COVID-19 Vaccine Questions

In my medical clinic, several people have asked me about the COVID-19 vaccine. I appreciate their trust in helping them make health decisions.

One concern that has been raised is the speed at which the vaccine was developed. Does this mean corners have been cut? Is it enough time to know that the vaccine is safe? These are good questions.

I think we can have high confidence that it is safe. Here are a few points to consider when you think about the speed at which the vaccines were developed.

We didn’t start from scratch

With typical vaccine development, you’d probably need an average of 4 years to go from beginning to human testing. COVID-19 was done within about 9 months.

It’s important to realize that the 9 months wasn’t the start date. We owe a lot to people who have toiled for years or decades to have this technology ready when we needed it.

SARS–A Dry Run?

Some of us may remember SARS (Severe Acute Respiratory Syndrome) virus. This outbreak of a new coronavirus started in February 2003.

It was a lot like COVID-19 turned out to be. In fact, the official name for the COVID virus is SARS-CoV-2 (SARS Coronavirus #2). It shares about 80% of its genetic code with COVID-19.

Happily, a great deal of work had been done on a SARS vaccine (though fortunately SARS was less contagious than COVID, and so was controlled with local lock-downs and public health measures like contact tracing).

A lot of the nations that got hit hard by SARS did much better this time around–they had put public health measures in place to respond if something similar happened. In retrospect, it’s probably a good thing we had SARS to prepare us for COVID (even though many nations, including the US and Canada, did not learn the lessons they should have).

mRNA vaccine platform is not new

You can think of the mRNA vaccine approach as a “gun”–and the gun has been worked on for almost two decades. This is the first human vaccine built with it, but there’s been a lot of work on other viruses, and a lot of animal testing.

Part of the goal with the mRNA approach was to build a “gun” that you could use every time. You would then only have to craft “a bullet” (the mRNA of the specific virus you were after) in the event of an outbreak. So, as soon as the Chinese scientists published the RNA sequence of COVID-19, within hours work on the mRNA could begin.

This means that a great deal of safety work has already been done on the “gun”–it’s had far more than 9 months of use, refinement, and testing.

mRNA vaccines are faster to make

One of the appealing things about mRNA vaccines is that you can make them faster. One goal was to have the gun ready, and then store the genetic code of various possible infections. If there was an outbreak, you could just turn it on and go.

Vaccines up until now have used biologic synthesis. That means that making whatever it was you put in the vaccine involved growing things in a lab. You needed to culture a weakened organism (like the Salk polio vaccine).

Or, like the flu vaccine, you’d have to grow the proteins you were going to use in tissue culture. This takes time, and then you have to extract and purify the protein for use.

This is not quick (which explains why with the flu vaccine, we have traditionally had to simply “guess” what strain is likely to circulate, and then start making the vaccine ahead of time. Sometimes they guess right, and sometimes not so well–which explains how the flu vaccine varies in its effectiveness.)

But, mRNA vaccines aren’t like this–aside from the pre-built gun, you just have to make a string of mRNA. That can be done with chemical synthesisno living organisms, no growing in cell culture, just industrial chemistry. Put stuff in a vat or test tube, and let ‘er rip. And that is something that industry is very good at, and fairly quick.

In short, comparing mRNA vaccine turn-around times to other vaccines just isn’t fair–its two completely different processes and time frames. Which is a good thing!

Targeting the spike protein

One trick with viruses–especially RNA viruses–is that they mutate. Everyone knows how the flu changes every year. So for a vaccine to work, you need a “steady target” that doesn’t change from year to year. We’re lucky with COVID in that it has a “spike protein”–this is the protein that fits like a key into a lock. In this case, the lock is the ACE2 receptor, which is how the virus gets into your cells.

There can be mutations in that protein (and there have been–the three new strains from US, UK, and Brazil that are more infectious all have mutations in their spike protein). But–and this is very important–the shape of the protein can’t change too much, because it still has to fit like a key in the lock.

You might be able to file off a key a bit to get a better fit in the lock. That’s like the new mutations. But you can’t shave of large bits of the key and still work the lock.

The vaccine targets the spike protein because it is a relatively stable shape. It can mutate, but large mutations in shape will almost certainly die out quickly because they can’t get into cells to reproduce. In evolutionary terms, they are selected against. So that single target doesn’t change enough to make the vaccine not work.

A single protein is less likely to cause a reaction

Targeting the spike protein has other advantages. It is a single target for your immune system. In the old days, the killed pertussis vaccine used to have at least 3,000 proteins on it (see my article here, especially the end bit, for more on this). That’s still a drop in the bucket compared to what your immune system handles in a day, but it gives more chance for a “cross reaction” to happen between a protein on the bacteria, and a protein on a human cell.

