Louis Picker, MD, Associate Director, Vaccine and Gene Therapy Institute, Oregon Health & Science University, talks about the HIV virus.
Talk to me about this vaccine platform that you guys worked on. Can you tell me what it is and how it works?
PICKER: Yes, this was a vaccine concept that I thought about 20 years ago and actually came to OHSU to explore. It uses an ancient herpes family virus – not herpes itself, but a virus called cytomegalovirus, which has unique immunologic properties. It persists in our bodies at very low levels and generates very strong, very potent cellular immune responses. We thought that these potent responses could be harnessed to attack pathogens that conventional vaccines didn’t work on, in particular HIV.
How is this different than how vaccines are currently developed?
PICKER: It’s not that different in terms of how they’re currently developed. It’s just a completely different platform that generates unique immune responses that are very different from the platforms that are currently out there. It doesn’t focus on antibodies, which is what most vaccines do, instead it focuses on T cells and it generates T cells which are of high magnitude. That means there’s a high frequency of them that have a lot of what we call effector potency – that means they have strong antiviral activity. The key aspect is they’re located on all the right places to intercept the incoming pathogen, like HIV, right when it first gets into the body. It’s basically putting up a strong line of defense on the beachhead that would prevent the HIV infection from taking hold. It doesn’t prevent infection completely, but it basically stops it in its tracks. At least that’s what it has done in our monkey experiments.
Could you talk a little bit about the monkey experiments – your findings so far?
PICKER: We’ve been working, presenting and publishing monkey experiments for the last 10 years. The effectiveness of the vaccine has been very consistent. What happens is we challenge the monkeys with SIV, which is a very potent equivalent or similar virus as HIV but it works in monkeys rather than people. The animals get infected but immediately stop the virus – at least 50 to 60% of them will stop the infection and the infection actually goes away over time. So, it’s a unique pattern of effectiveness that no other vaccine has shown and it’s very consistent. A lot of our work now is trying to understand what the mechanisms are, what the features of the vaccine need to be in order to generate these effective responses so that we can translate this to humans.
You said that it worked 50 to 60% of the time. What are the other factors?
PICKER: There’s other factors that we’re on now that in terms of the ability of the monkey to respond with a certain kind of response. Some of them respond with the effective response, some of them do not. As I said, we’re working on ways to try and get more monkeys to respond with the effective response. In humans, it may be that all of them respond, you don’t know until you test it in humans. With monkeys, our best vaccines are about 60%.
The findings that you found in the primate study, when people do drug tests in animals, do those same findings typically translate the same effects in human trials?
PICKER: Yeah, often. I mean, the primates that we use here are the closest animal models to humans. They’re not humans, obviously, they’re a little different, and so that’s why we’re working so hard to make sure we understand how it works so we can translate that understanding, not just the vaccine itself, but that understanding to a human-adapted vaccine. For example, in COVID-19, all of the vaccines that are currently working that are out there, the efficacy was all predicted in monkey studies prior to the evidence in phase three clinical studies.
And right now, there’s a phase one trial going on in humans. I know you’re not part of it, but can you speak a little bit about that transition from the study in primates to now humans?
PICKER: The study is being conducted by Vir Biotechnology, which is a company that Klaus Frueh and I helped found a number of years ago. We’re not directly involved in it, but we’re advisors and we provide the insight to say, ‘this is what you should look for to see if it’s going to be effective’, ‘this is the design of the vaccine that we think would translate to humans’. They’re started with our vector number one. It’s called Vir- 1111. That trial is underway. It’s based on what we thought was the best design three or four years ago. We’ll see how well it works in the clinical trial. It might require tweaking to get it to work properly because, again, we think we know what we’re looking for in terms of the immune responses. Even in phase one, we can get a good idea of whether we’re getting what we think we need to get. If necessary, we will iterate the process and try a modified vector. Or maybe this one will work just as is. We will see. It may take one round or it may take a couple of rounds, but we’re pretty confident, based upon our monkey studies and our understanding of human CMV, that we will eventually be able to recapitulate what we see in monkeys in people.
