COVID Transmissions for 1-27-2021

The Pfizer vaccine is working in the wild

Good morning and welcome to COVID Transmissions. I hope you all had a nice weekend!

It has been 436 days since the first documented human case of COVID-19.

We’re starting to get some early real-world vaccine results, and it’s looking good. On the other hand, there were some recent vaccine development failures that i’ll also be telling you about.

As usual, bolded terms are linked to the running newsletter glossary.

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Now, let’s talk COVID.

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Out of 128,600 Israelis who received their second shot of the Pfizer vaccine, only 20 got cases of COVID-19

This has been widely reported, but by one week after the administration of the second dose of the Pfizer-BioNTech vaccine, in a population of 128,600 Israelis, there were only 20 cases of COVID-19. That’s a morbidity rate of around 0.015%.

What you should be asking yourselves right now is how this compares to patients who didn’t get the vaccine. Thankfully, we have that information, or something close to it. The morbidity rate in the general population was about 0.65%.

That’s something like 43 times higher.

This is the first confirmation we’ve had, in the wild and not in a clinical trial, that these vaccines can really do something. Very good news.

Here’s the story from The Times of Israel: https://www.timesofisrael.com/week-after-2nd-pfizer-vaccine-shot-only-20-of-128000-israelis-get-covid/

Two Merck COVID-19 vaccine candidates fail

Merck, a company known for its incredible track record in vaccine development, has discontinued its COVID-19 vaccine development program after two candidates failed in early development.

This is not great news. The more vaccines that we have, the more manufacturers we have, and the more doses we can make. It is going to take longer to vaccinate 7.8 billion people with one less company making vaccines.

On the other hand, this illustrates how fantastically lucky we are to have discovered 3—and potentially almost 4—vaccines that work for this. The vaccines that were developed first were fantastically effective. That is an amazing stroke of luck and it likely saved a tremendous number of lives.

You can read about the Merck program here: https://www.cbsnews.com/news/merck-ends-study-of-two-potential-covid-19-vaccines-following-inferior-results-in-early-testing/

Merck will be refocusing its COVID-19 program on therapeutics instead of vaccines.

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What am I doing to cope with the pandemic? This:

NYC Restaurant Week?

Restaurant week is a concept that doesn’t seem to take well to pandemic times. Except, they’re doing it anyway! With takeout. The same concept of prix fixe menus, just picked up or delivered. We’re trying out some places to be supportive, and at $20.21 per meal it’s not a bad price. Plus, it helps keep local small businesses afloat.

I’m not sure if this is happening in other cities too, but if it is, go for it!

And, for the record, I do not have any financial relationship with the folks who manage Restaurant Week.

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Carl Fink had a comment on RNA synthesis vs other vaccine manufacturing processes:

You knew I'd comment, right?

"This is a strength of the RNA platform; it’s relatively easy to edit the sequence and generate a new vaccine that responds to mutations in the virus." Can you perhaps say: is it easier to update the genetic material in an mRNA vaccine, vs. an adenovirus-carrier vaccine like the AstraZeneca one now in use in other countries[1] (and others from Russia and China)? In either case you're using well-known techniques to create a nucleic acid sequence and then putting it in some kind of carrier or coating that gets it inside mammalian cells.

Would it be harder for Novavax (whose vaccine is the spike protein, created outside the body in moth cell cultures) to create a strain of moth cells that pump out a slightly different protein? (Because I nitpick myself: Novavax's vaccine is spike proteins attached to a stabilizer that isn't defined clearly in press coverage and is probably proprietary, and accompanied by adjuvant.)

I had a feeling I’d get this comment. Here’s my reply:

Of course I knew you'd comment :)

I think really it boils down to the fact that protein synthesis is slower and relies on recombinant genetics and bioreactors to be conducted at scale. RNA synthesis is a chemical process that doesn't need to be redesigned every time the molecule to be synthesized needs to be modified.

Protein synthesis is not this way. While systems like the baculovirus expression platform allow for protein synthesis in a more predictable way than older systems, it is still a complex process involving living cells. There are serious process development investments that have to be made when a change is needed. Proteins just don't synthesize consistently, even with small changes. You really never know what's going to happen when you embark on a new protein synthesis project. It's full of surprises.

RNA synthesis can be done by a chemical process, and is more predictable. I'm sure it has its quirks too, but it's not as finicky.

So in general, if you're making some kind of macrostructure like a protein or a viral vector that involves tissue culture growth, it's going to be harder to retool your process than if you're doing chemical synthesis to make a different RNA sequence.

You might have some questions or comments! Send them in. As several folks have figured out, you can also email me if you have a comment that you don’t want to share with the whole group.

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Part of science is identifying and correcting errors. If you find a mistake, please tell me about it.

Though I can’t correct the emailed version after it has been sent, I do update the online post of the newsletter every time a mistake is brought to my attention.

No corrections since last issue.

See you all next time.

Always,

JS