So let’s take a few minutes to think about what happens when the vaccine trials start to read out. I’m making the assumption that the data will be freely available in a timely manner (which means before any decisions are made), because the alternative to that is Not Real Good. Another not-real-good alternative would be to declare the first one to read out the instant winner, because (as noted by Anthony Fauci) that would certainly screw up the trials of the others. But if we avoid these mistakes (no guarantees are expressed or implied), there are still a number of fairly likely things that I don’t believe the general public is quite ready for.
One of those: what if the first vaccine results aren’t very impressive? This could happen. I’m really hoping it doesn’t, but anyone in the business will tell you that you don’t know what efficacy is really going to be like until you run an efficacy trial, and that goes for vaccines as much as for anything else. I will say that the available biomarkers (antibodies and T cells) are much stronger in vaccine work than they are in many other areas, but on the other hand, it’s immunology. Which is full of fun and interesting surprises. So if the first trial to really give a solid efficacy read comes in lower/weaker than we’d all like to see, my guess is that the press and the public won’t take it too well. There will be a rush to “OMG We Can’t Make A Vaccine To Corona” takes, I think, which will sow some despair and panic. I would expect the stock market not to take the news well, either.
But even if the first results aren’t great, it doesn’t mean that we’re (necessarily) hosed. That’s the good thing about having several different vaccines going, with different platform technologies. We are really going to have to wait and see what the various approaches are going to produce, even though “wait and see” is not exactly the zeitgeist right now. We have the different adenoviruses (and other vectors, which will come later), the inactivated-virus vaccines, the mRNA candidates, the recombinant proteins – there’s no reason to think that these are all going to come out the same, and that’s going to be important to keep in mind.
To that point, here’s another possibility that’s quite possible: the Patchwork Quilt of Efficacy. What if we get a mixture of results, with Vaccine A being pretty good, but not in older patients, while Vaccine B seems better in that cohort but is harder to roll out for distribution, while Vaccine C showed more even results over various patient cohorts but is beaten by some other candidate in any particular one, while Vaccine D was strong but definitely had more adverse events. . .you see what I mean. I can easily imagine something like this happening, and the thing is, it’s not just going to drop all at once. We’re going to get those various results one after the other and will have to fit them into an unavoidably messy picture, adjusting our plans as more data points become available. Overall, I think it could be a serious mistake to declare a winning vaccine too early (unless something comes in just kicking coronavirus ass all over the field, which would frankly be fine), but telling everyone to wait while we see what the next ones bring is probably not going to go over well. There will be tremendous pressure to just start dosing people with anything that looks reasonable, and you can’t blame anyone for it.
Regarding those adverse events, I’m no immunologist, but the one that I’m worried most about is probably Guillain-Barre syndrome. Pronounce that one something like gee-YAH bur-RAY for maximum effect, but I’ve heard plenty of other more Anglicized pronunciations in the wild. No matter how you say it, GBS is an autoimmune response that leads to an attack on the myelin sheaths of the nervous system – bad news, obviously, but the good part is that most cases resolve. Not all of them do, though, and even many of the resolved ones involve spending time in a hospital in pretty serious condition. GBS happens spontaneously after some respiratory infections, for immunological reasons that are still being worked out, and is most commonly seen in younger women. It can come on after vaccination, in the same way as it can come on after infection, and it’s widely recognized as one of the big problems with the 1976 swine flu vaccine rollout, and is certainly something that vaccine developers in general keep an eye out for. We do not want to have to wrestle with this problem, but it’s a rare enough event that only the large Phase II/Phase III trials will have a chance of giving us a read on it at all. For context, the 1976 vaccine is believed to have caused one extra case of GBS per 100,000 people vaccinated – it’s the sort of thing you might well not pick up on at all until you’re going out into the broader population. “Teenager Rushed to Hospital After Coronavirus Shot” is not a headline that will do anyone any good.
That wider population is always the worry, immunologically. We all have different immune systems – that’s the point, otherwise one plague or another would have wiped us off the planet by now. The number of rare immune-linked disorders is large and various because of this, and that means that the response to any new vaccine could show some oddities as you start heading out into millions of people Tens or hundreds of millions – yeah, you would have to expect some rare and bad events to poke up, and if one of them happens with major media coverage, things could get ugly.
Even if things go well, though – and I continue to think that for at least one of the vaccine candidates they will – there are some complications. All but one of the vaccines being tested now (J&J’s is the exception) will need a booster shot some weeks after the first one. And from the antibody titers we’ve seen in the Phase I trials, you wouldn’t necessarily expect that much protection with just one shot. People are going to have to realize this: the first shot will not mean that you’re in the clear, as ready to shed your mask and hit the streets as you might be. For that matter, it’s still going to take some time after the second shot to reach protective levels, so it seems, so it’s not like even the booster will mean that you can hit the karaoke bar that evening. We will need to be ready for “I Got the Vaccine And I Got Coronavirus Anyway” reports that will turn out to be due to one of these situations. The logistics of getting everyone through a two-shot immunization course will be nontrivial, in any event.
OK, I don’t want this post to be too depressing – we need to keep our eye on the likelihood that we’re going to see an effective vaccine in the coming months. That’s going to be great, but nothing says that launching it into the world has to happen smoothly. One last point: when we launch that vaccine (or those vaccines), we are not only going to have to be transparent about why the choice was made the way it was: we’re also going to have to be transparent about who gets it first and why. Frontline medical workers, surely, and others in similar positions. People who do economically vital jobs (supply chains, etc.) whose work unavoidably puts them at higher risk. You can come up with more categories easily, but one category that I hope we avoid is People Who Know Some People. If there’s a perception that the well-connected are cutting the line, that’s not going to go over well, either, and it shouldn’t. I would recommend being completely open about the order of vaccination and trying to stick to it, visibly. Ideally, this should be publicized before we even start getting vaccine readouts, but we’ll see. . .