A scientist in a mask holds up a container of tubes

An engineer works on an experimental vaccine for COVID-19 at the Sinovac Biotech facilities in Beijing on Wednesday.

Nicolas Asfouri/AFP via Getty Images

Slate is making its coronavirus coverage free for all readers. Subscribe to support our journalism. Start your free trial.

I have a vague timeline in my head: I know better than to think that life will return to normal once my state’s shelter-in-place order is lifted. I have been trying, instead, to think about “when life will return to normal” as being connected to a different milestone—the creation of a vaccine, which will stop us from getting sick in the first place. Maybe you have been thinking about this too. If you have, the timeline you are probably working with is “12 to 18 months,” maybe edging into two years. “We are talking at least a year,” Michael Ryan, executive director of the World Health Organization’s health emergencies program, said in March. “It will take at least a year to a year in a half to have a vaccine we can use,” Anthony Fauci, director of the National Institute of Allergy and Infectious Disease, said, also in March. “The reality is, it will take over a year in my expectation to really find a new vaccine,” a pharma CEO told the press back in January.

“The thing to note with the timeline is people often caveat it with a statement, ‘if everything goes perfectly.’ 

— Matthew Watson

That timeline feels … long. And, though we might be able to get back to some kind of normalcy with the help of testing and therapies, it’s actually on the shorter side of when we will get a vaccine. “Everybody would love to say yes, we can achieve an 18-month vaccine turnaround—but it’s a goal,” says Maria Elena Bottazzi, a virologist at Baylor who is working on a couple possible vaccines against COVID-19. “If you look historically, we’ve never been able to develop a vaccine with that timeline.” Ebola’s vaccine, for example, took five years to develop, following the 2014 outbreak; a more typical timeline is 10 years. “We’re trying to break a record here—maybe it’s not going to be four or five [years], maybe it’s three, maybe it’s two, maybe indeed it’s 18 months,” Bottazzi says. In other words, the phrasing that has become almost boilerplate is maybe not quite as reliably correct as you (and I) might wish it were.

There are more than 70 COVID-19 vaccine efforts globally, at least; with so many, it’s reasonable to be optimistic that we will have a vaccine in some kind of record time frame. There are even a few that are posed to break the record: one from a company called Moderna that began trials in humans in March (this is the one that Fauci is referring to in his estimates), one from a group at Oxford that claims it could even have doses available by fall. Yes, it says it might even have some doses by the fall.

“The thing to note with the timeline is people often caveat it with a statement, ‘if everything goes perfectly,’ ” says Matthew Watson, an analyst at the Johns Hopkins Center for Health Security. “I think that’s really important to pay attention to. Things rarely go perfectly.”

It’s easy to skim past those words on a page, though, so I’ve unpacked what they’re referencing. Here’s what could go wrong, because it has before.

There’s Not Enough Money

It seems like this should be a nonproblem, with governments, philanthropic organizations, and drug companies realizing their efforts behind vaccinating against the coronavirus might be the most pressing concern of our time. But money has already hampered our timeline for getting a vaccine for a novel coronavirus, perhaps significantly. The reason we don’t have a vaccine for SARS, or MERS, close cousins of the novel coronavirus, is because the outbreaks and accompanying funds stopped before researchers could develop a vaccine. Bottazzi and her collaborators have samples of a SARS vaccine stored in a freezer in Texas, a vaccine that could possibly offer some meaningful protection against the novel coronavirus now. It’s possible that if they’d had the funds to take that SARS vaccine through clinical trials, we literally would have had a viable vaccine against the new coronavirus … yesterday.

Obviously, now that there’s money available, they’re picking up work on that vaccine again. But it’s not an instantaneous process to get funding. “We still don’t have it all,” says Bottazzi, who, when we spoke in late April, was still waiting to start testing the SARS vaccine in humans. “We cannot start a clinical trial ‘a little bit.’ You have to have all the funding.” That means convincing agencies handing out funding that your vaccine is one of the right ones to invest in by writing grants.

The mechanics of securing funding still slow individual projects. But the coronavirus is such a huge problem now that funding overall is perhaps one of the smallest hurdles, and somewhat irrelevant to the current optimistic timeline, at least for a first vaccine. But money has been a problem already, and it could be a problem down the line.

The Vaccine Fails Safety and Efficacy Tests

This is the actual science portion of getting a vaccine to market. As Fauci put it at a March 26 briefing, safety is just as important as efficacy: “The worst possible thing you could do is vaccinate someone to prevent infection and actually make them worse.” And “until you do the clinical studies, there’s no assurance that any vaccine will work,” says Bottazzi. “Vaccines often fail,” says Nancy Connell, a researcher at the Johns Hopkins Center for Health Security. “That’s why the world community is pushing several vaccines forward at once.”

Typically, a vaccine is developed in a lab, then injected in animals to see if it’s effective, then into a small group of a few dozen healthy people to test for adverse reactions, then into a larger group of a few hundred people, and then in thousands of subjects. Researchers are speeding things up by starting clinical trials (for safety) as animal testing (for effectiveness) is still underway, or quickly moving to test out vaccines on a larger group of human test subjects.

