Kai McKinstry, PhD, Burnett School of Biomedical Sciences, UCF talks about a universal flu vaccine.
So let’s start by asking you about your interest in a universal flu vaccine. Obviously your background is in immunology, a lot of different diseases you could look at. Why the flu in particular?
Dr. Mckinstry: Well, flu I got interested in flu number one, it represents a terminus threat to human health because of the possibility for pandemics like in nineteen eighteen, which was now a hundred years ago that caused millions of deaths worldwide. Secondly, it presents a pathogen, for an immunologist that’s really interesting because the immune system throws everything it has at it to try to combat it. And therefore we need to be aware of all facets of immunity and that makes it both really challenging in terms of understanding the virus and the immune response against it. It is really rewarding in that I hope we can really help improve human health.
Describe what it is that you’re looking at in the lab?
Dr. Mckinstry: So what we’re looking at in the lab is the immune response to influenza. We’re interested number one in what kind of an immune response is required to clear the pathogen. And then we’re really interested and focused on understanding how immunological memory is formed following the resolution of infection. And we want to do that because we ultimately want to figure out the signals that are important and establishing protective memory and that we can translate that then into vaccine strategy.
When you talk about memory could you describe what that is?
Dr. Mckinstry: So memory is really a defining hallmark of the immune system. And that means that once you come in to contact with the pathogen one time and gotten sick from it, the next time you are able to clear that infection much quicker and suffer many fewer consequences of disease.
So essentially you and your fellow researchers would be looking at something that would boost that memory or turn that memory on?
Dr. Mckinstry: That’s correct. Yeah, we want to boost that memory. We want to turn it on and we also want to make it as effective as possible. And that means priming the right kinds of cells and we are also interested in trying to get them to be at the proper locations which is equally I think important as to priming up large numbers of them. They’ve got to be at the right place.
Talk to me a little bit about how you’re doing that? And I know that might be a little challenging in layman’s terms, but just describe to me your research.
Dr. Mckinstry: Yeah, so the way that we do it is we have models in which we can track T cells and other cells that are specific for the virus and infected animals so we can track those cells. We can identify them and then we can isolate them out of infected animals and we can interrogate the function of the cells important proteins that those cells express might be critical in letting them reside in the right place. And we can start comparing different strategies of immunizing mice and look at the different ways in which these cells are similar and different in those different situations. So it’s really critical for us to use in vivo models because of course we’re interested in understanding how the cells, say for example, in the lung, where we want them to be are different from one’s in the spleen. This is very difficult to do with humans in clinical trials because it’s very difficult to get samples from other than in the circulating blood. So another focus of our research is what can we learn by looking at the cells in the spleen and the blood and the lung? Can we sort of figure out better ways to judge the efficacy of vaccines in clinical trials. So that’s all very complicated, but that’s sort of what we do. So we are very interested in understanding how the T cells responses are different in different organs and in different compartments of the body. So that we can understand what it takes to make the ones in the lung be better or the ones in the spleen be better and then hopefully translate that to human studies.
I know that one of the things that you had mentioned is that flu is a challenge because it’s a virus that is constantly changing.
Dr. Mckinstry: Right.
And I know our viewers have heard of all the different strains and I was immunized with this but it’s not going to work this year. How would a universal flu vaccine address that challenge of a strain that is constantly changing?
Dr. Mckinstry: Right. Well that is probably the biggest hurdle for our current vaccine strategy- is that in order to allow time to manufacture a sufficient version of the vaccine -people need to make guesses as to which strains will be circulating several months in advance. And when those guesses are off, that’s when the vaccine begins to help reduce efficacy. So our approach is to harness the protective potential of T cells which are a component of the immune system that is able to recognize the virus once it’s inside infected cells and thereby destroy the factories of viral replication. The great thing about T cell immunity is that it can recognize conserved parts of viruses across many different strains. So that this need to predict is lessened or eliminated. And that means that hopefully we can start working towards a once in a lifetime vaccine.
