Using plants to develop dengue vaccines
Dengue fever, a disease that infects almost 400 million people worldwide every year, is Malaysia’s most prevalent infectious disease.
Carried by Aedes mosquitoes, the dengue virus causes severe headaches, muscle and joint pains, swollen lymph nodes, vomiting, fever and rash. In some cases, it can be life threatening.
With no promising treatment so far, a team of scientists from the University of Nottingham Malaysia has started working on a project to create a plant-based vaccine, which, if successful, would provide a safe and cost effective way to prevent this disease.
Research team leader Professor Sandy Loh said the project had produced a vaccine antigen (protein) within a plant that neutralised dengue virus.
She added that vaccines were created from proteins that could be produced in different systems, and research focused on mammalian cell, bacterial cell or fungus.
“Using plants for this process is a new emerging platform that has the potential to provide a vaccine that can be taken orally.
“Other than tobacco plants, we are also working on edible plant species, such as lettuce, which we hope will eventually lead to an oral vaccine in the future.
“This method of using plants to develop vaccines has many advantages, such as higher expression, lower production cost and easier distribution, as there is no need for trained nurses to provide injections. It is also safer as there are no animal or human pathogens which increases the biosafety aspect,” she added.
Loh, a virologist and molecular biologist from the university’s Faculty of Science, works with plant-based pharmaceuticals focusing on innovative treatments for dengue and avian influenza H5N1, which are diseases that are on the rise in tropical countries, such as Malaysia.
“My current project is to develop an ‘edible’ plant vaccine, which can be consumed orally by the patient. This is less invasive than using hypodermic needles, and you don’t need trained medical staff to administer it.
“The uniqueness of the project is the use of a transient expression process called agroinfiltration. During this process, a defective plant virus is combined with Agrobacterium in making an expression vector that delivers the dengue vaccine antigen into the leaf of a tobacco plant.
“It is then incubated and harvested. After a few days, the vaccine antigen can be extracted and purified for use as a vaccine,” she said.
Loh said the findings of the project had verified that an immune response was created using the plant-based vaccine in an animal model and the antibodies produced could neutralise the dengue virus.
The next stage of the research, she said, would involve virus challenge studies to determine the protection efficacy of the plant-based vaccine.
This technique has also been used to investigate plant based vaccine for avian influenza, and has had similar success.
“For developing countries, the development of a cost effective vaccine from plants would have a big impact as it would mean they can develop their own local vaccines to combat endemic diseases.
“Providing vaccines in this way would save many lives. Normally, we freeze-dry the protein, grind it into a fine powder then transfer it into a capsule so it can be taken as a pill, orally.
“The good thing about freeze-drying is you can store the vaccine at room temperature and it maintains its protective efficacy. There is no need for refrigerated storage or cold chain transportation, which is crucial in countries where electricity is scarce or unreliable.
“It has the potential to save many lives. For diseases like flu, which can mutate quickly, the speed at which we could potentially develop a vaccine is as rapid as one month. This means specific vaccines can be produced and be ready for any potential pandemic outbreaks,” Loh said.
Inspired by Professor Charles Arntzen of Arizona State University, who coined the term edible vaccine, she said Arntzen was the pioneer for people working in this field and he had sparked her interest in it many years ago.
“I started my research career by developing a vaccine against poultry viral disease. When I joined University of Nottingham Malaysia, I taught a plant biotechnology course. It changed the course of my research career, encouraging me to investigate plants and their potential as the next-generation vaccine platform,” she said.
Loh was the first female academic to be promoted to professor in the university’s Faculty of Science in 2015. She obtained a senior fellowship of the Higher Education Academy United Kingdom last year.
“There is still a long way to go. Upscaling will be the next step in our project, along with testing whether the antibodies in the vaccines are protective or not against the intended viruses.
“We need to crack these problems before we can proceed to clinical trial,” she said.
She said the project was interdisciplinary in nature.
“In addition, the plant biology methods we are using are well-established in the West, but are just emerging in Asia. We are working with colleagues from Nottingham, together with immunologists, virologists and biotechnologists from the John Innes Centre, UK, and the Fraunhofer, the United States Center for Molecular Biotechnology.
“Locally, I have collaborations with Universiti Putra Malaysia and Monash University Malaysia.”
