Now is the time to build domestic vaccine capacity: drug developers

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When the United States Department of Agriculture posted hundreds of genetic sequences from the expanding H5N1 avian flu outbreak in April, Michael Warobey, a Canadian evolutionary biologist based at the University of Arizona, pulled an all-nighter.

He was on holiday with his family at the time, and the intrusion of work was not popular. But Warobey, who heads the university’s department of ecology and evolutionary biology, knew it was crucial to better understand the evolving avian influenza outbreak in U.S. dairy cattle as quickly as possible. He was among those scientists racing to interpret the genetic material.

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What they learned was worrisome. It became clear that the cows — more than 65 dairy herds in the U.S. have now been infected, along with three farm workers — were not sick as a result of isolated infections, but rather were part of a single outbreak of the highly pathogenic avian influenza H5N1. It had been spreading through cattle in the U.S. for much longer than originally thought. Maybe as far back as November, Warobey says.

“This is months and months of this virus getting better at infecting mammalian cells. It is months and months of exposure of humans to millions of dairy cattle that exist across the country,” he says.

Those months of spreading under the radar — and potentially changing to become more easily spread to humans — brought the world closer to the possibility of an avian influenza pandemic.

“Damn it, we are not getting better at these things. In many ways, we are getting worse. We have lost how many months preparing for the possibility that we will need vaccines,” Warobey says.

The Canadian evolutionary biologist has become a key voice sounding the alarm about the need for governments to move more quickly and to invest more in research, surveillance and production in order to prevent or at least get ahead of a possible avian influenza pandemic. He and other researchers, he says, are “swimming upstream” to piece together funding for research and not enough proactive action is being taken.

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“Our whole system is reactive rather than proactive and, if there is any problem in the world you need a proactive approach for, it is preventing pandemics,” he says.

“We need to assume this is going to start spreading in humans and building up stockpiles of vaccines that can be deployed.”

He says billions of dollars should be invested in pandemic prevention and preparation. The British Columbia native says more needs to be done in Canada, as well as the U.S., to understand the ongoing situation, to prevent the spread of avian influenza and to prepare for a possible pandemic.

His concerns are amplified by some Canadian drug developers and vaccine biomanufacturers who say there is an urgent need for Canada to invest more broadly in research and to build domestic vaccine manufacturing capacity as the risk of an avian flu pandemic grows.

They include John Fulton, a Niagara-based drug developer and pharmaceutical industry consultant who is working on multiple projects, including plans to develop an avian flu vaccine.

Fulton, who worked with a Canadian company to produce generic influenza antivirals during an earlier bird flu virus, says he “hasn’t had a good night’s sleep” since evidence began to mount about the pandemic potential from ongoing outbreaks of avian flu.

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He says the federal government has been slow to act, despite having plenty of warning about the potential risks of H5N1. That includes a study done in the National Microbiological Labs showing a strain of avian influenza taken from a hawk spread easily among mammals (ferrets) in a lab setting. The research, released in preprint last year, set off alarms that H5N1 might be able to spread among humans as well.

The group also includes vaccine manufacturer Donald Gerson and his son Jonas, founders of the Montreal biotechnology company PnuVax, which failed to get federal government support to produce COVID-19 vaccines for Canada. Gerson previously produced 350 million doses of smallpox vaccine for the U.S. national stockpile after 9/11.

Fulton says there are three Canadian vaccine manufacturing facilities available to the group that could produce avian influenza vaccines for humans or animals with government support.

Since those H5N1 genetic fragments were released, the avian flu outbreak has evolved rapidly, with growing numbers of cattle herds infected and, to date, two dairy workers. Among worrisome findings was a notable mutation in the virus found in the second infected dairy worker. Recently, an Iowa egg farm infected with avian influenza was forced to kill four million chickens.

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In the U.S., inactive avian flu virus has been found in a significant proportion of retail milk samples, indicating the spread of the virus in cows might be broader than reported. No fragments of the virus have been found in milk tested in Canada. Wastewater researchers in the U.S. are also beginning to monitor for signs of H5N1 in sewage. Canadian wastewater researchers say they are also prepared to begin monitoring for H5N1, if needed.

