Was the Covid vaccine actually too slow? Can we be faster next time? (Yes)

Terrific, terrific piece on vaccines from David Wallace-Wells.  Due to the years and years of research on vaccine platforms and coronaviruses and, Moderna basically had the vaccine just about to get approved in January.  So, why are we still waiting?  Because, of course, we want to be sure and, you know… first do no harm.  But a lot of interesting questions are raised in thinking through these issues.  

Could things have moved faster from design to deployment? Given the grim prospects for winter, it is tempting to wonder. Perhaps, in the future, we will. But given existing vaccine infrastructure, probably not. Already, as Baylor’s Peter Hotez pointed out to me, “Operation Warp Speed” meant running clinical trials simultaneously rather than sequentially, manufacturing the vaccine at the same time, and authorizing the vaccine under “emergency use” in December based only on preliminary data that doesn’t track the long-term durability of protection or even measure the vaccine’s effect on transmission (only how much it protects against disease). And as Georgetown virologist Angela Rasmussen told me, the name itself may have needlessly risked the trust of Americans already concerned about the safety of this, or any, vaccine. Indeed, it would have been difficult in May to find a single credentialed epidemiologist, vaccine researcher, or public-health official recommending a rapid vaccine rollout — though, it’s worth noting, as early as July the MIT Technology Review reported that a group of 70 scientists in the orbit of Harvard and MIT, including “celebrity geneticist” George Church, were taking a totally DIY nasal-spray vaccine, never even intended to be tested, and developed by a personal genomics entrepreneur named Preston Estep (also the author of a self-help-slash-life-extension book called The Mindspan Diet). China began administering a vaccine to its military in June. Russia approved its version in August. And while most American scientists worried about the speed of those rollouts, and the risks they implied, our approach to the pandemic here raises questions, too, about the strange, complicated, often contradictory ways we approach matters of risk and uncertainty during a pandemic — and how, perhaps, we might think about doing things differently next time. That a vaccine was available for the entire brutal duration may be, to future generations trying to draw lessons from our death and suffering, the most tragic, and ironic, feature of this plague…

In weighing other risks and uncertainties, Americans have been much less cautious,and not just in the case of marching maskless into Wal-Marts. On March 28, on what would normally be considered very thin evidentiary ground, the FDA issued an emergency-use authorization for the drug hydroxychloroquine. On May 1, it issued an EUA for remdesevir. On August 23, it issued another for convalescent plasma (the practice of injecting antibodies from the blood of recovered patients into those sick with the disease). These were all speculative authorizations — gambles, without concrete evidence, that existing treatments which scientists and doctors had some reason to suspect might help with the treatment of COVID-19 would be both safe and effective. All of these bets were lost. None of them, in the end, proved effective. 

Of course, none of those would ever be used on anything close to the scale of the vaccine.  Still, a very different weighing of risks.

Arguably, what we should really learn from this to expedite future vaccines is to, essentially, skip phase I because we’ve already done the vaccine safety groundwork:

None of the scientists I spoke to for this story were at all surprised by either outcome — all said they expected the vaccines were safe and effective all along. Which has made a number of them wonder whether, in the future, at least, we might find a way to do things differently — without even thinking in terms of trade-offs. Rethinking our approach to vaccine development, they told me, could mean moving faster without moving any more recklessly. A layperson might look at the 2020 timelines and question whether, in the case of an onrushing pandemic, a lengthy Phase III trial — which tests for efficacy — is necessary. But the scientists I spoke to about the way this pandemic may reshape future vaccine development were more focused on how to accelerate or skip Phase I, which tests for safety. More precisely, they thought it would be possible to do all the research, development, preclinical testing, and Phase I trials for new viral pandemics before those new viruses had even emerged — to have those vaccines sitting on the shelf and ready to go when they did. They also thought it was possible to do this for nearly the entire universe of potential future viral pandemics — at least 90 percent of them, one of them told me, and likely more…

As Hotez explained to me, the major reason this vaccine timeline has shrunk is that much of the research and preclinical animal testing was done in the aftermath of the 2003 SARS pandemic (that is, for instance, how we knew to target the spike protein). This would be the model.Scientists have a very clear sense of which virus families have pandemic potential, and given the resemblance of those viruses, can develop not only vaccines for all of them but also ones that could easily be tweaked to respond to new variants within those families.

“We do this every year for influenza,” Rasmussen says. “We don’t know which influenza viruses are going to be circulating, so we make our best guess. And then we formulate that into a vaccine using essentially the same technology platform that all the other influenza vaccines are based on.” The whole process takes a few months, and utilizes a “platform” that we already know is basically safe. With enough funding, you could do the same for viral pandemics, and indeed conduct Phase I trials for the entire set of possible future outbreaks before any of them made themselves known to the public. In the case of a pandemic produced by a new strain in these families, you might want to do some limited additional safety testing, but because the most consequential adverse effects take place in the days right after the vaccine is given, that additional diligence could be almost immediate.

If we’re smart, there’s a pretty clear long-term lesson we can learn to help us so much for the next time.  I fear we’re not remotely smart enough, but, just maybe…

According to Florian Krammer, a vaccine scientist at Mount Sinai, you could do all of this at a cost of about $20 million to $30 million per vaccine and, ideally, would do so for between 50 and 100 different viruses — enough, he says, to functionally cover all the phylogenies that could give rise to pandemic strains in the future. (“It’s extremely unlikely that there is something out there that doesn’t belong to one of the known families, that would have been flying under the radar,” he says. “I wouldn’t be worried about that.”) In total, he estimates, the research and clinical trials necessary to do this would cost between $1 billion and $3 billion. So far this year, the U.S. government has spent more than $4 trillion on pandemic relief. Functionally, it’s a drop in the bucket, though Krammer predicts our attention, and the funding, will move on once this pandemic is behind us, leaving us no more prepared for the next one. When he compares the cost of such a project to the Pentagon’s F-35 — you could build vaccines for five potential pandemics for the cost of a single plane, and vaccines for all of them for a fraction of the cost of that fighter-jet program as a whole — he isn’t signaling confidence it will happen, but the opposite.

Actually, I have no doubt Joe Biden and Democrats in Congress would be willing to allocate the funding to this and make it a priority.  Whether we can get the necessary Republican on board, alas, is very much an open question.  Anyway, though, this is a hell of a road map.  Let’s hope we’re smart enough as a society to take it.