We have a good amount of news in the coronavirus vaccine world, so it’s time for another look over the field. My most recent overview post is here, from late December, with this one from mid-December, and about ten days ago I looked at news from J&J and SinoVac (also summarized below). I’m going to try to round up a lot of lesser-known efforts in this post as well.

Viral vector vaccines:

The big news here this morning is from Merck. They were developing two candidates in this category – with Themis they were working on a measles-based one, and the IAVI a VSV-based one. But the company announced today that they’re dropping both of them after looking at the first human Phase I data. The immunogenicity of both candidates was below the antibody levels seen in convalescent plasma, and below that seen with other reported vaccines. So that’s a good reason to bail out, sadly.

It’s not clear (of course) what led to this lower response. STAT has some interesting statements from IAVI to the effect that the intramuscular administration of the VSV vaccine may not have been the correct route. They seem to believe that different ones may be worth pursuing, especially intranasal, but they’re going to have to round up the money for that idea on their own. But this is a lesson that we have not abrogated the failure rates in drug discovery: there are still plenty of ways to go wrong, and often the only way to find them is to go into clinical trials. It has ever been thus.

There are other viral vector vaccines out there being administered, of course. The UK is pushing ahead with the Oxford/AstraZeneca adenovirus one, of course, but its true efficacy is not any more clear than it was when I last wrote about it in December. This one has been approved in Thailand, Mauritius, Ecuador, and more countries besides, but word has come recently that it will be in much shorter supply than expected due to manufacturing problems.

The CanSino adenovirus vector vaccine is being offered to several countries (such as Pakistan and Indonesia, on an emergency basis) and may be about to be approved in Russia, which I believe would be its first actual regulatory approval outside its use in China. But it’s been very hard to get a read on its actual efficacy – the data are (from what I can see) scattered and incomplete. I honestly don’t see this one being approved in many countries under these conditions.

Similarly, the Gamaleya vaccine from Russia (“Sputnik-V”) continues to be rolled out in a few countries, as I mentioned in December (the latest is emergency use in the Philippines and in the UAE. The full paper on its efficacy trial has not yet published. There’s a report that the combination trial using this one and the Oxford/AZ vaccine may start up in February.

We’re still waiting on clinical trial data from J&J, and it’s still expected any day now. The efficacy numbers on their one-dose protocol are highly anticipated, and the news this morning that Merck’s two vaccine candidates have been shelved just adds to that. Anthony Fauci said on Friday that he would be surprised if a regulatory decision were not made on this one within two weeks. Frankly, it had better work – we need it.

There are other viral vector candidates out there. ReiThera has one going in Italy, and earlier this month the company said that no safety signals had been seen in the first 100 patients in a Phase I trial. It looks like it’ll be a while before we see any efficacy data on this one – you’ll note talk in that article about Italy having “vaccine independence”, but that would involve sitting back and watching most of the rest of the world getting dosed with other candidates. Washington University has been working on a single-dose nasal viral vector candidate, which has now been licensed to Bharat Biotech in India, who say that they hope to start human trials in February. We’ll see if that goes off. Similarly, MediciNova in Japan has been working on an intranasal vaccine, but there’s been no substantial news from them for months. Beijing Wantai has another intranasal candidate – the last thing heard from them was registration of a Phase II trial in China in November. AltImmune has an intranasally-dosed vaccine in development, but in late December the company announced a clinical hold from the FDA (apparently due to manufacturing concerns?), and this has apparently not yet been lifted. Most of the articles you see about this company are about its stock rather than its science, a disconnect that also shows up with Inovio and with Vaxart. They’re another company with a viral vector candidate, this one dosed orally. But I can find no updates at all about its clinical progress – just excited talk about its prospects as an investment. Patrick Soon-Shiong’s ImmunityBio is also working on an oral adenovirus vector vaccine. A Phase I trial is said to have finished up in November, but I have seen no data from it. Further back, Lancaster University and Texas Biomedical have reported animal studies of another intranasal candidate, this one based on a poultry virus (Newcastle Disease).

Finally, there’s a small company called Gritstone that recently announced a Phase I trial of a combination two-dose regimen: one dose of an adenovirus vector and one dose of a self-amplifying RNA. So that takes us to. . .

