If the cause is worthwhile, Professor Barry Marshall seems to enjoy upsetting the establishment. His 2005 Nobel Prize for Physiology or Medicine was awarded for his role in the discovery of Helicobacter pylori bacteria as the cause of stomach ulcers, research that upset the medical establishment for over a decade.
Three years after his Nobel award, Professor Marshall is continuing to challenge science’s dominant thinking, and instead of chasing a vaccine for Helicobacter infection, is using Helicobacter as a vehicle to prevent other infectious diseases.
His biotechnology company, Ondek, established during 2005, aims to develop new platform technology that will use the Helicobacter bacterium to deliver vaccines orally.
“The main issue with [vaccines based on] live bacteria or live vectors is safety,” says Professor Marshall.
“We already know that half the people in the world are infected with Helicobacter and also what happens when you have Helicobacter – usually nothing in the acute stage, or very little… Only many years later you might get an ulcer.
“The possibility then arises to use that usually harmless bacteria to deliver a vaccine.”
Because the natural environment of Helicobacter pylori bacteria is the stomach lining, vaccines using based on H. pylori as the delivery vehicle for the antigen offer several advantages. Firstly, they deliver vaccine antigens directly to the mucosal surface of the stomach, in close proximity to important tissues in the gastric tract, helpers in the body’s immune defence.
Secondly, they can be administered orally, avoiding the use of needles.
Thirdly, using H. pylori vaccines means immunisations against several diseases can be given in one easy dose.
Other bacterial vaccine vectors currently in use, a cholera vaccine based on a disabled cholera organism and a typhoid vaccine based on a disabled typhoid organism, are potentially more dangerous and difficult to use, notes Professor Marshall.
“With Helicobacter, if we want to make a typhoid vaccine, we would clone a typhoid antigen onto Helicobacter’s surface and [the vaccine] would protect you from typhoid. If you want a cholera vaccine, you’d put a cholera antigen on the surface and it would be a cholera vaccine.”
“Nobody else has a bacterium which can be used to deliver different vaccines,” he adds.
Testing of a multi-valent, oral vaccine for travellers, which combines immunisations against Hepatitis B, cholera and possibly Hepatitis A, is one of the first projects for Ondek. A flu vaccine is also a high priority for the Western Australian-based team. Their strategy is to put a DNA construct for flu antigen inside a Helicobacter bacterium, so it expresses the flu antigen on its surface.
Once this modified bacterium is administered orally to the patient, using a yogurt style drink or as a capsule, the modified Helicobacter will present the antigen to the immune system through the mucosal surface of the stomach. Ondek’s first commercial product will be seasonal-specific flu vaccines, which can be produced in large volumes within weeks and very inexpensively.
Ondek’s next target are immunotherapies based on this H. pylori delivery platform.
“Any autoimmune disease could lend itself to modification or amelioration by putting an appropriate antigen in the gut,” says Professor Marshall.
“In some respects, if you put a product in the gut and hammer it through the stomach wall, your immune system might approach it and say, ‘That looks like food, we’ll ignore it.’ You might be able to down-regulate the immune system to help rheumatoid arthritis, colitis, even allergies, asthma or atopic eczema.”
The idea for Ondek’s H. pylori platform technology came after Professor Marshall observed other scientists trying to create immunisations to prevent Helicobacter infection.
“For about 15 years, people were trying to build vaccines against Helicobacter and getting nowhere,” says the Professor.
The Ondek team realised that those experiments had generated a great deal of important information about the host-bacteria relationship in the process.
“No one really understands the human immune system, it’s a black box. However, Helicobacter DOES understand the immune system – it’s able to persist in your stomach lining all your life. [My approach] was, ‘Let’s learn from it and use it to our advantage’”.
“The idea of using H. pylori to deliver a vaccine started a brainstorming session until we had about 30 things we could do with this unique bacterial species. And whenever I explain the idea, other medical scientists come up with different applications we hadn’t thought of.
“We turned the Helicobacter vaccines project on its head with this new strategy.”
Ondek is currently raising 10 million AUD to begin clinical trials with their platform technology and will soon have a publication validating some of their recent work. Proof-of-principal and small clinical trials should be complete within two or three years, at which point Professor Marshall’s team hopes to attract a big commercial partner to fund the vaccine’s licensing and the larger regulatory studies. A final product would be between five and eight years away.
While Ondek’s success is personally satisfying for the entrepreneurial Nobel Laureate, it also features strategically in Professor Marshall’s vision for Australian science.
“My dream would be to have a substantial biotech in Australia as a result of the technology we’re researching now, something like CSL, ResMed or Cochlear,” he says.
In comments made to the Nobel Foundation during the week he and collaborator Dr Robin Warren were awarded their prize, Professor Marshall observed that there was a scarcity of commercially-owned biotechnology companies employing scientists in Australia.
“It just worries you that good scientists are coming out of universities … and other than teaching students, there aren’t any jobs for them. They’re going to all the corners of the earth. They have to follow the money …,” he said.
With the resources and good will won with the Nobel Prize, Ondek was Professor Marshall’s response to the problem facing Australia’s scientific workforce. His company became not just a vehicle for developing new technology, but a practical and long-term contribution to giving Australia’s scientists an opportunity to exercise their talents here, and a new attraction to the best of the world’s biotech experts.
“Ondek’s next step is to lay out the plan and continue to attract an excellent scientific team,” says the Professor.
“The Australian dollar is strong, salaries are good and conditions are very nice down here for scientists… Nowadays Australia is a great environment for a research career.”
