In April 2009, a new type of influenza began spreading through the American West: H1N1, or swine flu. Vaccine developers had been preparing for a moment like this after several deadly flu pandemics in the twentieth century. They began cultivating the virus for a new flu vaccine, and the vaccine was ready just a few months later in October. It still wasn’t fast enough to prevent a pandemic. Kids, who are among the most vulnerable to the flu, went back to school in September, and the swine flu spread around the world.
But what if vaccine developers didn’t have to wait months to cultivate a virus in eggs and then inactivate it for a vaccine as they did with swine flu? What if they already had an all-purpose base for a vaccine built and then they simply tweaked it whenever they learn about a new virus?
Almost half of the 193 vaccines in development for SARS-CoV-2, the coronavirus that causes Covid-19, follow this second model and are known as “platform vaccines.” Platform vaccines are like business suits that only need a little tailoring to fit perfectly; much of the work is done ahead of time, and all you need is for the wearer to tell you their measurements. In this case, those details are provided by genetically sequencing a virus—in a matter of days—and then customizing the platform within weeks.
Some governments and nonprofits have taken notice of platforms’ potential and committed vast sums to their development and manufacturing. The United States government has committed a total of $2.4 billion to Novavax and promised $1.2 billion to AstraZeneca to develop and potentially manufacture their platform vaccine candidates for SARS-CoV-2. The Coalition for Epidemic Preparedness Innovations, or CEPI, has also given $388 million to Novavax for research and development. The British government has committed more than $100 million so far to the University of Oxford’s SARS-CoV-2 platform vaccine candidate. All this despite the fact that the vast majority of potential vaccines—of any variety—never make it to the public. Typically, only 6 percent of new vaccines in development are successful.
Are we pinning all our hopes on an untested technology? Or does this represent a new era of faster vaccines? The experts I’ve talked to think it might be a bit of both. Platform vaccines have advantages in situations much like the one we’re in now. But the emerging technology could also be politicized and rushed to market too soon, leading to a backlash and erosion of public trust at a precarious moment.
“I think that platform technologies are the way to go,” Dr. Angela Rasmussen, a virologist at Columbia University, told me. The reason why vaccines from Moderna, Oxford, Johnson & Johnson, Pfizer and others “are all sort of winning the race is because they were able to start designing these vaccines, because they had these platforms ready to go as soon as they got the sequence on January 10,” she said. “They didn’t have to wait for somebody to isolate the virus, they didn’t have to wait to grow it up, they didn’t have to try to attenuate it.”
“They were able to just take that sequence, pop it into their platform and get started making the vaccine, and start researching it,” Rasmussen said. She called platforms “the wave of the future in terms of our being able to rapidly start scaling up and manufacturing and testing vaccines.”
Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, has compared platforms to the chassis of a car. “You could build a chassis for the vaccine, and you would have it on the shelf,” Fauci said in 2016. “Then all you would need to do is insert the gene of the protein you want to express and make a gazillion doses and send it out.”
Once biotechnology companies and researchers develop the platform, it can be adapted across several different virus families. The platform from Oxford and AstraZeneca, for instance, is based on an engineered chimpanzee adenovirus, a type of respiratory virus, now being customized for SARS-CoV-2. Other companies use RNA and DNA platforms.
“We keep trying to develop a vaccine for one thing—usually the last [big virus]—and it’s a waste of time,” Fauci said. “Every time we get hit, it is always something we didn’t expect. So, instead of predetermining what it is you’re going to prepare for, make universal platforms.”
But there are some obstacles these platforms need to clear. First of all: They need to work. “The challenges are basically that you have to develop the platforms, right? And they have to be good,” CEPI’s Dr. Nicole Lurie told me.
So far in the platform class of vaccines, only Merck’s Ebola vaccine and Sanofi’s dengue vaccine have been approved by the U.S. Food and Drug Administration, and Johnson & Johnson’s Ebola vaccine is in use. But most platforms “are not yet licenced with no proof of long-term efficacy and reactogenicity,” Dr. Vipul Chowdhary, an analyst at the thinktank Policy Cures Research, told me. It can also be difficult to administer some of the platform vaccines, especially those based on DNA, Chowdhary said. Traditional vaccines are often less complicated and proven to be effective, so they still play a role in vaccine development, he said.
