Vaccine Roundup, Late December

 By Derek Lowe 

There’s been a lot of news, so it’s time to survey the vaccine landscape. For this post, I’m only going to cover the big players that are either deep into human trials or have actually been rolling out vaccines to the general population – another post to come will go further down the list. But that still leaves us with plenty to talk about. The situation is. . .well, I’m going with “chaotic”, overused though it is.

I don’t have separate categories for the Pfizer/BioNTech and Moderna vaccines this time, since they’re already under EUA here in the US and people are being vaccinated as we speak. That rollout is worth a longer discussion, but it’s as much politics as it is medicine. Vice President Pence’s statement earlier this month of having 20 million people vaccinated by the end of the year is totally out of reach, though, and I believe that he has now altered that to having 20 million doses shipped (and I’m not even sure about that). The CDC says that vaccinated numbers should start rising steeply, and I certainly hope that’s the case.

Oxford/AstraZeneca: As the world knows, this adenovirus vector vaccine has been a messy one. I think that both partners need to take responsibility for some real mistakes in the trial execution and further mistakes in their announcements since the data became available. But I haven’t seen any sign of that (although I would be even happier than usual to be corrected on that point).

Last night, the UK authorities approved this vaccine for distribution there. Of special interest is the intent to give as many people as possible a first shot, without holding back supplies for the second round. I think that this is simultaneously the correct decision for them to make and also very bad news. It appears that the coronavirus variant first reported there is indeed more contagious: Trevor Bedford is convinced, and we have early data that would seem to only make sense if the R for this form is indeed higher. One mechanism for that may be higher viral load developing in patients more quickly, making them presumably more infectious (via shedding more viral particles). That said, it also appears (so far) that the course of disease with this variant is not actually worse than the other strains, but it’s not any better, either. And with higher transmission, that’s bad enough. (Note that the WHO believes that the South Africa variant is spreading quickly as well).

That situation in the UK appears to be one of the biggest factors driving the approval and rollout, and I see their point: this vaccine is indeed better than nothing, one shot for more people is likely to be better than two-shots-for-some, and it looks like they’re going to need all the help they can get. But “better than nothing” is a rough place to be. So what do we know about the efficacy of a single shot of the Oxford/AZ vaccine, and about the effect of waiting for a second one?

All I can say is that attempts to answer those questions land you immediately in a confusing mess. It’s a mess made worse by AstraZeneca, whose CEO has made statements about the vaccine’s efficacy that are not (so far) backed up by actual numbers. If you’d like me to name a major drug company that’s going to come out of this pandemic looking worse, it’s them. Anyway, as you’ll recall, initially there was a hint that a lower first dose followed by a standard second dose might be more protective overall (although I don’t think the evidence for that is very strong at all, considering the statistical spread in the data). But now there’s a report that increased efficacy might be driven by an even longer wait between the two doses. I don’t find that evidence very compelling, either (we’re getting into some pretty small subgroups by this point, and that is always a dangerous area to draw conclusions from). And if you’re going to leave people walking around with a half dose at first, or a full dose but with a longer wait for the second one, it makes the question above even more crucial: how protective is one dose?

We do not know. We don’t know for this vaccine, nor for the Pfizer/BioNTech one, nor for Moderna’s. No studies have been designed to find that out, so all we can do is guess based on what we’ve seen with the interval between doses in the two-dose studies. That’s been encouraging with the two mRNA vaccines, but remember: we don’t know how they are over a longer period, because no one was left without a second dose for that long. It’s certainly possible that without the second booster that the protection seen after one shot starts to wane. We do not know. And we know even less about the Oxford/AZ vaccine’s behavior under these conditions. Giving as many people in the UK as possible a single dose of that vaccine with a longer wait until the booster is a gamble, and you wouldn’t want to do it that way if the alternatives weren’t even worse. It’s the right move, unfortunately, and it’s a damned shame it’s come to this.

The US trial of this vaccine was paused for weeks, of course, while adverse events were investigated. It’s basically fully enrolled now, and the data will include many more elderly patients than have been investigated to date. I would assume that our current terrible infection rates will allow this trial to move along rather quickly, but I have no estimate of when we might see it report.

J&J: data on the one-dose clinical trial of this adenovirus vector candidate should be coming very soon indeed. It’s going to be of great interest, given the results from the Oxford/AZ effort, and given the deliberate one-dose protocol. The company has a two-dose trial underway as well, but we won’t be seeing data on that one until later.

CanSino: this adenovirus vector vaccine (Ad5) is said to be submitting data to Mexico shortly, presumably for regulatory approval. Trials have been underway there, as well as in Pakistan, Chile, and other countries. No efficacy or safety data have been reported publicly, however.

Gamaleya Research Institute: this two-adenovirus-vector two-dose vaccine has made some news as well. Earlier this month, a press release from the GRI said that the vaccine was 91% effective, based on a trial with over 17,000 vaccinated patients and over 5600 controls. The release also says that a full paper is in the works, to be published in a leading journal, and I very much look forward to that. It appears that the vaccine is now being shipped to Belarus, Argentina and Hungary, but Reuters reports that the Argentina shipment is for only the first dose, which is the easier of the two different adenovirus vectors to manufacture. Nothing on the other countries as yet, but the Hungarian shipment was quite small (6,000 doses), which tells you that it’s more in press-release territory anyway. It’s unclear what’s going on – Reuters had a source saying that the Argentine shipment was excess production from the manufacture of the first shot, and that they’re still catching up on the second. I have seen no reliable figures on the protection offered by just that first shot – the director of the GRI has said, though, that immunity from the first shot lasts only 3 to 4 months.

Meanwhile, the earlier reported collaboration between GRI and AstraZeneca seems to be real – a clinical trial has been registered. I’m quite curious to see how this is going to go, and whether it will produce results in time to make any sort of impact.

Sinovac: Word has just come in the last couple of days from a trial in Turkey of this inactivated virus vaccine. Turkish officials said that it was 91% effective, but we have no numbers to back that up yet. What we do know is that this was based on a rather small trial (752 people vaccinated, 570 in the control group), so the confidence interval on that number is surely going to be large. Sinovac, for its part, seems to have said nothing yet. I’m glad to see that this vaccine seems to be working, but you would really want to see a lot more data on both efficacy and safety.

SinoPharm/Beijing Institute: this inactivated-virus vaccine candidate has just reported data in The Lancet from its Phase 1/2 trials (safety and immunogenicity). And they have now announced that interim analysis of Phase 3 data show 79% efficacy, but with no actual numbers yet. Note that this is the same one that UAE officials announced an 86% efficacy for, but (as far as I can see) SinoPharm has still made no comment on that. Everyone would very much like to have a more complete look at the data, but there is no word on when that will be forthcoming. We don’t know how many people were in these trials, the inclusion or diagnostic criteria used, nor do we have any safety data at all. So this could be encouraging, but I myself would rather stay home and wait for something with more numbers behind it, rather than take a vaccine on this basis. More on this as more data appear.

Novavax: this should be the next trial we hear about after J&J reports, and a lot of people are waiting to see how this recombinant-protein candidate works out. These will be results from a trial in the UK – a US Phase 3 just launched this week. This one has much less rigorous storage requirements and is generally easier to manufacture, and it could be a big contributor if things work out.

https://blogs.sciencemag.org/pipeline/archives/2020/12/30/vaccine-roundup-late-december