In Conversation with Barry Marshall: using pathogens to help humans

Nobel Laureate Barry Marshall discovered that peptic ulcers were caused by a bacteria called Helicobacter pylori. He is using the same bacteria to create probiotics and edible vaccines.

Marshall was in Indonesia on March 14 to 16. After giving a lecture at the Eijkman Institute for Molecular Biology in Jakarta, he spoke to Professor David Handojo Muljono, Eijkman’s deputy director for translational research who, like Marshall, is a clinician as well as a scientist.

David: Your discovery of H. pylori as the cause of gastric ulcer was a great contribution to the world. But it did not stop there: you have utilised a pathogen that “gives problems” to humans as a tool to help humans. How did the vaccine development begin?

Barry: The idea of delivering a vaccine with a bacterial vector [the use of bacteria as a vehicle for an element (gene or fragment of interest) of a microorganism by inserting it into the bacteria to induce immunity] has been around for 30 years. The beautiful thing about those vaccines is that you just take them in a drink and it gives you some protection by giving you a very mild infection and generating an antibody response.

But it may not be very effective the second time you have it because your body will quickly eradicate the vaccine strain.

When I looked at some of the data on the AIDS vaccination trials on HIV, it seemed to me the problem was that patients needed lots of boosters. If they have three of four or five or six boosters, maybe they would have enough immunity response to battle the HIV or to protect them from the HIV. But it’s not practical to give so many vaccinations.

At that point we were looking at Helicobacter and thought, well hang on a minute, Helicobacter infects you all your life and most people with Helicobacter don’t have the symptoms. In fact, at any point in time 80% of people feel fine.

We thought if you could put and find a harmless Helicobacter and clone in the HIV vaccine, or whatever vaccine you wanted really, you could give it to somebody and they would have a harmless Helicobacter infection and over many months the antigen will continue to be presented and it will be like having a booster every day.

It seemed a good idea to try. But we found some of our vaccine strains still were a little bit harmful. So we did not find a totally harmless Helicobacter.

However, I think the door is still open for us to use that strategy in specific diseases and specific antigens.

David: And other diseases such as hepatitis might be possible…

Barry: It’s still a unique idea with possibilities.

There is a good story related to this. When one of our patients developed an ulcer, it convinced us we needed to look at our data more carefully. We noticed in one of our experiments, looking at the immune system, we had a control group which had killed Helicobacter.

And we notice there’s an immune suppression in the killed Helicobacter almost as strong as immune suppression we sometimes see with live Helicobacter.

So, if Helicobacter activates T-regulatory cells and creates some immune suppression and switches the emphasis of the immune system in that way, well the killed Helicobacter seems to have an effect and would be 100% safe without the live [Helicobacter] problem.

So we switched over to that because there was a paper in New York which showed children with Helicobacter have reduced risk of any allergic disease.

And so, at least in mouse models, you can suppress the allergic response in mice with Helicobacter products. Live Helicobacter is the strongest but a little bit dangerous. But killed Helicobacter, we think, are 100% safe and still have a mild suppression to the immune response to allergens in the mouse models.

Now we’re creating a product that’s really an extracted product of H. pylori. We have to kill the H. pylori but the immune system still thinks it’s alive.

In Western countries, food allergies and different kinds of allergies are becoming more and more common in children. We think this kind of product in the first year of life, from six to 12 months for maybe three months' time, given as a food additive or something like an oral medication that children might take easily, might switch the immune system back to the more “stone age” natural one, instead of the child being exposed to all kinds of infections.

David: And what about the vaccine?

Barry: The vaccine, we still have it up our sleeve and it’s going to be useful in special severe cases in different diseases, because certainly the live Helicobacter will be the strongest. But the killed Helicobacter is 100% safe.

David: How has industry responded to these innovations?

Barry: At the moment, it’s going to stay in academic research. The problem with Helicobacter, you probably have one infection in your life and so that means if you have the vaccine, you only need it once.

For a pharmaceutical company a flu vaccine is good because you give it each year. But a vaccine that you only use once in your life that’s not the sort of drug that drug companies get very excited about.

But countries and the World Health Organisation might be interested in that kind of thing. [It’s] still a great research project in principle.

EDITOR’S NOTE: This interview has been edited and condensed.