A research group in Maynooth College is working on new vaccines that can be eaten rather than injected with a needle, writes Claire O'Connell
Plants could be a future one-stop shop for making and delivering easy-to-swallow edible vaccines. Researchers in Maynooth are working towards generating lettuce plants that make a vaccine against a common bacterium which causes stomach ulcers.
"Edible vaccines may or may not be a reality, they may or may not work," says Dr Jacqueline Nugent, lecturer at NUI Maynooth's biology department. But using plant cells to make and deliver vaccines could turn out to be a valuable approach in protecting us against disease, and her team is currently recruiting tobacco and lettuce plants to make specific proteins that can stimulate the immune system in humans.
However one challenge with edible or orally delivered vaccines is how to overcome the harsh gut environment, which could destroy vaccines before they get to work in the body. So Nugent chose a vaccine that would act at one of the first hurdles, the lining of the stomach. She is working with NAP, a protein that can stimulate the immune system to protect itself against the bacterium Helicobacter pylori, which is a major cause of stomach ulcers worldwide.
It's a good system to test edible vaccines, Nugent believes. "If it's not going to work there it's not going to work anywhere," she says. "Around a plant cell you have a cell wall and it might protect your vaccine as it passes through the digestive system. It may potentially allow it to stay there long enough to be effective. These are the things we are interested in looking at."
One promising approach to create an edible vaccine is to turn the plant itself into a vaccine "factory" by inserting a specially constructed genetic blueprint for a therapeutic protein into tiny compartments called plastids, which occur plentifully in leaf cells. By slotting a specially constructed DNA code for the new protein into the existing DNA within the plastids, you could potentially end up with hundreds to thousands of copies of the new gene per cell, says Nugent.
The goal is to take a plant that can be eaten raw and engineer it to make therapeutic proteins. To test their methods, Dr Nugent's team has been using the rather unpalatable tobacco plant, a commonly-used workhorse for inserting genes into plastids.
Nugent and post-doc Dr Kim-Hong Nguyen inserted the genetic code for NAP into plastids in tobacco leaves, which went on to make the NAP protein. And they are starting trials of the NAP-making tobacco leaves to see whether they can indeed invoke an immune response in the gut.
In parallel experiments, Nugent's team were part of a project to insert new genes into plastids of the more challenging lettuce plant, which is a tastier possibility for delivering edible vaccines. PhD student Orlaith McGrath will now put the NAP gene into lettuce and see whether fresh or freeze-dried leaves from the modified plants can still stimulate the immune system through the gut. But we won't be chowing down on vaccines in our salad sandwiches - ultimately the minimally processed leaves would be delivered in controlled capsule form that could be especially useful in the developing world, explains Nugent.
She stresses the need to ensure these modified plants have a benign impact on the environment. Making use of the abundant plastids means each leaf can potentially produce large amounts of therapeutic proteins, so individual plants are used efficiently, she explains. "We are not envisioning fields of these plants. Most lettuce is grown under glass in contained conditions. You can get large amounts of biomass in a relatively small area."
The plastid approach also helps avoid the new genes accidentally entering other crops, because most plant species do not carry plastids in their pollen. "You don't have to worry about pollen escape because it's not going to carry the (new) gene, so that's another level of protection," she says.
The work is funded by the Health Research Board, IRCSET and the EU.