- This is how coronavirus invades your body, sinking its crown-like spikes into your cells, using molecular deception to pick their locks, and hijacking your body.

But there is one way to prevent this, by using one of the viruses weapons on itself.

Hey, smart people, Joe here.

Right now, there's about 7 billion people, all waiting for the same thing, a vaccine that will protect us from the virus causing COVID-19.

And if you're like me, you want to know what's in it.

What makes it work?

Making a vaccine and getting it out to the public is a long process with a lot of steps, so we can make sure the vaccine is safe and effective.

That's pretty typical for that to take 10 years or more.

In an emergency like this pandemic, well, we can't skip any of those steps, but we can speed this up by doing some of them at the same time.

But none of that can happen until you figure out the first step.

What do you put in your vaccine that will make it protect people?

And that's what we're going to talk about today.

We're going to visit a lab and meet some scientists who study the coronavirus.

We're also going to meet a really big awesome science machine and learn how they used it to design this, the key ingredient inside the very first COVID-19 vaccines.

Now, here's my goal with this video: to show you what exactly is in the new COVID vaccines that makes them work and how they got made faster than any vaccine in history.

My hope is that you'll be better informed when you get your shot and you'll have a new appreciation for why science like this is so important.

This is how to make a COVID-19 vaccine.

(upbeat music) It turns out that some of the most important research for making the COVID-19 vaccine is happening right down the road from me at the University of Texas, which is pretty cool, because I did my PhD right here.

And in here is the lab of Dr. Jason McLellan.

He studies how pathogens like coronavirus caused disease.

- There are four human coronaviruses that occur seasonally and generally cause the common cold.

And then there've been three coronaviruses that have caused pandemics.

And that's the first SARS coronavirus back in 2002, the MERS coronavirus in 2012, and now SARS-CoV-2, which emerged earlier this year.

At the end of December 2019, it was on the news that there was these pneumonia clusters in China.

In the scientific community, we thought maybe a new flu virus or possibly a coronavirus.

I was actually snowboarding with my family and my collaborator, Barney Graham, at the vaccine research center at the NIH, called.

And he said, he's been in contact with US CDC, Chinese CDC.

It looks like it's a betacoronavirus similar to SARS and they wanted to move rapidly, try and make a vaccine.

And I said, we're definitely in.

- So you're just like scrolling through your phone in this ski lodge.

You're like, "We got to get to work!"

So while the rest of us were focused on royal family drama and just hearing the first mentions of coronavirus for the very first time, scientists like Jason knew this was serious and they were already getting to work.

As soon as researchers in China decoded the viruses genome and published it online, Jason's lab could start designing a vaccine.

- I texted Daniel Wrapp, my graduate student, and let them know be on high alert, because as soon as we get the sequence, we're going to move as quickly as we can.

- Jason was on that winter vacation and texted me that it was a coronavirus.

And eventually in early January, the sequence was released online publicly.

And then things started moving pretty quickly.

- Let's step back for a minute.

What does a vaccine do?

Well, it trains your immune system to know what a germ, like a virus, looks like, so that it can recognize the germ, fight it off, and keep you safe without you getting sick.

This is the virus that causes COVID-19.

The outer shell is made of a few different kinds of proteins, but these proteins sticking off the side are the most important part, the spike.

These spikes are what give this family of viruses, their name, the coronaviruses because they look kind of like a crown.

The coronavirus uses that spike to sneak into our cells.

The three-dimensional shape of that spike is super important because that exact shape is what lets the virus latch onto receptors on the outside of our cells, almost like picking a lock.

And then, it sneaks inside.

Those shapes sticking out on the outside of a virus are also what your immune system is feeling for to figure out if this is a foreign invader, if it should attack or not.

The problem is the first time your body sees a virus, your immune system responds so slowly that the virus has time to make gazillions of copies of itself.

And you can still get very, very sick.

That's what's great about a vaccine.

It trains your immune system what to look for, so when the real virus shows up, your body can respond super fast and destroy the virus before it has a chance to hijack your cells.

So what's actually in a vaccine?

Well, sometimes the vaccine has a weakened or dead virus.

That's how polio and measles and mumps and some other vaccines work.

But these days, a vaccine usually just contains a little piece of the virus.

The newest COVID-19 vaccines, they're just the spike.

But for that spike to work as a vaccine to train your immune system to recognize the actual virus, it has to have the same three-dimensional shape as the spike on the whole complete virus.

But making a spike all by itself not attached to the rest of the virus, that turns out to be really hard, because the spike is actually pretty floppy just floating around on its own.

It doesn't look much like the spike on the actual virus.

And this is the key thing Jason's lab figured out how to make.

For years, they'd studied SARS and MERS viruses, which are really closely related to the virus that causes COVID.