RNA/DNA vaccines:

Well, the Moderna and Pfizer/BioNTech vaccines are now going into millions of people. The most comprehensive data set we have so far is from Israel, where a vigorous and organized vaccination campaign has been underway with the Pfizer/BioNTech vaccine. So far, so good. The data after the first shot seems to almost exactly recapitulate what was seen in the clinical trials, with a split between vaccinated and unvaccinated people emerging around Day 13 after dosing. The UAE is a country that’s well up there in percent of the population vaccinated, but they have a mixture of SinoPharm, Pfizer/BioNTech, and Gamaleya vaccines being administered, which will be interesting to watch – I hope they’ll be able to collect enough data for a comparison among all three. The Pfizer/BioNTech vaccine has been approved in Australia, and is expected to be approved soon in Japan.

Adverse effects in the US, Israel, and Europe seem to me to be low and consistent with the clinical trial data. There seems to be a headline every time there is a potential AE, which is what I basically expected, but I’m not seeing anything that sets off alarm bells yet. The CDC is monitoring reports of anaphylaxis with both vaccines, but these seem to be at the few-per-million level.

This morning came word of a study from Moderna about the antibodies raised by its vaccine and the new coronavirus variants. It looks like the B.1.1.7 variant doesn’t show much difference compared to “coronavirus classic”, but the South African variant shows about a sixfold reduction in efficacy. That’s not good news, but it’s not horrible news, either: the antibody response that’s still there is expected to be enough. But the company says that they’re working on a modified mRNA to potentially be used as a booster shot, should this be necessary, and describe this as an “insurance policy”. A manuscript on this should be showing up shortly. Update: it’s out now!

Curevac‘s mRNA candidate has gotten a boost with the announcement of a partnership with Bayer. Phase III trials are underway in Mexico; it will be very interesting to see some data from this one, given how well the other two mRNA candidates have worked out.

The other big candidate in this category is Inovio, a DNA construct vaccine that is planned to go into Phase III sometime after March. You’d have to think that the landscape will be quite different by the time this one makes it through trials – for now, we’ll wait on what the Phase II efficacy data look like when those come out. There’s a small company in Vancouver, SymVivo, with an oral DNA vaccine delivery platform – they have announced the start of a Phase I clinical trial in Australia in November, and recently signed a deal with Merck for vaccine development in general (although presumably not coronavirus ones, given today’s news). I mentioned self-amplifying RNA above – a candidate from Imperial College using this technology went into human trials back in the summer, but I have seen no word on any results yet. It does still seem to be alive, though, based on this announcement.

Inactivated virus vaccines:

In India, Bharat Biotech‘s Covaxin has been given emergency approval there while it’s still finishing up Phase III trials. The Phase I data have now appeared in The Lancet, and the results certainly seem worth watching. I wrote last month about the confusion around the SinoVac candidate, and that has not cleared up. I simply have no good idea how effective the vaccine is; the data have come out in a very disorderly fashion. The situation for the SinoPharm vaccine is not a lot better – I wrote about that one in December as well, and although it’s being shipped to more countries now (such as Egypt), to the best of my knowledge no Phase III data set has been released.

Recombinant protein vaccines:

We’re still waiting on Novavax Phase II data; that’s the most highly anticipated trial readout now behind the J&J one. The NIH/BARDA-funded Phase III started up just before the first of the year; the company’s own Phase 3 trial in the UK started in September. There have been reports that the expected trial difficulties with the availability of other approved vaccines have affected the patient numbers. This candidate is given with the company’s own proprietary adjuvant. Medigen of Taiwan has announced that they’re now dosing patients in Phase II (with an adjuvant from Dynavax). There’s a recombinant subunit vaccine from Baylor, again with a Dynavax adjuvant, that’s now in trials in India with Biological E. Limited of Hyderabad. Meanwhile, I wrote last month about the setbacks in the GSK/Sanofi effort; there’s been no update on their retooling since then.

You’ll notice the constant mention of adjuvants – the recombinant proteins really need that to get a strong immune response (see this mouse study for a vivid example). But there are plenty of good ones around, and no one (from what I can see) is being so bold as to try to go ahead without one.


I’m sure I’ve missed some candidates as well – there’s a lot of work going on from various organizations, and if some of the major efforts stumble (as Merck did today), they could rise up the charts. I’ll update this post as people send me news over the next few days!

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