Research Profile - Planting vaccines: Making inexpensive virus-like particle vaccines in plants
A new vaccine against an infectious disease usually brings new hope. But the cost of producing and distributing the vaccine may put it beyond the reach of millions of people in the developing world.
That's why Dr. Brian Ward, a professor and associate director of the Research Institute at the McGill University Health Centre, is so excited about his work with a Medicago, a small Quebec biotechnology company. Together, they are developing cheaper, plant-based vaccines against influenza and several other respiratory viruses including respiratory syncytial virus (RSV).
At a Glance
Who: Dr. Brian Ward, Professor, McGill University; Associate Director, The Research Institute of the McGill University Health Centre, Montreal.
Issue: Vaccines to protect people against influenza or to immunize infants and children against common respiratory viruses, like RSV, could save millions of lives around the world every year. RSV kills 1-2 million children each year and early infection is implicated in the development of asthma.
Approach: In a close collaboration with Medicago Inc., a small biotechnology company in Quebec City, Ward and his team in Montreal are working to develop virus-like particle vaccines made in plants. These tiny ‘nanoparticles’ not only deliver the vaccines but also act as adjuvants (helpers that boost the immune system).
Impact: Using plants in the manufacture of these vaccines makes them faster and much cheaper to develop. These advantages may help to ensure greater accessibility to vaccines for those in the developing world who can’t afford the more expensive products, such as egg-based vaccines used to battle influenza.
RSV is the most common reason for hospitalization in the first year of life, and accounts for most of the 12,000 hospitalizations each year in Canadian children under two.1 Increasingly, RSV is also recognized as a serious threat to the elderly. The virus kills more than a million infants around the world every year, and has been implicated in the later development of asthma in people who are exposed at an early age.
In their hunt for new and cheaper vaccines to combat RSV and other serious viruses, Ward and Dr. Louis Vezina, a plant molecular biologist and co-founder of Medicago Inc., are using a close relative of the tobacco plant, called Nicotiana benthamiana, to produce a range of nanoparticle vaccines that 'look like' viruses but are not infectious. They infect the tobacco-like plant with bacteria carrying a small piece of viral genetic information. The plant then produces viral proteins that assemble on the surface of the plant's cells in tiny, fuzzy little balls that are about 100-150 nanometres in diameter - about the size of a virus, too small to be viewed with the naked eye.
The 'fuzzy' surface of these particles consists of viral proteins that stimulate the immune system to make antibodies. The researchers then harvest the virus-like particles (VLP) and use them directly as a vaccine. Although these particles aren't infectious, when injected into animal models or humans, they trigger an immune response that can protect against infection.
Ward and Vezina's first plant-produced virus-like particle vaccine against the potentially dangerous H5N1 bird influenza has just been tested in humans at the McGill University Health Centre's Vaccine Evaluation Centre. The volunteers in the study tolerated the vaccine well, and it produced excellent antibody responses, says Ward.
If on-going clinical trials verify the promise of these plant-made virus-like particles, these novel vaccines will not only be faster to produce than the current generation of vaccines, they will cost much less to manufacture - making them more accessible to the developing world.
"The current lag time to get a vaccine that we use routinely in Canada into the developing world is 15-18 years," says Ward. "These vaccines made in plants could, in theory at least, reduce the cost of making these vaccines by an order of magnitude which is huge."
Influenza vaccines, for example, are not routinely offered in any developing country. "I'm hugely enthusiastic about this project," adds Ward.
Several candidate influenza vaccines that Ward and Vezina have tested in animals not only protected them against the virus they were targeting, but also against related viruses, he says. Ward believes this kind of vaccine could also work against other viruses such as rabies, yellow fever and dengue fever.
In the case of an influenza pandemic, such as the recent outbreak of swine-based H1N1, these plant-made VLP vaccines would also have the advantage of speed. The traditional way of making influenza vaccines requires the pandemic virus to be adapted for growth in eggs, a process that can take months. By contrast, a candidate plant-based virus-like particle vaccine could theoretically be produced within two to three weeks, says Ward.
Although egg-based vaccines for the H1N1 pandemic were developed and distributed in 2009-10, it took months to generate the first doses and the pace of production was too slow to satisfy the world's needs. Had the pandemic strain been more deadly, each month of production time would have been measured in lives lost.
Ward hopes that this promising technology will not only ensure better preparation for the next pandemic, it may also permit the development of new vaccines for RSV and other viruses, and ensure they will be affordable and accessible for all.
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