Photo credit: Frances Andrijich
Related articles:
If the cause is worthwhile, Professor Barry Marshall seems to enjoy upsetting the establishment. His 2005 Nobel Prize for Physiology or Medicine was awarded for his role in the discovery of Helicobacter pylori bacteria as the cause of stomach ulcers, research that upset the medical establishment for over a decade.
Three years after his Nobel award, Professor Marshall is continuing to challenge science’s dominant thinking, and instead of chasing a vaccine for Helicobacter infection, is using Helicobacter as a vehicle to prevent other infectious diseases.
His biotechnology company, Ondek, established during 2005, aims to develop new platform technology that will use the Helicobacter bacterium to deliver vaccines orally.
“The main issue with [vaccines based on] live bacteria or live vectors is safety,” says Professor Marshall.
“We already know that half the people in the world are infected with Helicobacter and also what happens when you have Helicobacter – usually nothing in the acute stage, or very little… Only many years later you might get an ulcer.
“The possibility then arises to use that usually harmless bacteria to deliver a vaccine.”
Because the natural environment of Helicobacter pylori bacteria is the stomach lining, vaccines using based on H. pylori as the delivery vehicle for the antigen offer several advantages. Firstly, they deliver vaccine antigens directly to the mucosal surface of the stomach, in close proximity to important tissues in the gastric tract, helpers in the body’s immune defence.
Secondly, they can be administered orally, avoiding the use of needles.
Thirdly, using H. pylori vaccines means immunisations against several diseases can be given in one easy dose.
Other bacterial vaccine vectors currently in use, a cholera vaccine based on a disabled cholera organism and a typhoid vaccine based on a disabled typhoid organism, are potentially more dangerous and difficult to use, notes Professor Marshall.
“With Helicobacter, if we want to make a typhoid vaccine, we would clone a typhoid antigen onto Helicobacter’s surface and [the vaccine] would protect you from typhoid. If you want a cholera vaccine, you’d put a cholera antigen on the surface and it would be a cholera vaccine.”
“Nobody else has a bacterium which can be used to deliver different vaccines,” he adds.
Testing of a multi-valent, oral vaccine for travellers, which combines immunisations against Hepatitis B, cholera and possibly Hepatitis A, is one of the first projects for Ondek. A flu vaccine is also a high priority for the Western Australian-based team. Their strategy is to put a DNA construct for flu antigen inside a Helicobacter bacterium, so it expresses the flu antigen on its surface.
Once this modified bacterium is administered orally to the patient, using a yogurt style drink or as a capsule, the modified Helicobacter will present the antigen to the immune system through the mucosal surface of the stomach. Ondek’s first commercial product will be seasonal-specific flu vaccines, which can be produced in large volumes within weeks and very inexpensively.
Ondek’s next target are immunotherapies based on this H. pylori delivery platform.
“Any autoimmune disease could lend itself to modification or amelioration by putting an appropriate antigen in the gut,” says Professor Marshall.
“In some respects, if you put a product in the gut and hammer it through the stomach wall, your immune system might approach it and say, ‘That looks like food, we’ll ignore it.’ You might be able to down-regulate the immune system to help rheumatoid arthritis, colitis, even allergies, asthma or atopic eczema.”
The idea for Ondek’s H. pylori platform technology came after Professor Marshall observed other scientists trying to create immunisations to prevent Helicobacter infection.
“For about 15 years, people were trying to build vaccines against Helicobacter and getting nowhere,” says the Professor.
The Ondek team realised that those experiments had generated a great deal of important information about the host-bacteria relationship in the process.
“No one really understands the human immune system, it’s a black box. However, Helicobacter DOES understand the immune system – it’s able to persist in your stomach lining all your life. [My approach] was, ‘Let’s learn from it and use it to our advantage’”.
“The idea of using H. pylori to deliver a vaccine started a brainstorming session until we had about 30 things we could do with this unique bacterial species. And whenever I explain the idea, other medical scientists come up with different applications we hadn’t thought of.
“We turned the Helicobacter vaccines project on its head with this new strategy.”
Ondek is currently raising 10 million AUD to begin clinical trials with their platform technology and will soon have a publication validating some of their recent work. Proof-of-principal and small clinical trials should be complete within two or three years, at which point Professor Marshall’s team hopes to attract a big commercial partner to fund the vaccine’s licensing and the larger regulatory studies. A final product would be between five and eight years away.
While Ondek’s success is personally satisfying for the entrepreneurial Nobel Laureate, it also features strategically in Professor Marshall’s vision for Australian science.
“My dream would be to have a substantial biotech in Australia as a result of the technology we’re researching now, something like CSL, ResMed or Cochlear,” he says.
In comments made to the Nobel Foundation during the week he and collaborator Dr Robin Warren were awarded their prize, Professor Marshall observed that there was a scarcity of commercially-owned biotechnology companies employing scientists in Australia.
“It just worries you that good scientists are coming out of universities … and other than teaching students, there aren’t any jobs for them. They’re going to all the corners of the earth. They have to follow the money …,” he said.
With the resources and good will won with the Nobel Prize, Ondek was Professor Marshall’s response to the problem facing Australia’s scientific workforce. His company became not just a vehicle for developing new technology, but a practical and long-term contribution to giving Australia’s scientists an opportunity to exercise their talents here, and a new attraction to the best of the world’s biotech experts.
“Ondek’s next step is to lay out the plan and continue to attract an excellent scientific team,” says the Professor.
“The Australian dollar is strong, salaries are good and conditions are very nice down here for scientists… Nowadays Australia is a great environment for a research career.”
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