems, and we highly advocate that people get those vaccines. They're safe and effective but that doesn't cover the full population. We have a lot of people out there who aren't able to respond and this gives a tool for them. We can cover them and protect them in a way that we're not able to protect them right now and do it in a way that's convenient and is going to help it go into full usage.
In response to a virus, people make all kinds of different antibodies and those antibodies function in different ways. Some of those antibodies are helpful and protective, some of them are not so helpful and protective. Your body is conducting all these little experiments, developing antibodies, but when we collect a whole b-cell sort of collection from a donor, we have to sort through all of that. We get the whole collection. We're looking for those that recognize the virus, so they're specific to the virus, and then we start to sort through those to see which ones are the most functional ones that neutralize or block the virus in some way.
[Q: How did you pick the best antibodies to SARS-CoV-2?]
That was quite an effort right? So when we started getting b cells from human donors, we had well over a hundred thousand b cells that we were looking through. We got the genetic code, the DNA code, to make all those antibodies and then used computer algorithms and bioinformatics to down select to about a thousand of those antibodies that we started to really dig into. All those thousands we started to make in the lab and sort through but we knew we wanted spike proteins. So everyone knows this protein now on the surface of SARS-CoV-2, so we're sure we wanted proteins that recognize spike. We were pretty sure that the best of those would be ones that recognized this little piece of spike called the RBD, that's the receptor binding domain. This is the part that you know sort of the end of the finger that literally reaches out and touches the human cell so sort of blocking the key that's trying to touch the lock. That’s where we focus most of our energy.
[Q: How does this combination deal with variants?]
Early on in the pandemic we also made this strategic decision - it's an RNA virus we know the RNA viruses have a propensity to change. We suspected that would happen and so we knew we wanted to go in with what we call a cocktail – which would be two antibodies to distinct sites. The idea being there if you have two antibodies that are at completely different sites, it's very unlikely a virus is going to be able to change two things at once so if it changes one, you have the other side and vice versa. So you're kind of preventing, you're mitigating any kind of escape risk. We're also doing basic science biochemistry experiments looking at this concept called synergy. Which is the idea - could one antibody not only function but could it be combined with another antibody and the sum of the two is greater than either of them individually. And that was a big stepping stone for us because we were very fortunate to find that we did have one. Within our 20, we found an antibody partnership where they not only worked well together, they worked as a good cocktail to prevent escape, but they were also synergistic so they would sort of be helping one another function better. Those were the two that actually ended up being the best.
[Q: What is the target population?]
You can think about that in different ways but if we want to prioritize, let's talk about how do we prioritize those populations. I mean in that when we were starting it we didn't actually know. We thought we had an inside track to vaccines but we didn't have a vaccine at the time. There's one thought was well - maybe the antibodies are the central sort of response, right? We didn't know so we had to make them as good as possible because we didn't know what other tools we'd have in the treatment toolbox but as time has gone on now we do have not only one but we're very fortunate to have multiple very effective vaccines which we would highly advocate people get. And in the presence of a highly effective vaccine then - what role do antibodies play? Well they still play a role because the vaccine response is dependent on the individual. If you get the vaccine, it's basically teaching your body how to respond to that virus. Some people's bodies either through something going on in their own body or maybe we're actively immunosuppressing them to help them in some other disease state. We're actually suppressing their immune system or they're immunocompromised, they just don't have the ability. In either case, they don't necessarily have the full sort of ability to respond to a vaccine. They might have a partial response. They might actually have almost no response and so in those cases, what we're looking for is antibodies which are the result of a successful response. We're basically cutting to the end of the line and now we're going to move those up and just give them, what's called passively, we're just going to immediately give them the solution. And that sounds really great, why don't we do that all the time? It is really great but vaccines can last months and years and also are really inexpensive. Antibodies tend to have more limited time frames. A standard antibody would just have a time frame of about a month or two and they also just cost more to make at this point. The target population are keeping it limited, the limited supplies and higher costs to those people who can't get vaccines, immunocompromised immunosuppressed people, who can't sort of mount what we think is an effective response to the vaccine.
[Q: How are these new antibody therapies delivered?]
Sort of the next wave of antibody therapies, including the one from AstraZeneca that we helped collaborate on which can be given fully just IM dose, in a single visit. IM dose - this is the kind of thing you would normally think about, just a standard shot into a muscle gives that 12 months of protection so that's what we're most excited about. It is not just that we're providing a solution that could be helpful to immunocompromise/immunosuppress people, but in a format, that's actually going to make it readily accessible to them. That could be given in a doctor's office that you don't have to go to a specialized center to be able to receive it.