So they already knew what tiny tweaks to make to freeze the coronavirus spikes into the perfect shape.

- So we got to work designing our stabilizing mutations into the new spike sequence.

There was just two amino acids that we knew would, if we mutated them, it would stabilize the spike protein and make it a lot easier to work with in the laboratory.

- A protein like the coronavirus spike is a long folded string of individual units called amino acids.

And these strings of amino acids are built using code written in RNA and stored in DNA.

By changing or mutating the letters of DNA code, we can change the amino acids in our protein string.

So, that's cool.

So you're like building scaffolding into the protein to be like freeze in this, in this shape.

- Yeah, that's a good way to put it.

- How do you from there to making the actual spike protein?

- Ah, I can show you.

- [Joe] Scientists are able to grow special immortal human cells outside the body, which they use as factories.

They put a modified gene or something like their spike protein into those cells.

- [Daniel] And then they'll start spitting out this protein.

- [Joe] So they're just pumping it out into the liquid.

- [Daniel] Yeah, that's right.

- They take that liquid, run it through special purification machines, and are able to isolate a pure sample of their spike protein.

But how do they know for sure that this special spike protein looks like the real thing, 3D shape and all?

Well, they take pictures of it using a big, awesome science machine.

This is a cryo electron microscope.

This machine took a 3D picture of the coronavirus spike and helped design the very first COVID-19 vaccine.

Check out the big science machine.

- [Jason] Looks like a giant microwave.

I mean the room is like a million dollars, and then, the microscopes another million.

- So you're saying don't touch this screen or anything.

- So you can see like the floor is separate from the instrument.

So it's on its own, vibrations are bad.

These are wall panels that contain water running behind them to keep the temperature constant in the room.

And then it also has to be electromagnetically shielded too.

- [Joe] That is nuts.

What is this beefy cable over here?

- So that's the 200,000 volts coming from that.

- [Joe] Okay, yeah, so don't lick that one.

Oh, this is sciency.

Look at all that science happening in there.

- [Jason] Kind of a marvel of physics and engineering.

- [Male Speaker] Can you play Doom on this thing?

- Some of our computers, you'd be able to play at max settings.

- So maybe this sounds like a super stupid question, but why can't you just use a regular light microscope to take a picture of a protein?

Well, the wavelength of visible light is on the order of hundreds of nanometers.

And that means the smallest things you can see with visible light are also on the scale of hundreds of nanometers.

But what we want to see, the atoms in a protein molecule, they're angstroms apart, tenths of a nanometer.

So we can't use visible light.

We have to use a special electron microscope.

So super high energy electrons make very tiny wave lengths, which lets you see very, very small resolution things.

- That's right.

- Okay, I want a camera like that.

That's better than 4K.

We can go angstrom K. So to take a 3D picture of a protein with a cryo electron microscope, first, you put a drop of protein onto a special metal grid.

Then, you freeze it in place with liquid ethane.

When we shoot a beam of electrons at it, these proteins will be in all kinds of random orientations.

Each orientation leaves a particular shadow.

Powerful computers look at all of those 2D images and then combine them into a final 3D shape.

It's kind of like using a bunch of 2D photos to make a 3D model.

And when Jason and Daniel and their team looked at the spike that they made with their tiny little tweaks and mutations, their spike has the same 3D shape as the spike on the whole virus.

Pretty cool.

Now we can put that spike into people and see if it trains their immune system and protects them from the real virus.

And it works.

This protects people from COVID-19.

The research you just saw from those scientists is literally what's being used in the very first COVID-19 vaccines.

And some of those vaccines work in a really cool way.

Instead of having to make the actual spike protein in these big factories with huge tanks of cells, like the ones that we saw, some of these new vaccines, the genetic instructions for making the spike is all that's in the shot on a molecule called MRNA.

Your body uses those instructions to make the spike.

You are the factory.

That's awesome.

I mean, this is a really incredible piece of science.

A year ago, no one had ever seen this virus before.

And thanks to these scientists and thousands of others around the world, now we have vaccines that work.

I mean, it's going to take months, maybe years to get these vaccines and the dozens of other still being worked on to the billions of people that need them.

And that's a huge challenge on its own, but this is a really hopeful story.

No vaccine in history has ever been invented this fast, and we were able to do it safely.

We were able to do this so quickly because scientists like Jason and his lab and others, they were ready, because they were studying basic scientific questions about other coronaviruses, SARS and MERS.

They've spent years trying to figure out their secrets, so that when this one showed up, they were already 10 steps ahead.

And to me, that's why work like this, supporting basic research, is so important and why we need it.

Stay curious and get your vaccine as soon as you can.

I am really ready for this to be over.