Norovirus could soon be treated with a one pill vaccine

A new oral vaccine for norovirus has performed remarkably well in clinical trials. The pill - which has been developed by the pharmaceutical company Vaxart - is attempting to address the lack of safe and reliable vaccines for norovirus, which is a leading cause of gastrointestinal infections worldwide. In the UK it routinely costs the NHS close to £100 million per year, in cancelled operations, closed wards, staff sickness and by prolonging hospital stays for patients. It works by using a disabled “cold” virus to smuggle into the gut the genetic message for a part of the norovirus outer coat, fooling the body into thinking the infection is there for real and provoking an immune response. I’ve been speaking with Vaxart's Director of Immunology, Becca Flitter…

Becca - Our vaccine is an oral vaccine and it's a pill. It goes into the intestine and it stimulates your immune system in the gut to make protective responses, antibodies that attach to the virus, letting your immune system know like, hey, it's time to get this out of there.

Chris - What is actually in the pill that does that?

Becca - Our vaccine is based on an adenoviral vector, a non-replicating virus, and what it does is it holds the DNA of a norovirus protein that tells the cells in the gut to make the norovirus protein so that the immune system learns how to detect the protein code of the virus and make a response to it. It's very safe. We've done multiple human trials, and because it's a room temperature pill, it can easily be distributed. It can literally come to you in the mail or be distributed in the military quickly, and they're a great alternative to a needle-based injection that only provides immunity in the bloodstream, whereas our tablet, because it's released in the gut, is training your body to learn how to make a good immune response in the gut where the norovirus infects.

Chris - And how quickly does a person build a response once they've actually been exposed to the pill? And is it just a one hit? You take one pill, and that's enough to drive the immune response?

Becca - We've seen immune responses start by day eight, and then it peaks right around one month after vaccination. And those responses stay pretty high out for like three or four months, and then they start to decline, but they stay out until at least a year. Right now, we're working towards having one pill per year. Unfortunately, for norovirus, it's a very diverse sets of viruses, and so it's constantly evolving. So it'd kind of be like the flu shot or the flu vaccine where you go in once a year, but instead of getting a shot, you can just take a pill.

Chris - And does it actually work to protect people? As in, if you take this pill and then you are actually challenged with norovirus for real, do you not catch it, which has to be your goal here?

Becca - Phenomenal question. So in a recent paper that we just published, individuals in the placebo group who got a sugar pill had about 82% infection rate compared to the individuals who got vaccinated, that was a 57% infection rate. And I just want to caveat this with the fact that we challenged them with a really high amount of norovirus. It takes 10 particles to really make someone sick. In this particular study, we challenged them with over a million particles. So we were really aiming to make people infected.

And the reason we did that was to make sure that we could measure the immune responses very accurately and model them to know which ones were important for resisting infection.

Chris - One of the really big problems with norovirus is that it is the king of the shapeshifters, and it mutates so fast that it's impossible almost for our own immune systems to keep up, isn't it? So what's the evidence that if this were the real world and a group of people had your vaccine, but then were exposed to real norovirus evolution, not something you're infecting them with in the lab, that they would be protected for a reasonable period of time?

Becca - That's a fantastic question. So one of the things that our vaccine actually is really good at is something called cross-reactive immune responses. And we think this happens because our vaccine is targeting the gut, where it's likely most individuals have already encountered a norovirus infection. And not only does our vaccine stimulate new immune responses to the target protein that we're trying to produce antibodies against, but it also stimulates memory responses in individuals who've already seen norovirus. And we see an increase in the amount of immunity to multiple different types of norovirus. This gives us a lot of hope that our vaccine can actually be used for protection against multiple different norovirus circulating strains. So we're hoping to get broad cross-reactive protective responses using this vaccine technology.

Chris - Is the performance that you're getting going to be good enough to satisfy regulators and going to be economically viable?

Becca - We are in conversations with the FDA here in the United States and they're encouraging. And in terms of cost, we've made some significant strides in really making sure this vaccine does not cost a lot of money. And we want to make sure that this vaccine can be available all over the world, especially in areas where cold chain can be an issue. And so we really hope that some of this new data coming out, as well as the published results that we have put out this year for this norovirus vaccine, will really help convince the regulators in many different countries that this is a great solution to reducing the norovirus disease burden.