What is the benefit for a one time vaccine that protects you against all of these strains?
Dr. Mckinstry: Yeah, well the benefit would be first and foremost that we would not have to worry about the possibility of pandemics. And this is really the-crux of the detrimental possibilities that flu presents. The seasonal infections are bad, but the pandemics have the possibility of sort of crumbling our whole society, right. And so a once in a lifetime vaccine, number one is going to lead to far more people taking it. And therefore we will benefit because of greater compliance with vaccination. And second, it should protect us season after season, irrespective of what kinds of viruses happen to be floating around.
I want to ask a couple more questions that I had asked you before, and you are how many steps or how far away from this being able to move in to a production and get it out to the masses?
Dr. Mckinstry: Yeah, were at least I think a couple of steps removed from actual manufacture. And that’s because we as a field still don’t have a great handle on the signals that required to efficiently prime the most protective kinds of T cells. And that’s what we’re working on in our lab is understanding the critical signals to prime the effective T cells. Once we know those signals we can start testing vaccine strategies. And once we’ve got a vaccine strategy that works we can move to human trial.
I’m going to ask you the question that every great researcher hates and reporter will ask, and it’s the time frame question?
Dr. Mckinstry: Yeah.
Could we see it in three years, five years, ten years?
Dr. Mckinstry: Yeah, I think a safe estimate is ten years. I think that it’s just not something that’s ready to go on the shelf anytime soon and that’s because there’s a lot of complexity involved. Also, a lot of breaking down resistance against decades of vaccine research that’s led us to where our current vaccine is with the seasonal manufacture and the seasonal prediction. It will take time not only for us and others to figure out the new signals that are required, but also to make it more socially acceptable.
One question and you may not tell because it’s too early, but a method of delivery, like through the nose?
Dr. McKinstry: Right, well the latest –- yeah, the latest advancements in the field sort of suggests that the really important immunity is at the site of infection and for influenza the site of infection is the lung. And so it would make sense to think of vaccine strategies that target the lung so a nasal spray would make a lot of sense in terms of priming the area that’s actually going to be infected to provide immunity.
I’m going to ask you again in terms of vaccine delivery?
Dr. Mckinstry: Right. So it makes sense for a virus that infects the respiratory system to target vaccine delivery to the actual lungs and airways. So a nasal spray makes a lot of sense uh- but something to prime the area that’s ultimately going to be susceptible to infection, rather than the systemic approach, which is our current situation.
But could the flu mist style of delivery make sense too?
Dr. Mckinstry: Right, I mean in our lab we’re looking at resident memory cells that reside at sites of infection and it’s very difficult to prime those with a systemic approach, like a shot in the arm.
Last question is there anything I didn’t ask you that you that you wanted to include?
Dr. Mckinstry: I think the important things are what people are now finding is the route of immunization is really important in terms of generating the cells where you want them. So people have come to understand that location is as important as numbers. It used to be people just thought if we could make tons of memory cells we will be protected. But now we know that we can’t just make tons of them. We need to make the right ones at the right place. And so we also know that the cells that are responding to virus are different, and specialized at different sites. So you have the ones in the lung that are going to respond and do a lot of antiviral things. You have ones in the spleen that are going to respond and they’re going to act as helpers to help other cell populations. So this also makes it really tough to analyze in human studies what’s going on in the blood because we kind of have a mishmash of cells on their way to places. And we know from some of our studies in animal models that we have really specialized populations in the lung versus the spleen versus the lymph nodes. And so are challenge is to think of the vaccine that’s able to replicate those specialized populations. So we have the right cells doing the right things at the right place at the right time and that’s the real challenge with immunization. We want to sort of replicate what the pathogen does and get the benefits of this pathogen exposure without feeling sick. And how do we do that? So that’s our sort of challenge, yeah.
Okay perfect.
END OF INTERVIEW
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