Please can you give a brief history of vaccination? Why have vaccines traditionally been given via needles?
Vaccination was started by a gentleman named Edward Jenner who, while dealing with young boys that milked cows, came to the conclusion that there must be a way of using cowpox to vaccinate children against smallpox. For some time, he researched cowpox, which is a milder disease than small pox. Eventually, he was able to show that by exposing children to the virus, they could become protected from smallpox.
He did that in the late 1700s and within a few years, hundreds of thousands of British people had been vaccinated in that way. That's how it started and everyone began to understand blood immunity and how to generate blood protection using vaccination by needle.
However, although they understood this systemic defense system, they were not so familiar with the mucosal defense system and they believed that the direct administration of vaccines into a muscle was one of the best ways of generating systemic antibodies.
Eventually, scientists became familiar with mucosal vaccines or nasal vaccines, which looked like a sensible way to go. However, it's more difficult to raise immune responses using those vaccines and the scientists turned to intramuscular vaccines or parenteral vaccines, which are mainly designed to raise systemic immune responses.
Now, however, there is a clearer understanding of the importance of the mucosal immune system and a renewed interest in the use of other administration routes.
What prompted Mucosis to start developing needle-free vaccines?
Firstly, scientists recognize that 90% of pathogens actually enter the body through the mucosa and secondly, we have evolved a mucosal defense system that can be used to defend against disease. There is now a better understanding of how to make that happen, along with generating the systemic system and blood titers that would be needed.
How are Mucosis’ vaccines going to be applied?
They can be applied through multiple routes including intranasal, orally or sublingual and there is even the possibility of vaccinating through the sexual organs, although that type of route obviously would not be the easiest route to use. Therefore, we are focusing on intranasal and oral routes at the moment and particularly intranasal because our focus is on respiratory tract pathogens. For those, we use drops or sprays to apply the vaccine.
Could you please outline Mucosis’ vaccine platform and how this is based on bacterium-like particles?
The platform is built around bacterium-like particles. These particles are made of a food-grade bacterium, which is the lactic acid bacterium used in cheese-making, for example. It's therefore a very safe bacterium.
Nevertheless, such bacteria are able to stimulate the immune system, so the bacterial particle is still able to trigger what is called the innate immune system. Triggering of the innate immune system is needed to set the adaptive immune system in motion and achieve long-lived responses.
Since this particle has common bacterial structures that are recognized by the innate immune system, it is able to stimulate it and direct the immune response towards the antigens, which are co-formulated with this particle. The antigens come from the pathogen, so this is a protein that we produce separately and then combine with the bacterium-like particle.
At what stage of development are Mucosis’ vaccines at?
We have one vaccine that has entered human trials for protection against influenza and we have another one for respiratory syncytial virus (RSV) that is just about to enter human trials.
The influenza vaccine we have used, which is an intranasal vaccine, gave us the data to demonstrate that the platform is safe and efficacious and does what we expected. As well as the systemic antibody response achieving protection against influenza, local antibodies in the nose can also contribute to protection.
To demonstrate in humans that these local antibodies do contribute to protection requires a lot more work and a lot more clinical trials. Therefore, we are now focusing on the RSV vaccine, for which no vaccine is yet available. The first clinical trial for that is planned for next year, in 2016.
How many other companies are developing needle-free vaccines?
There are only a few. There is a needle-free flu vaccine on the market in the form of an intranasal vaccine. There are also a couple of oral vaccines. All these vaccines are based on the pathogen itself, either an attenuated or dead form of it. Our vaccine, on the other hand, only contains one protein component of the pathogen, so it is much safer in that respect.
Our RSV vaccine differs from the ones other companies develop. I think we are one of the few that focus on an intranasal vaccine and I think this is very relevant, particularly for RSV.
New data has shown that there's a defect in the mucosal immune system in humans with RSV and our target is to fix that defect in the mucosal defense against RSV. That's not something that can be achieved using traditional injected vaccines.
I'm not saying that the traditional vaccines don’t offer any protection at all, but I think that an intranasal vaccine will have a higher efficacy. I think that's really pivotal in this RSV vaccine story.
What do you think the future holds for vaccines? Do you envisage a needle-free future for all vaccines?
I think in the future, we will begin tackling more difficult diseases. In many cases, although the progress we've made has been very good, it has been referred to as “capturing the low-hanging fruit.” I think we've got much more difficult diseases to pursue, such as RSV, and we will do that as an industry.
I also think we're going to improve on existing vaccines. For instance, when delivering the HPV vaccine to young girls, you actually need several doses for it to be effective and the compliance rate for that is very low. Here in the US, I believe the CDC said the compliance rate is somewhere around 30%, so these girls are not really protected, yet we're still paying for that first dose.
By giving them a mucosal vaccine, for instance, as a follow-up that they can deliver themselves a month later when they require the next dose, the compliance rate would go up. That's an example of one way to improve upon existing vaccines.
I think another way is to improve efficacy and if we find that mucosally-delivered vaccines for influenza or other infections improve the efficacy of those vaccines and ultimately save lives, then I think vaccines will change in that way.
Do I envision a needle-free future for all vaccines? No, I think that many of the vaccines that exist today will continue to do so, but I do believe for the same reasons I mentioned before, that others will move to needle-free, and in particular, mucosal delivery. For some particularly difficult diseases such as HIV, you may also see a combination of a needle-free and traditional vaccine.
What are Mucosis’ plans for the future?
We will focus on the RSV vaccine called SynGEM and develop that through human trials. Then, we'll look to partner that for commercialization. During that process, we'll continue to focus on introducing other new vaccines built on the platform that we've described.
We are a privately-held Dutch-based company and our investors are a combination of Dutch investors and one large Chinese manufacturer called BCHT. As would be expected in the biotech industry, we are in the process of continuing to raise funds as we make our way through our plan.
Where can readers find more information?
About Thomas Johnston and Dr. Kees Leenhouts
Mr. Thomas Johnston is Chief Executive Officer. Mr. Johnston joined Mucosis in May 2011 from Novavax where as Vice President of Strategy he developed and executed a regional partnership strategy with deals in India, Mexico, and South Korea.
Prior to Novavax, Mr. Johnston served as an executive-level strategic consultant in a number of industries including biotech, and held various senior-level positions with a number of world-class organizations such as Comcast, Microsoft, and Schlumberger.
Mr. Johnston holds an M.B.A. from The Wharton Business School and a Bachelor of Science degree in Computer Science from Arcadia University.
Dr. Kees Leenhouts is a co-founder and Chief Scientific Officer of Mucosis. Previously, Dr. Leenhouts was program manager at Biomade Technology Foundation, and responsible for intranasal vaccine technology development.
He spent two years as research fellow at the International Centre for Genetic Engineering and Biotechnology in Trieste, Italy. Dr. Leenhouts is inventor of the Mimopath® technology. He holds a Ph.D. in biology from the University of Groningen.