COVID-19: So Many Vaccines…So Little Time

A friend of mine asked me how the “other” vaccines work (the ones not from Pfizer/Moderna) and I’m glad he did because, to be quite honest, it’s been a while since I wrote one of these. Also, I was rereading my mRNA vaccine post and I felt it could use some improvement because I don’t think it did a good job of explaining mRNA vaccines exactly the right way.

Allow me to try and correct that error and at the same time, explain some of the other versions of the vaccine that exist out there. Big shout out to Dr. Paul Volker, also here at DMU, who helped me prepare this.


How do vaccines work?

Quick vaccine refresher: inactivated vaccines are the dead, inactivated protein coats of viruses. They are what the virus is “wearing.” It’s like holding a uniform of an enemy soldier up in front of your body’s army and saying, “See this? Go kill everybody wearing this.” Then your immune system does it in a cool and complicated way because your immune system is dope.

Live attenuated vaccines are like taking an enemy soldier (the virus), beating the heck out of him, and putting that in front of your body’s army and saying, “See this guy? You go find everybody that looks like him and really go at them.” And then your immune system does it in cool, complicated way because your immune system is dope.

Now the cool, complicated way your immune system does this (among other things) is by looking for certain things called antigens. Antigens are sort of like markers on a virus that your body can recognize as being bad/a part of the virus. When your body’s immune system recognizes a virus antigen, your body can make antibodies in response. You have cells called B-lymphocytes that crank out these antibodies, which attach to the viral antigens and then your other cells go and take out the tagged offender. It’s like an exploding ink pack in a stolen bag of money from a bank; when the ink explodes, we all know who stole the money and the police know who to chase…when the antibodies attach to the antigens, your body’s immune system, specifically cells called macrophages and the very aptly named “Natural Killer Cells” (among others) go and chase down the virus.

Refreshed?  Good.

Antigens and spike proteins

Now, the antigen in question is at the heart of everything we’re talking about here. The viral antigen we care about is something called a spike protein. Spike proteins are the proteins on the surface of the virus that allows the virus to penetrate and insert its genetic material into your cells. The spike protein is what we’re targeting here. Now at this point I need to take a quick detour and it is relevant to how the vaccines work. There are several things we have to understand about viruses:

  1. Thing #1: Viruses are not alive. They don’t check the boxes because they can’t reproduce on their own.
  2. Thing #2: If we wanted to pretend viruses have personality, there’s only one thing viruses want: to make more of themselves. That’s the entire goal of a virus. Remember Agent Smith in the second installment of the Matrix, making copies of himself? That’s what viruses want to do.
  3. Thing #3: Viruses do this by hijacking your stuff!

Remember that spike protein? See, the purpose of that is for the virus to inject its genetic material into your cells. The reason it does that is because it’s trying to hijack YOUR cellular machinery to make more of itself. That’s how viruses work…they hijack YOUR STUFF to make THEIR STUFF. We’ll talk about how we take advantage of this in just a bit.


what’s the difference between the coronavirus vaccines?

Alright, so we know what viruses want to do and we know how they do it. We also know that the spike protein the viruses use is a bit of an Achilles Heel. That’s the thing we can use to identify them. 

Now one of the problems with coronaviruses in general is that they have something called an envelope around them. The envelope allows the coronavirus family to evade your natural defenses and that’s why our original two vaccines—live attenuated and inactivated up there—don’t work quite as well. Coronavirus envelopes allow them to slip around the way we’d normally do this. 

But that spike protein…the coronavirus can’t hide that, so that spike protein is what we focus on. And that has led to three different approaches in vaccine development: mRNA vaccine, protein-based subunit, and non-replicated viral vector. Don’t worry, I’ll explain what each of these are. Let’s start with the easiest one: protein-based subunit.

Protein-based subunit vaccine

A protein-based subunit vaccine is being developed by NovavaxAB, Sanofi, and GlaxoSmithKline. This is probably the simplest of the three. Essentially, they purified the spike proteins, put them in a vaccine, and injected them. Your body sees the proteins, recognizes them as foreign, knows to look for them again, and when a coronavirus with the same spike protein shows up, your body tags it and bags it. That’s it. Easy peasy, lemon squeezy.

mRNA vaccine

The second one is an mRNA vaccine. Now, I initially wrote about mRNA vaccines and this is what I wish I would have done a better of explaining: The mRNA vaccine is a set of instructions on how to make the spike protein. It’s spike protein blueprints. You have all sorts of bits of mRNAs floating around your body—like, trillions. Each mRNA is a set of instructions for making specific proteins (and have a look at the old mRNA vaccine for a discussion on proteins…that actually was pretty solid).

