Canadian scientists are deliberately injecting influenza virus into the noses of human volunteers, joining other countries in studies of controlled infections in humans that, while accelerating vaccine development in preparation for future pandemics, are also raising ethical concerns.
The experiment, one of the first of its kind in Canada, involves exposing consenting adults to a dose of the seasonal flu virus, monitoring their symptoms and immune responses, prescribing antiviral drugs if necessary, and keeping volunteers in special isolation “pods” for at least a week until they test negative.
The tests are designed to give researchers a better understanding of how the pathogen behaves inside the human body to help improve existing drugs or vaccines or develop new ones.
The experiments have a long history in other parts of the world, having been used for decades to test potential treatments or vaccines for diseases such as infection and malaria.
In 2020, as COVID was spreading rapidly, British scientists conducted trials on people with COVID-19 by injecting young, healthy adults with vaccine candidates and then challenging them with SARS-CoV-2 when there were no proven treatments against COVID, raising ethical concerns about the “dual risks of exploitation and coercion.” Volunteers were paid the equivalent of $6,500 Canadian dollars to agree to be infected with COVID and then quarantined.
In Canada, Liberal MP Markus Powlowski, a former emergency room doctor, introduced a petition to Parliament signed by several Canadian infectious disease experts calling on the government to announce a plan for similar trials using the COVID-19 virus. The government responded that this would be particularly risky given the limited treatment options and the unknown long-term effects of the potentially “severe and deadly” virus.
“Because SARS-CoV-2 was really new—we were discovering its biology and its side effects in real time—I think there was a very reasonable hesitancy among many virologists, myself included, about the idea that we should start using it as a challenge strain,” said Dr. Brian Ward, co-principal investigator of the influenza challenge study.
In conventional vaccine studies, volunteers are vaccinated or given a placebo and then sent back into the real world to see how many of them are naturally exposed to the circulating virus. This approach is time-consuming and expensive, says Ward, director of the MUHC Vaccine Research Center (McGill University Health Centre).
In contrast, controlled studies of infections in humans require fewer volunteers and much less time because they do not rely on naturally occurring infections.
But Canada doesn’t usually run them. Ward and his co-author, Scott Halperin of Dalhousie University, spent two decades doing the groundwork to get them off the ground. Halperin recently conducted a controlled infection study in humans using Bordetella pertussis, the bacterium that causes whooping cough.
Canada first needed special isolation facilities, viruses and experience. “And then you have to convince everyone around you that it’s okay,” Ward said. “Each of these steps took a long time.”
The new project, in collaboration with the Canadian Center for Vaccinology at Dalhousie, began in June with the first eight volunteers in Halifax; two more participants have already started the study in Montreal. The study will ultimately enroll 32 people, 16 at each site, all healthy adults aged 18 to 45 who have no known risk factors for severe influenza, a disease estimated to cause 3,500 deaths annually in Canada.
The researchers use a weakened H3N2 virus that is diluted in glucose and saline and sprayed into the nose as an aerosol. Volunteers are studied intensively “from the moment we infect them,” Ward said. H3N2 is a subtype of influenza A. Influenza A viruses are on a short list of viruses that can cause global pandemics, Ward said.
Half of the volunteers receive a low dose; the other half, higher. One from each group of four people receives a saline placebo solution. At the higher dose, 60 to 70 percent of patients are expected to experience mild to moderate symptoms.
They all remain isolated for a minimum of seven days in specially designed negative pressure rooms that prevent potentially contaminated air or other indoor particles from circulating outside the room.
People are monitored 24 hours a day by one or two nurses and undergo regular blood tests and nasal swabs. The department is in touch 24 hours a day. “If these people show any signs of problems, we will immediately take action and start antiviral drugs,” he said.
The experiments will help better understand how the human body responds even within the first few hours to influenza, a “slippery family of viruses” that, unlike measles, “mutates like crazy,” Ward said.
“One of the big problems with understanding how our human body responds to any pathogen is that it is very difficult to know when someone has become infected,” Ward said.
Some volunteers who contract the flu show no symptoms at all. “That their bodies did the right thing to stop a possible infection before it started,” Ward said. “We can find early biomarkers of successful response.”
The team is not testing the vaccine in this round, but hopes to create a model for future vaccine trials, Ward said. “How do you recruit people to do this kind of research? How do you convince your research ethics board that it’s okay to do this?”
For example, in the event of a deadly influenza pandemic, “two, three, 10, 20 different vaccines” could be tested in a challenge trial to determine which provides the most individual protection and reduced community transmission, Ward said.
In a flu infection study, “you have to have a very frank conversation with the volunteers,” Ward said. “Because every now and then—extremely rare, but every now and then—a healthy person gets the flu and ends up in the intensive care unit because their body overreacts to that particular viral challenge.”
Ten percent of the world’s adults become infected with influenza each year. “That doesn’t mean we’re doing something that is unlikely to ever happen to you otherwise,” Ward said, but added that “we’re doing everything we can to mitigate” the risks.
While Ward said he was excited about the challenge ahead, “I wouldn’t be honest if I didn’t say I was pretty nervous too.
“Working with these volunteers, trying to do good science and making sure we don’t cause any harm is a little on the edge.”
Volunteers receive compensation commensurate with the seven to 10 days they give of their lives, Ward said, although he declined to give exact amounts.
The work is funded by a Canadian Institutes of Health Research Pandemic Preparedness grant.
National Post
Our site is the place for breaking news, exclusive news, long reads and provocative commentary. Bookmark nationalpost.com and subscribe to our newsletter here.