Home About My Books Résumé Chronological

Covid Vaccines

Created/Modified: 2020-12-03/2020-12-03

A friend asked my thoughts on the safety of the new vaccines, given how quickly they have been created, and I figured it was worth talking about here as well.

I don't have any reservations about these vaccines.

There are two reasons they have come online so quickly: vast amounts of money, and better technology.

The money is mostly in the scale of trials, which have been a factor of ten (or more) larger than the largest Phase 3 trials seen in the past. Tens of thousands rather than thousands, so the statistical power is enormous, especially given the prevalence of the disease. Some places we're seeing 0.1% of the population getting infected every day, which is a huge number, so the number of cases showing up in the control population has grown rapidly.

The "statistical power" of a trial or experiment is fundamentally determined by simply counting the number of events in a given population. A trial runs by recruiting people and assigning them at random to one of two groups. The "control group" gets injected with saline solution, a harmless procedure that does nothing except ensure that no one knows who is in which group. The "treatment group" gets injected with the vaccine. The larger the groups, and the bigger the number of events in the control group compared to the treatment group, the higher the power of the trial.

The trials that have produced results so far are very highly powered and were put together faster than I had thought possible, which is both a result of money and (probably) ease of recruiting. If I'd had a chance to take part, I would have. Wouldn't you?

The technology aspect is important on two fronts: one is that mRNA vaccines (Moderna and Pfizer) are constructable in an extremely short time, because we know how to build RNA sequences. It's standard bench-top technology. mRNA is what the body uses to translate our genes into proteins, and an mRNA vaccine consists of two parts: the mRNA payload itself, and the encapsulation, which is a lipid (fat) nano-particle that is capable of penetrating the cell membrane. The thing about mRNA is is has a very limited lifetime in the body. Otherwise our cells would clog up with all the mRNA we are continually making naturally as part of the process of living.

So what happens with an mRNA vaccine is you get an intramuscular injection, the cells in the vicinity take up the lipid nano-particles and the mRNA gets pulled in by the cellular machinery which makes the coronavirus spike protein, and your body's immune system sees it, builds anti-bodies against it, and programs T-cells to react to it.

Then when you encounter the natural virus, all those defences are ready and waiting. The virus never stands a chance. By that time the mRNA is long gone, but your immune system is like an elephant: it remembers.

The same is true for DNA-based vaccines (which the AZ/Oxford vaccine is): the technology to build a DNA sequence and splice it into a carrier adeno-virus is well-developed. Despite some protocol issues, the vaccine is probably effective and safe (although let's wait on review to find out!) The fact that protocol issues were discovered should be taken as reassuring: it means that the oversight mechanisms in place are working!

And if you think "sometimes humans make mistakes" is a new discovery that is some kind of bombshell reveal, I've got some bad news for you...

In any case, both these techniques are essentially constructive: we build a gene sequence and attach it to a carrier so it can get into the cell and manufacture the spike protein which triggers the body's natural immune response.

Remember, the way cells make things goes like this:

DNA => mRNA => proteins

The AZ/Oxford vaccine cuts in at the DNA stage by using a harmless virus with a bit of extra DNA for the spike protein. The mRNA vaccines insert their own messages in the middle of the chain rather than at the source. In both cases they make only what they want, with very little extra baggage (in the case of mRNA vaccines the extra baggage--the lipid nanoparticles--aren't even biologically active.)

Both of these constructive approaches are quite different from the traditional technique of creating an attenuated virus vaccine, which is comparatively tricky and dangerous, and therefore takes much longer because the risks are higher.

In those cases you have to figure out a specific intervention to modify the real virus so it will generate the protein you want the body to react to, but not do anything dangerous.

That's much harder than taking only the gene for that one protein and either injecting it directly as mRNA or splicing it into an adenovirus carrier. In those cases you are just adding the gene for the protein to a known-safe vector (a lipid nano-particle for mRNA vaccines, a benign adenovirus for DNA-based vaccines). In the denatured-virus case you are trying to remove certain capacities from the whole (otherwise-deadly) virus.

Since you know the specific protein you want is safe without the rest of the virus, the first case is inherently much safer.

Analogy: you want the soft feeling of polar-bear fur to rub up against (because really, who doesn't?)

You can either buy a bear-skin rug (bringing only the part of the bear you want into your home) or you can try to breed a non-violent polar-bear (difficult and dangerous!)

That's the difference between modern and traditional vaccine development technologies.

The Phase 3 trials we've heard about so far have shown not only the vaccines are effective, but they are safe: the rate of adverse events in the people who got the vaccine are no higher than the rate in the people who got the placebo. This is not surprising, but it's very good to know.

Were there zero adverse events in the treatment group? Don't. Be. Stupid. Take any population of 10000-plus people over a few months and some bad things are going to happen to some of them. The only thing that matters is: was the rate in people who got the vaccine higher than the rate in the people who didn't? The data--we are told--show the vaccine is safe.

The one thing that remains is for these results to be fully published. Review by regulators is great, but I'd really like to see the results pass peer review and get out into the world.

We can expect that to happen soon, but even if it takes a little longer (because preparing data for publication is insanely hard and the people doing it have some higher-priorities right now in making sure the results are actually correct and making sure regulatory agencies have all the information they need) I will be lining up to get jabbed when a vaccine gets approved by Health Canada.

Contact Home
Copyright (C) 2018-2019 TJ Radcliffe