One small company is trying to change the way we vaccinate against influenza. Longhorn Vaccines and Diagnostics, which made its name during COVID-19, is working on a universal flu vaccine that will kill the virus at every stage of its growth.
Most flu vaccines focus on preventing the virus from entering cells, but that doesn’t completely stop it from replicating and infecting. Longhorn is taking a different approach by targeting flu from getting into cells, but also replicating and getting out of cells. Their vaccine candidate, LHNVD-105, also pushes the body’s immune system to kill the virus, not giving the flu a chance to rest.
DocWire News spoke with Longhorn’s Co-Founder and President Jeff Fischer on the mechanics of how how their vaccine candidate works.
DocWire News: Please give some background on yourself.
Jeff Fischer: I started my career as an infantry officer in the United States Marine Corps. I did four years kind of in between a lot of the conflict and went back, got an MBA from the University of Texas at Austin and was asked to come and join the family business, which was biotech, something I thought I would never do, and started working with my father on building a new company out of one that he had previously been involved in forming to develop monoclonal antibodies for preventing bacterial infections in premature babies, which was where he got his start.
He and some colleagues had discovered that antibodies could prevent RSV infection in premature babies, and that work led to them starting a company, licensing that technology to MedImmune, which became division of AstraZeneca. To date, not for much longer, but to date is still the only product that’s ever been licensed for prevention of RSV infection. That kind of got the family kicked off in the business and has been doing it ever since. I joined in 1998, we had a very successful company that used standard venture funding to build, and we went into phase two with several products, including a monoclonal antibody for preventing staphylococcal infections. We ended up selling that company in 2005 to a hedge fund and then started Longhorn Vaccines and Diagnostics.
Talk to us about Longhorn Vaccines and Diagnostics. Specifically, how is the company changing flu vaccinations?
We started back in 2006, spinning out the Vaccine and diagnostics group. We were looking for products that would impact an influence of pandemic, and we saw that H5N1 influenza virus was circulating in Asia, it was mostly in poultry, but when it did get out into humans, it had a very high mortality, 40 to 50% of people who got H5N1. We were looking for approach where we could not just impact H5N1, but really any influenza strain that might come up because generally these strains change quickly and that’s when you get a pandemic strain. We were looking for an approach which would be universal and so we’ve spent the last 17 years looking for a way to attack a virus that’s very good at mutating and very good at escaping from really any approach.
We are changing it by not going after an individual component of the virus. We’re trying to attack the virus from multiple directions and put stress and pressure on it at every stage of its growth. We’re going after not just the standard targets like hemagglutinin, but we go after hemagglutinin, neuraminidase and the M2E matrix. We are going after the virus as it tries to bind the cell to get into the cell. Once it gets into the cell, we go after it while it’s trying to replicate. A lot of targets, once it gets into the cell, it has kind of freedom to replicate. We’re also going after the neuraminidase, which is how it gets out of the cell. We’re trying to keep it from getting into the cell, attack it while it’s trying to replicate and then try and attack it while it’s trying to get out of the cell.
What we’ve been able to do is build a multi-component vaccine using a composite peptide approach, and then on top of that, adjuvant it so that you get a further response as well as bringing in T-cells and other components to get the whole body to really be a part of attacking the virus. We’re taking what we believe is the most comprehensive approach that anybody will have taken into the clinic to go after influenza, and we think that without taking this comprehensive approach, the virus just gets a chance to mutate.
What are some weaknesses of current flu vaccines that Longhorn improves on?
I think that there’s two weaknesses. One, the current flu vaccines chase the virus. They look for what is currently circulating and they try and match up to what’s currently circulating. What we’ve seen from flu over decades is that the flu’s always changing and so by the time you create the vaccine as to what viruses are circulating at the manufacturing time, those are already changing and they’re already different. Even if they’re minor differences, it allows it often to escape. I think that the biggest challenge is that they’re just not well-matched by the time the virus really starts to spread in the community. I think that’s one of the big challenges. The other is that these vaccines really don’t last very long. We have to time when to get them. I’m a big believer in flu vaccines. I get the flu vaccine every year.
I try and figure out whether I want to get it in late October, early November. I’m trying to figure out when the season’s going to start so that I have maximum protection because I know that it probably has probably a 12 week really good chance of working, and that’s if it’s well-matched. So durability, I think is another key component of this. I think the weaknesses are that they chase the virus and that they’re not very durable, and we’re trying to go after both of those. We’re looking to try and have a vaccine much more similar to a Shingrix, which provides great protection and five to 10 year protection. That’s what we really think is going to be the benefit of our vaccine, is to really provide a product that people believe in and are willing to get.
I think that one of the things that’s come out of the Coronavirus Pandemic is that people are just not necessarily sure they want to get a vaccine every six months or four months or three months, and then when they do get a vaccine, they actually expect that they’re not going to get sick. I think that that’s been one of the challenges with even those people who truly believe in vaccines are getting a little bit of fatigue and feeling like they’re getting something that’s not actually helping them. Yes, the feeling is that you’re staying out of the hospital, that maybe you’re not dying. But for the healthy population, I think that they’re starting to be a little skeptical of vaccines that don’t keep them from getting sick.
Talk to us about Longhorn’s partnership with the U.S. Army to develop your LHNVD-105 flu vaccine, and its possible impact.
We’ve had a long relationship with the US Army. My father was a Army physician for 23 years, was a professor at the military medical school, worked very closely with the Walter Reed Army Institute of Research, and so had very close relationships with the team over there, especially the adjuvant team. The US Army’s adjuvanting group is one of the world’s experts in building adjuvants and so the adjuvant that is in Shingrix, GlaxoSmithKline’s shingles vaccine, was licensed out of that US Army adjuvant group. They’ve come up with one that that’s has many of the same characteristics of the GSK adjuvant, but is even better at reducing some of the effects of vaccination. I’ve had the Shingrix vaccine, two doses. Each one of them I got pretty sick after the dose and so their new formulation does all of the great things that the adjuvant does while minimizing some of those effects of the vaccination.
We’re very excited about it and one of the things about peptide vaccines is they really need good adjuvants. In this case, we’re working with what we believe is the next generation best adjuvant in class. Because this flu is of great interest to the US Army, we’re also working with them to get through using their facilities, their clinical trial facilities for phase one.
What are some key takeaways you would like to leave our audience with today?
I think that one of the things that we’re excited about is that the composite peptide approach was not something that we started with. It was something that we generated because we knew that to go after a virus that’s as challenging as flu, we needed an approach where we could attack it from so many different angles. What we now have is not just a great universal flu vaccine, but we have a platform that really will allow us to go after some really of the most challenging pathogens and combinations of pathogens and be able to provide vaccines that last for a long period of time and not something you just need to get every year.
One of the other areas we’re working with US Army on is a broad sepsis vaccine, being able to pull together multiple bacterial components and be able to provide protection against a wide variety of bacteria and the toxins that are released by them, which is something that is very important to the military for preventing battlefield infections. We’re excited about this universal influenza vaccine. We think it’s going to be best in class, but we also have a really nice pipeline behind it of great products that can deal with a lot of very challenging diseases because of the platform that we’ve built for it.