Anyway, the companies Pfizer and Moderna figured out how to artificially make mRNA sections that code for the spike protein. Your body finds the mRNA floating around in your shoulder muscle after you got the shot and says, “Huh…wonder what this does…I think I’ll run it through a ribosome and see what protein comes out.” If you forgot 7th grade biology, a ribosome is the protein maker in all your cells.

So when this happens, the protein that comes out is a spike protein. Your body then says, “Huh…I don’t recognize this spike protein and I don’t think I like it…B-cells! Whip up some antibodies and tag the next thing that shows up here that has one of these spike proteins. Natural Killer Cells…do your thing. Really go after anything tagged, yeah?”

It’s this last part I did a lousy job of explaining in the mRNA vaccine post; I got a little too excited about how cool this actually is and simplified it too much.

Anyways, that’s how the mRNA vaccine works.

Non-replicating viral vector vaccine

Now the non-replicating viral vector vaccine, that one’s really crazy. AstraZeneca, Janssen, and Johnson & Johnson are developing these. Here’s how they work:

You remember how vaccines hijack your stuff to make more of themselves, right? Well, we actually take advantage of that. The good folks at AstraZeneca, Janssen, and Johnson & Johnson figured out how to take a genetically altered adenovirus, and that’s the vaccine. You read that right—a virus IS the vaccine. See, when the virus infects you, instead of making more of itself, it hijacks your cellular machinery…TO MAKE SPIKE PROTEINS. We tricked a virus into infecting your cells with the instructions on how to make spike proteins! What a sucker of a virus! We did this with something called a plasmid and incidentally, this is the same way we make insulin now.

I know it seems disconcerting to use a virus to do this work. You might be wondering, “What in the heck’s an adenovirus?” Consider, though, that you get infected with viruses all the time. If you’ve ever had a cold, or diarrhea, or pinkeye, chances are pretty good it was an adenovirus that did it. You’ve already had one, and this one doesn’t even want to hijack your stuff to make more virus, it just wants to hijack your stuff to make spike proteins and it’s this aspect that makes the adenovirus infecting you fairly benign (that’s why it’s called a non-replicated viral vector—the virus doesn’t make more of itself; hence, non-replicating).


What type of coronavirus vaccine should I get?

So, it all centers around spike proteins. That’s the game here. And there’s three ways to do it. Here’s the recap:

So, which is the best? To be honest, we’re not exactly sure. Currently it would appear that the mRNA vaccines seem to be working the best, but more data is needed. As to why the mRNA vaccine seems to have the best efficacy, well…I’m afraid that question is a bit beyond my pay grade and scope of knowledge. Even if I did know (and I don’t), I doubt that can be easily explained.


What about the coronavirus mutations I’ve heard about?

Now your next question might very well be…okay, what about the mutations I keep hearing about? A very valid question, to be sure. The beauty of targeting a spike protein is that those spike proteins are pretty specific to coronaviruses, irrespective of mutations. But it’s true enough, another round of vaccines may be needed.

As to why coronaviruses mutate…well…that was another post for another day, but if you want, you can read about it here.


The expert family medicine providers at the Des Moines University Clinic are here to help you and your loved ones stay healthy year-round. If you think you or your family have been infected with COVID-19 and live in Polk County, call 2-1-1. If you have an upcoming appointment at the DMU Clinic please call in advance. More information is available on DMU’s coronavirus response website.

Disclaimer: This content is created for informational purposes only. It is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of a qualified health care provider with any questions you may have regarding a medical condition.

Jonathan Crosbie, D.O.

Dr. Crosbie is an assistant professor in the Departments of Osteopathic Medicine and Family and Internal Medicine at Des Moines University. In addition to his academic responsibilities and providing excellent patient care in the Family Medicine Clinic he is an avid activist for preventative medicine and living a healthy lifestyle. In his spare time he enjoys motorcycling, woodworking, movies and sports, and spending time with his family.

Scroll to Top