If you look at all the vaccines given to children in the US as of 2013, there are only 315 protein exposures (“epitopes,” in technical language). That’s incredibly low.

But the mRNA vaccine for COVID is even better. It’s one. So there’s an even lower risk of a reaction to it.

How about how long we’ve watched for problems?

The clinical trials for COVID-19 were not terribly long–less than a year. How can we know that there won’t be longer-term problems?

One can never be certain about such things. But, remember, the “gun” isn’t new. And that gun with a variety of bullets has been used in a lot of animal studies. And experience has shown that any reactions or problems are likely to be seen in the first few months.

We could wait years to be certain–but that means COVID kills more people and causes way more financial damage to the economy. That’s a very high price to pay for something we have no evidence happens, and considerable evidence that it doesn’t.

What about drug company bias?

Maybe the drug companies are going to be over-optimistic?

I don’t worry about this–the Pfizer study, for example, had over 40,000 people. That’s huge. And the study was blinded–neither the patients nor Pfizer knew who was getting the vaccine and who got the placebo.

Pfizer never had access to that data. There was an independent panel who decided when to release the data. So Pfizer couldn’t cook it even if they wanted to.

That independent committee is, if anything, going to be biased against releasing something prematurely. They don’t want the professional or personal costs of being “the guys who let the bad vaccine get through.” So they will tend, if only out of self-interest, to be conservative.

That gives me considerable reassurance, because even the worse aspects of human nature (e.g., seeing what you want to see, lying) will act as a check and balance on releasing a bad vaccine. (It’s sort of like the US Constitution in that sense–balancing potential bad behaviour by another group with separate interests.)

Really, it’s the best way to do this kind of science.

And besides, there’s no way Pfizer will make enough from the vaccine for it to run the risk of releasing something that doesn’t work or causes bad problems. They don’t want their name to be mud.

Two vaccines

Thus far, we have two mRNA vaccines–Moderna and Pfizer. They were developed separately.

And yet both got results within about 1% of each other: 94-95% protection.

That’s a nice bit of reassurance–there wasn’t something weird or fluky about the data. Nobody is likely to have cooked it. You have two different groups, using a similar but not identical approach. And they score within 1% of each other.

That suggests to me that this is a real effect–you can trust it when you have independent confirmation like that.

Investment helps

Contrary to popular belief, vaccines are not a huge money-maker for drug companies. Relatively speaking, fairly little money up until now was invested in this kind of tech. It’s been more basic research.

A pandemic, however, is a good way to convince private companies, individuals, and governments to open up their wallets. More money invested can gain you speed, which is what happened here. (There’s an old engineering joke: it can be fast, cheap, or good–pick two. In this case, we’ve picked good and fast, at the price of cheap.)

Conclusion

As should be obvious, I’m quite confident in the vaccine. I’ve been fortunate to get my first dose (Moderna, because that was all they had) already. I had a sore arm about 24 hours later, but otherwise, nothing.

So, I have put my money where my mouth is.

Nothing in medicine is ever 100% risk free. But that’s true of doing nothing as well.

Doing nothing has risks. It has upsides, and downsides. I think the benefits to me and society of getting control of the pandemic with a well-tested system (in animals and now humans) are far bigger than the small risk I run of a problem. If we do nothing, we’ll have more death and more financial catastrophe for many people. I don’t want to contribute to that, even though I myself am at very low risk of death were I to catch COVID-19.

In medicine, we call that “a no-brainer.”

Personal postscript

Most who read this know that I’m a religious person as well as someone who works in medicine. I’m very grateful for the rapid progress that was made on this front. Many things were in place that allowed us to make great progress faster than we maybe had a right to. As a society, we have been foolish in ignoring warnings about risks for pandemics, and our elected representatives and the attendant bureaucracies have not covered themselves in glory.

So, I see the vaccine as very much a “godsend.” It is, I am convinced, an answer to many prayers. I hope we’re grateful, and I hope we’ll use it properly and well. It would be a shame if the speed at which we got there ironically made us less grateful, more suspicious, and less willing to use the wonderful tool that has dropped in our laps. (Though the work of many for decades was needed to have it “so quickly”! God is much better at preparing ahead of time than we are.)

And hopefully we’ll be more ready next time–because you can bet there will be a next time. I suspect this isn’t the last time we’ll be profoundly grateful for this type of vaccine tech that can be deployed so rapidly. That’s the part that excites me the most, even more than an end to COVID.