The risk to human health is still considered low by health officials. But there are growing fears that the spread of H5N1 among domestic animals in close proximity to people could result in genetic changes, allowing it to more easily infect and even to spread in humans, particularly by becoming better at infecting cells in the upper respiratory tracts of humans, which is how viruses frequently spread.

The implications of that, for both human and animal health in Canada, would be huge, Fulton says. Not only does Canada have a massive dairy and cattle industry that could be affected, but flu vaccines — including pandemic flu vaccines — are largely made using eggs in Canada.

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Fulton and Gerson want to produce cell-based vaccines, which use animal cells to grow flu viruses rather than hens’ eggs. Influenza vaccines have long been made using hens’ eggs kept in sterile and secure locations. Fulton and others say Canada’s sole reliance on egg-based flu vaccines for most of its supply could be risky during an avian flu pandemic.

Like many countries, Canada has pandemic influenza plans in place and plans for the manufacture of enough vaccines for the Canadian population. Public Health Agency of Canada (PHAC) spokesman Nicholas Janveau says that will prevent against the risk of vaccine embargoes, border closures and transportation and shipment delays.  PHAC also says it is working proactively on “preparedness and potential response to human cases of avian influenza”.

But Fulton and Gerson say engaging domestic businesses like theirs should also be part of the preparation for a pandemic that has the potential to make humans sick and place parts of the agricultural industry at risk.

Fulton is seeking $40 million through the federal government’s strategic innovations fund for a $50-million pandemic vaccine project. He is testing a vaccine platform with the potential for both human and animal H5N1 vaccines. He has already applied once for the funding, but was denied. He now has $10 million in financial backing and is working with developers of a cell-based vaccine platform that could be used to make pandemic avian influenza vaccines if needed.

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“We need to be looking under every rock to get ahead of this pathogen,” he says.

Gerson says his plant could be ready to produce H5N1 vaccines quickly if it received funding. The PnuVax plant in Montreal sits next to the Biologics Manufacturing Centre, which was built on National Research Council of Canada land early in the COVID-19 pandemic. Amid discussions about lessening Canada’s dependence on foreign sources, it was built with a $130-million injection of public funding to produce COVID-19 vaccines — something it has yet to do.

Gerson, his son Jonas and Fulton say a domestic vaccine industry would protect Canadians during a potential avian flu pandemic and offer an alternative to egg-based vaccines.

Fulton says small- and medium-sized businesses should be key to building up Canada’s domestic industry.

“The real question is does Canada want to have domestic vaccine production facilities or does it want to continue to sponsor large multinational companies?” Jonas Gerson asked.

“Let us compete … so that we have multiple (vaccine) options. We could be part of the solution and be a net exporter (of vaccines).”

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The Public Health Agency of Canada says it is “continuing to assess” whether it will obtain pre-pandemic vaccines from GSK, the multinational pharmaceutical company that is contracted to produce seasonal and pandemic flu vaccines in Canada.

The U.S. and some European countries, meanwhile, are beginning to stockpile pre-pandemic vaccines and are looking at vaccinating agriculture workers and others at high risk.

Since COVID, the Canadian and provincial governments have invested in pandemic preparedness, including hundreds of millions of dollars for academic-based pandemic preparedness hubs, part of what the government says is a multi-billion investment in biomanufacturing, vaccines and therapeutics.

On Thursday, Prime Minister Justin Trudeau was among officials marking the opening of a vaccine production plant in Toronto which is expected to increase Canada’s domestic production of pediatric and adult vaccines for whopping cough, diphtheria and tetanus. The Sanofi facility is part of the country’s effort to build up the biomanufacturing sector in the aftermath of the COVID-19 pandemic.

The company received $415 million from Canada and $55 million from the Ontario government to build what will be the largest vaccine production plant in Canada. It is expected to be producing vaccines by 2027. A spokesperson says the company had the agility to “respond appropriately to a pandemic.”

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