This is … good and also bad. “It’s reassuring and concerning how quickly vaccine development is happening,” Timothy Lahey, an ethicist and vaccine researcher at the University of Vermont Medical Center, told Slate’s What Next TBD. The faster you push a vaccine into larger groups, the higher the risk of some rare side effect popping up, which is a good reason for the process to take so long, typically. But our circumstances are currently extraordinary. “We are not comparing [rapid vaccine development with] doing nothing and everyone is safe and fine,” says Thomas Bock, co-founder of Apandemic, a group of industry folks and scientists working on therapies and vaccines. “We really are comparing people dying with the risk of potential side effects.”

Even promising early data aren’t much assurance that a vaccine will make it through the full gamut of trials. Vaccines use antigens—the spike part on the outside of the novel coronavirus— to prod the body into producing an immune response. Traditional vaccines do this by putting a little bit of dead or hampered virus into the body; RNA and DNA vaccines basically hand bodies some instructions to make the antigens themselves. Because the body does some of the work, the vaccines can be faster to tweak and produce for clinical trials. But also, none of them have ever made it to market. It’s hard to say why, says Bottazzi, who is working on classic approaches herself: “It might be that they’re not giving the right responses. I don’t know, because when these technologies are advanced by for-profit entities, you don’t see the negative data. We don’t see where the bottlenecks are.” At any rate, one key thing to keep in mind: One of the early candidates, from Moderna, is an RNA vaccine.

We Don’t Have Enough Doses

Getting a vaccine that works is only one part of the battle. “After the clinical trials are over, now comes the big problem of making a hundred million, several hundred million, or a billion doses,” says Connell. Yes, everyone in the world is (probably) going to want this vaccine.

Getting a vaccine that works is only one part of the battle.

One way companies like Moderna are getting ahead is by ramping up production of doses before clinical trials are completed. “Even before you know something works, at risk, you have to start producing it,” said Fauci in the March press conference. That didn’t happen with the Zika vaccine, which, according to Fauci, was a mistake. (Hopeful estimates gave a Zika vaccine a timeline of less than two years from when WHO declared Zika an international public health emergency in February 2016, but cases slowed before human trials were finished. Though having one could still save lives, there’s no Zika vaccine on the market. Yes, we do this all the time, it turns out.)

Producing so many doses will require creating new facilities or commandeering those used for other vaccines. Critics of RNA and DNA vaccines point to the fact that we already have the established infrastructure to make traditional vaccines. “Governments are trying to build potential manufacturing capacities for [RNA and DNA vaccines], but they are not there yet,” says Thomas Lingelbach, the CEO of Valneva, which is working on a traditional approach to a COVID-19 vaccine. Not that it’s easy to just start producing any vaccine by the billions. He plans on using a facility that was intended for Valneva’s chikungunya vaccine, whether for Valneva’s vaccine or perhaps another company’s if Valneva’s is unsuccessful. “These are complicated biological processes, no matter what technology you use,” says Lingelbach. It’s a manual process too, featuring human beings in safety gear. “It’s not like producing a car,” he says.

Supply shortages like those that have plagued other steps of the coronavirus response—reagents for tests, protective gear for hospital workers—could be an issue during vaccine manufacturing too. A simple chemical supply chain issue hampered production of the swine flu vaccine in 2009, leaving cities with far fewer doses than residents, during a national emergency.

People Can’t Access the Doses We Do Have

Yes, there’s the possibility that anti-vaxxers will not accept the necessity of a vaccine, especially one that has been sped through development, for themselves or their children. Or maybe not. One saving grace of this current situation: It can be hard to see the point of a vaccine for a disease that is no longer an issue, like measles, because it has been kept at bay by vaccines. The novel coronavirus is still, clearly, an issue. Plus, not everyone needs to get the vaccine for it to be effective—just about 70 percent of the population does, thanks to herd immunity.

Anti-vaxxers get a lot of attention, but there are other factors we should be concerned about when it comes to getting people to actually receive vaccines—namely, health care inequality, both in the States and abroad, as Dan Engber explained last year in Slate. It might not be hard to imagine going to your local CVS to get a COVID-19 vaccine. But this is easier to do if you have insurance, live in an area with easy access to health care services, and have the ability to take paid time off from work for an appointment. A Reuters story on measles notes that parents in Madagascar might walk for miles to get a vaccine, which can in turn cost many times a family’s daily budget.

Researchers are already thinking about how mass vaccination could go faster, through delivery methods that do not require a trained clinician to handle an injection. At the University of Pittsburgh, for example, researchers are working on a vaccine that comes in a Band-Aid-like patch, covered in hundreds of tiny painless microneedles (similar to a delivery mechanism already used in acne treatments). In a future coronavirus season, your vaccine could be handed over a drugstore counter or arrive in a slim padded envelope in the mail.

We Drop the Ball in the Long Haul

It’s very possible that we’ll need a few vaccines to get us through this pandemic. Maybe an early vaccine is only somewhat effective, or can only be produced in small quantities or only in a handful of countries. Having more than one will help fill the gaps left by the first. And then we might need updated versions of the vaccine year after year, the way we do for flu as the virus mutates.

We face a future where outbreaks from diseases jumping from animals could be more common, and some researchers are already worried about problems beyond making it past this one single finish line. “What’s going to be the real business model that’s going to allow for sustainable funding, not only for coronaviruses, but for the whole ecosystem infectious diseases?” says Bottazzi. “It’s not like after 18 months we have a vaccine and that’s it, all the work stops. It’s forever.”

Source link