It’s in the specific context of a pandemic like the current one, Chowdhary said, where platform vaccines theoretically have the competitive edge. Amesh Adalja, a senior scholar at the Johns Hopkins University Center for Health Security, agreed. “They may be one of the solutions to emerging infectious disease vaccines, which have been one of the hardest tasks to solve when it comes to pandemic preparedness,” he told me. “Moving away from ‘one bug, one drug’—‘one bug, one vaccine,’ basically—you’re saying you have one platform or one technology that can be adapted to many different types of approaches,” he said. That platform could be used for anything, even outside of infectious diseases, like Moderna’s work on cancer-related vaccines.
The speed at which the platforms can be scaled up is key. “Sixteen weeks was the original goal, from the time you have the sequence to the time you are in phase one,” Lurie said. “We want to be able to go fast. That’s the whole point of trying to work really fast in a pandemic.” However, she said, new platforms “require a little more regulatory oversight.”
Safety is one of these experts’ foremost concerns when it comes to new vaccines’ potential to fight the Covid-19 pandemic—safety and politics. If a vaccine works safely in the short-term, Rasmussen said, it will likely be distributed while long-term trials are still underway. “If there are indications that any of these vaccines are at least 50 percent protective, then they’ll probably approve it and probably continue following the people in the trial so that they’re gathering that durability data at the same time as people are starting to get vaccinated,” she said. But there could be longer-term side effects that haven’t yet been observed, especially if they only occur in a small group of people. That being said, the trials have been designed to make sure the vaccines work with limited side effects before they are administered to larger groups of people, as long as the trials are allowed to continue without interference. “What I’m very concerned about is that there will be political pressure to approve a vaccine prior to having that type of safety and efficacy data,” Rasmussen said. Last week, for example, President Trump said he was “optimistic” that a vaccine would materialize by Election Day—something experts think is impossible given where trials stand at present.
A compressed timeline could obscure a vaccine’s side effects, or it could obscure the fact that a given vaccine simply doesn’t work—leading those who were immunized to believe they’re protected when they’re not. If that happens, Rasmussen said, “That’s going to really erode people’s trust in the entire process. And then we’re going to be in really bad shape…. If people don’t trust the process, if you don’t trust the vaccines, more and more people are not going to get the vaccines, and then we will really have no hope of ever being without the coronavirus circulating among us.”
We got lucky in 2009 with the swine flu pandemic. Rules and procedures were already in place for creating an updated flu vaccine quickly; vaccines for completely new viruses can take a decade or more to create and move through the approval process. The 2009 outbreak also wasn’t as deadly as feared, so those who contracted the flu before the vaccine was ready did relatively well.
In addition to being a challenge on its own, Rasmussen said, this pandemic is also “a good test to see how rapidly we could make a vaccine for a hypothetical emerging pathogen in the future.” As frightening as it may be to contemplate, SARS-CoV-2 will not be the last viral outbreak: New viruses will emerge in the future, and old viruses may emerge in new places. In the past twenty years, we’ve encountered three novel coronaviruses, and pathogens like Ebola and Zika have resurfaced in new places, often with lethal consequences. Therein lies researchers’ main hope: That the platform vaccine research currently being thrown at the coronavirus could make things much, much easier in the future.
Universal vaccines, such as a vaccine that works against all coronaviruses or all SARS-like viruses, are something of a holy grail in vaccine development. To go back to Fauci’s chassis analogy, Rasmussen said, “You’ve got a single chassis and instead of making a whole bunch of different Chrysler models on that chassis, you’re gonna make just like a Smart Car.”
Universal vaccines as pandemic prevention has long been Fauci’s dream. In a meeting with me and several graduate writing students last year, he said—presciently, in hindsight—that he suspected a new respiratory virus like influenza would cause the next pandemic, and a universal vaccine was probably the only thing that could stop it. “You can’t be prepared for the abrupt emergence of a pandemic unless you do what we have been trying to do for the last few years and we’re actually making some significant progress on: developing what’s called the universal influenza vaccine,” Fauci said. “Until we do get a universal influenza vaccine, we will never be completely prepared for a pandemic.”
The next pandemic did indeed turn out to be a respiratory virus, albeit not influenza. But it’s a pandemic that, if researchers get lucky and politicians refrain from pushing for too much too soon, could lead to breakthroughs on vaccines for both.