The Pieces Of The COVID-19 Vaccine Puzzle Start To Fit Together

Another vaccine maker this morning reports encouraging test results. Moderna’s vaccine, like Pfizer’s, is a type that’s never been used before. So what does that mean exactly?

The pharmaceutical company, Moderna, announcing Monday its Coronavirus vaccine appears to be successful enough to move ahead, and will get ready to apply for Emergency Use Authorization from the FDA as soon as safety data is complete, “in the coming weeks.” It says an initial analysis of safety data “did not report any significant safety concerns”. With the most common side effects being fatigue and muscle ache. The company has not yet submitted its results to be peer-reviewed.

Moderna says during its trial of 30,000 participants in the U.S., it identified 95 of them who became infected with COVID-19, 11 severely. Of those infected, only 5 had actually received the vaccine and 90 had received a placebo. Meaning at least among that limited group, the vaccine appeared to be 94.5% effective. Pfizer reported an initial effectiveness rate of more than 90%. If those numbers bear out, they both exceed the level of effectiveness the FDA had previously suggested it would require in order to approve a vaccine’s emergency distribution. By a lot.

Both vaccines require shipment at low temperatures, which could prove a challenge logistically. Moderna’s doesn’t need to be quite as low. And the company issued a 2nd news release saying their vaccine’s shelf life is longer than they initially thought.

The main challenges for bringing a vaccine to the public (we paraphrase from a Tweet by Pfizer) are these:

  • Is the vaccine safe?
  • Does it work?
  • Can it be manufactured and distributed effectively?

So much of the coverage so far is focused on safety. Which is important given that the vaccine development and approval is being highly accelerated. With the FDA asking for 2-months of safety data before it’ll consider approving a vaccine. That means tracking participants enrolled in experimental studies for 2-months after they received the final dose of the vaccine. (President Trump called that guideline a “political hit job“.) Usually, the FDA requires a couple of years of safety data. Both these COVID-19 vaccines require 2 doses.

But the announcements from Pfizer and now Moderna that have created all the sudden excitement aren’t primarily about safety. Because the safety data is not yet complete.

They’re about whether the vaccine actually works.

And in order to prove the vaccine works, a significant number of people in the trials have to get sick. That’s because in order to infer the vaccine itself actually works, there’s got to be evidence people enrolled in the trial were actually exposed to the virus. And the way this is done is by measuring how people in the clinical trials who actually get the vaccine do compared to those who got a placebo.

Demonstrating safety in terms of no harmful side-effects, etc. can most of the time be mapped out on a timeline. And then you just have to adjust for some stalls and setbacks, which have happened.

Showing a vaccine works can’t really be attached to a firm timeline because the number of people falling ill has more to do with how much virus is circulating around at any given time. Right now, there’s a lot. With the U.S. currently at record rates and hospitalizations, and accelerating.

Which is why guidelines from a lot of people including the CDC and President-Elect Joe Biden to wear a mask for a couple of more months seems to me at least, to be so important. You don’t want to trip and fall, or trip up a family member, just as the finish line may be coming into sight.

Both the Moderna and Pfizer vaccines are based on mRNA, and while mRNA vaccines and treatment have been in development for a while, none has been approved or marketed before.

Most of the coverage we’ve been seeing of these vaccines just kind of leaves it at that.

We wanted a bit of a deeper explanation, especially since it might be something someone’s going to inject inside us soon, and we remembered we’d written a piece about mRNA vaccines back in May. So the rest of what we’re going to present today is us cribbing from ourselves back then.

And we will state up front that this too is an over-simplification, but hopefully will contribute to a marginally better understanding of what this type of vaccine is all about.


Just what is an mRNA vaccine anyway?

Moderna’s and Pfizer’s vaccines are built on something that’s never been done before with vaccines. So there’s no real data on how safe it is for humans as time goes by. So even though this type of vaccine has never been used in humans before, there won’t be years of trials behind it to figure out whether it’s totally safe, because there can’t be. By the time most people are getting injected with it, if things go really well, it’ll probably have been in use for about 6 months, so that’s about the data we’ll have. Now, already there are some long-running clinical trials for mRNA vaccines and treatments aimed at certain types of cancer and also respiratory diseases, so there might be some safety data that can be culled from those studies, although none of those is actually officially in use yet.

Will most people take an RNA vaccine for COVID-19 anyway if it’s shown in trials to protect effectively against the virus, and lets them get fully back to their lives?

In May, when I originally published the non-italicized part of this, my answer was a resounding. “Yes”. Now, I definitely would. But we’re not still quite so sure about others…I mean, if they won’t even wear a mask?!

Is the vaccine likely not to have horrible long term effects on people? For reasons we’ll explain in a sec, probably.

Right now, most every vaccine humans get is made up of a dead or weakened form of a virus or disease you’re being vaccinated against, giving your body the ability to manufacture antibodies against the disease without you getting very sick. RNA-based vaccines, like the one we’re talking about, don’t work that way at all.

With RNA, instead of giving you enough of the “bad stuff” to stimulate you to produce antibodies without making you sick, you get injected with a bit of genetic code that’ll get you to make something resembling the “bad stuff” yourself, and then make the stuff that’ll snuff that “bad stuff” out.

Here’s a little illustration of the way it works from a very informative Harvard University science blog:

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So with an RNA vaccine, you actually get injected with genetic material, which your cells then use to create an antigen, which your immune system then creates antibodies against. Instead of a normal vaccine where you get injected directly with the antigen.

So is that more safe than a conventional vaccine? Less safe? The same?

The Harvard blog likens an RNA vaccine to providing a chef (your body) with a recipe (the RNA code). The “ingredients” are in your body already. The vaccine just tells your body how to make it. And then you, the “chef” takes over and whips it up. Following that analogy along, the Harvard piece asserts that means it’s very likely safe because:

“Injection of RNA presents no risk of disrupting the cell’s natural DNA sequence. To continue our kitchen analogy, disruption from DNA is like inserting a foreign ingredient in an existing recipe, which can change the resulting dish. Injecting RNA, on the other hand, is like temporarily adding a new recipe in the cook book while keeping old ones untouched, and therefore will not result in surprising changes to existing recipes.”

Convincing?

We can see how it’s easy to feel this is how many sci-fi/end-of-the-world/zombie movies start.

At the same time, we’d be willing to take the shot if we see a lot of evidence it really works and seems to be safe, and someone we respect tells us the same: it’s very, very likely very effective and very safe. So at the very least it’ll mean education about the product and endorsements from voices Americans (and people around the world) trust, may become almost as important as its effectiveness.