While extraordinary, the timely arrival of a COVID-19 vaccine developed by the German company BioNTech in partnership with U.S.-based Pfizer Inc. after its speedy path through clinical trials and regulatory approval is no fluke. The fact that a handful of other vaccines are well along the same path – and close behind in the case of the vaccine made by Moderna Inc. – shows the power of an entire industry focusing on one overriding problem.
“This whole thing has been remarkable,” said Mark Lievonen, a former president of Sanofi Pasteur Ltd. and co-chair of Canada’s vaccine task force, which advised the federal government on which vaccines to buy last summer. As recently as one month ago, Mr. Lievonen was prepared to say that the first Canadians could be vaccinated next year “before the snow melts.”
Even that seemed optimistic in early November. The timeline to develop a vaccine and get it to market varies greatly, but it can average 10 to 15 years, according to Scott Halperin, director of the Canadian Centre for Vaccinology in Halifax. Yet the Pfizer-BioNTech vaccine has arrived in about one-twentieth that amount of time, with the first inoculations expected within days.
How can this have been achieved without sacrificing safety? The answer comes not from skipping steps but from a massive optimization effort in which many of the stages that typically happen in sequence are conducted in parallel.
It also helps that the front-runners had a huge head start with technologies that were already in development for other applications. Even the RNA vaccines made by Pfizer-BioNTech and Moderna, which represent a new type of vaccine strategy, are the product of many years of research.
“A lot of the basic science and the understanding of how these vaccines work was done before COVID-19,” Dr. Halperin said.
BioNTech’s story is a case in point. The idea of injecting people with a copy of an RNA sequence from a virus to generate an immune response to that virus is an elegant solution and one that has been around for more than two decades, said the company’s founder and chief executive officer, Ugur Sahin. The challenge he and his wife undertook was figuring out how to get the fragile strands of RNA into cells reliably where they could be taken up to make viral proteins that in turn would trigger the body’s immune response. Many innovations were needed, rather than one key breakthrough, including a lipid coating developed by a Canadian company, Acuitas Therapeutics, that forms a protective envelope around the RNA when it enters a cell.
Their goal was developing vaccines to prompt the body to attack cancer cells. And because each patient’s cancer is genetically unique, the process had to be good at handling something different each time and taking it to a working vaccine in about four weeks.
“This is on-demand manufacturing,” Dr. Sahin said. “We get the tumour sample of the patient, we extract the genetic information and then prepare the vaccine in the shortest possible time.”
When a new type of coronavirus showed up earlier this year, Dr. Sahin said he knew that his team could be as fast as anyone in the world, perhaps even the fastest, at coming up with a vaccine.
What he and other vaccine makers needed was a target to aim at – something that Chinese researchers provided when they sequenced the genetic code of the coronavirus and made it available worldwide on Jan. 11 of this year, about one month after the outbreak began.
Prior experience with the original SARS coronavirus in 2003 meant that scientists could guess that they would have promising results with a vaccine based on the coronavirus spike proteins – the knobby protrusions that cover each virus particle and are the first thing the human immune system detects when an infection is under way.
While their approaches are diverse, all of the vaccines that Canada has arranged to purchase over the coming year are ultimately based on exposing the immune system to the coronavirus spike protein or some portion of it. Within a matter of weeks, those who were already set up to develop vaccines, including in Canada, were testing their top candidates in lab animals.
By April, the World Health Organization had published the criteria that the COVID-19 vaccines would need to meet to be deemed worth distributing, including an efficacy of at least 50 per cent. That gave vaccine makers and regulators a bar to measure against.
Karen Mossman, a biochemist at McMaster University in Hamilton who specializes in viruses, said many of those candidates were helped during early-stage clinical trials by factors that are often in short supply when vaccines are being developed, including funding and industry partners with manufacturing capability.
“It’s not just how quickly can you make something, but how quickly can you get the resources?” she said. “This was a case of all hands on deck.”
As early clinical trials wrapped up for Pfizer-BioNTech and other front-runners last summer, governments stepped up with their orders. For the companies, this removed the risk of scaling up production even before large-scale clinical trials were finished.
This last step – unfortunately – was helped along by the pandemic itself, which began surging in many countries just as large-scale Phase 3 clinical trials were getting under way there.
Testing a vaccine requires the presence of disease to test against. Each trial has to meet milestones based on how many of the tens of thousands of people in the trial ended up getting COVID-19. Once the milestone is hit, researchers check to see how many of those individuals received the vaccine versus how many were given a placebo.
During Moderna’s trial those milestones were reached about four weeks ahead of projections, simply because infection rates have climbed so steeply in the United States. Dr. Sahin said it was a similar story with his vaccine. He originally hoped to have clinical trial data in hand by the end of December, but instead it came two weeks ago, setting the stage for regulators at Health Canada to complete their review.
Manish Sadarangani, director of the vaccine evaluation centre at the BC Children’s Hospital, said the speed at which all the steps were completed can be compared to making a Hollywood blockbuster. While it may normally take years to acquire rights, raise money and assemble a director, cast and crew for a project, the actual filming and editing can be done in a few months.
“And if you had every studio in Hollywood just focusing on making one movie, then stuff can happen pretty quickly,” he said.
The Globe and Mail, December 9, 2020