This vaccine platform is currently being used to help develop the HIV vaccine. Are there any other typical diseases that this could potentially work for?
PICKER: This vaccine is designed, as sort of a special attack force that goes against pathogens that are normally able to evade the immune response. And the concept behind it is really quite simple. You have this big attack force that’s there all the time so when, the pathogen comes in, it attacks it right away before those pathogens can get tricky and use their various mechanisms of immune evasion. So, it’s an early intercept, get it before it unloads its weapon. It’s also in clinical development for tuberculosis, which is another immune-evasive pathogen that we’ve shown efficacy in monkeys. There’s promise that it could be used for cancer as well as other pathogens. With something like COVID-19, a simpler vaccine works, we wouldn’t use this more elaborate vaccine. This is really the special forces vaccine that allows us to go after pathogens which are not susceptible to antibody responses.
I think you mentioned before, it’s not really so much as a preventative vaccine, it’s more of catching it early before it spreads its damage, right?
PICKER: Well, it is a preventative vaccine. It prevents the disease; it prevents the overt infection. So, the infection that the animals get is not noticeable to them. They don’t get sick at all, very little SIV virus is produced. It effectively prevents the disease and the infection. It doesn’t completely prevent infection in that the virus still gets in there and stays for a while. But it effectively prevents the disease that occurs from the infection, so it is a preventative vaccine.
So, it’s something like the HPV vaccine – something similar to that effect.
PICKER: All vaccines are used to prevent disease. That’s their primary function. I mean, the measles vaccine doesn’t necessarily keep every measles virus out of you if you get exposed, it just prevents it from growing and expanding and causing measles disease. So, you could stop the incoming pathogen right up the mucosa so it never gets in at all. You can stop it a little bit further in, you can stop it after it spreads a little bit. As long as you stop it before it causes disease, that’s preventing the disease, and that’s the purpose of these vaccines.
It wouldn’t necessarily help people that currently have this disease?
PICKER: It’s more for preventing infection. We’re working on asking the question of whether it can be used as a therapeutic vaccine. So far, we haven’t got good evidence that it can work like that. Once the SIV infection is established, it’s a little more difficult to root out. We’re working on ways to see if we can make it work. But so far we don’t have any conclusive evidence that it will work in that setting.
What do you think this will mean for people that are worried of catching HIV? What impact do you think this will have on people?
PICKER: Well, I mean, if it goes through phase three clinical trials and shows to be effective, then it’ll be like any other vaccine. It will hopefully help stem the epidemic. It’s not just what the vaccine does for the individual person it’s what the vaccine does overall to the epidemic. If the epidemic goes down so that it’s no longer prevalent out there, then, people don’t need to worry about it anymore. It’s just like COVID vaccine. Just because you’re vaccinated, you wouldn’t go up to somebody who’s sick with COVID and stick your face in their face, right? It certainly gives you peace of mind that, if you’re just out in the world, that you’ll be protected from catching the disease, and that’s the same concept.
How did you get involved in this research?
PICKER: This was my idea.
What brought about the idea?
PICKER: I was actually in medical school when HIV first hit and it had a very lasting impact on me, taking care of those patients and studying HIV in the early ’80s. I became an immunologist and, working on immunology over the years, I worked with CMV, which is the virus we’re using as the vaccine, and our group was one of the first to really recognize how potent it was. I came here to work with Jay Nelson, who’s the head of the VGTI who’s a CMV expert to explore this concept. And lo and behold it worked. Certainly, in an experimental system it worked. So, we’ve been following it for 20 years now. It turns out that the responses that are listed are even more different than we thought at the beginning. It’s not just that they’re there at the start, they also have unique other characteristics which we’re defining. Which is different from all other vaccines. So, there’s been a lot of science involved in this – very interesting science. Not-previously-seen-before-type responses. We can adjust the genes of the vector and change – and dial those responses in, which is very unique to this vector. It’s been a fun scientific endeavor. And it continues to be fun. As we learn more and more, it’s getting more and more interesting. And we hope what we learn will translate to a clinically-useful vaccine.
Interview conducted by Ivanhoe Broadcast News.
END OF INTERVIEW
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