Public Health World Update

COVID-19 Science ! How is Vaccine developed?

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.  And it’s pretty typical for that to take ten 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 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 it’s what we’re going to talk about today. We’re gonna visit a lab and meet some scientists who study the coronavirus.   We’re also gonna 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. 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. 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 the coronavirus cause 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. So at the end of December, 2019, it was on the news that there’s these pneumonia clusters in   China. Uh, 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. Uh, it looks like it's a betacoronavirus similar to SARS coronavirus, and   they want it 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, and you're like we gotta 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 virus’ 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 race on this thing and move as quickly as we can. Jason was on that winter vacation and texted me that it was a CoronavirusAnd eventually   in early January, the sequence was released online publicly. That's when the clock started ticking because we   knew a bunch of people were going to be working on this. Uh, and then things started moving pretty quickly… Let’s step back for a minute. What does a vaccine do?   It trains your immune system to know what a germ, like a virus,   looks like. So 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, butthese 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 kinda like a crown. The coronavirus uses that spike to sneak into our cells. The 3-dimensional shape of   that spike is super important, because that exact shape is what lets the virus latch on   to 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? Sometimes, a 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 3-dimensional shape as the spike on the whole, complete virus. But making the spike all by itself,   not attached to the rest of the virus, 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 coronavirus spikes   in the perfect shape. Um, so we got to work designing our stabilizing mutations into the   new spike sequence. There was just two amino acids that we knew would, uh, if we mutated them that   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 “mutuating” the letters of DNA code, we can change the amino acids in   our protein string. So that's cool. You're like building scaffolding into the protein, to be like   “freeze in this shape.”   Yeah, that's a good way to put it.  How do you get from there to making the actual spike protein? I can show you…  Scientists are able to grow special immortal human cells outside the body which they use as   factories. They put a modified gene for something like their spike protein, into those cells… …and then they'll start spitting out this protein So they're just pumping it out into the liquid, right? 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, 3-D shape and all? They take pictures of it… …using a big Awesome Science Machine. (VO) This is a cryo-electron microscope.  This machine took a 3D picture of the coronavirus spike,   and helped design the first COVID-19 vaccines Check out the big science machine! It looks like a giant microwave Am I ok to walk up here? Yeah, it’s ok. I mean the room is a million dollars, and the microscope is another million.  So you’re saying don’t touch this screen right here. You can see the floor is separate from the instrument, it’s on its   own, free-floating. So vibrations are bad.These are wall panels that contain water   running behind them to keep the temperature constant in the room. Oh wow, that’s… Then it also has to be electromagnetically shielded too.  That is nuts. Look at this beefy cable over here. That’s the high-tension, that’s the 200,000 volts comin in over here Oh ok, so don’t lick that one! Oh this is… Sciencey! Look at all that science happening in there.  It’s kind of a marvel of physics and engineering. Joe N (OS): Can you play Doom on this thing?  Um, some of our computers you can play Far Cry 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 wavelengths, which lets you see very, very small resolution things. 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,those   proteins will be in all kinds of random orientations, some like this, some like that. Each orientation leaves a particular “shadow”. Powerful computers look at all those 2D images, and combine them into a final 3D shape. It’s kind of like using a bunch of 2D photos of someone’s head to make a 3D model. And when Jason and Daniel and their team looked at the spike they made, with their   tiny little tweaks and mutations, their spike has the same 3D shape as the spike on the whole virus. 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 big factories, with huge tanks of cells like the ones 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. 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. It’s gonna take months, maybe years to get these vaccines, and the dozens of others still being   worked on, to the billions of people that need them, and that is 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.  And 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 when this one showed up, they were already ten steps ahead. And to me,   that’s why work like this—supporting basic research—is so important, and why we need it. Stay curious…

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