Speaker 1: School of Humans. In nineteen sixty six, an outbreak of
Speaker 1: respiratories and sicial virus spread through Washington DC. RSV is
Speaker 1: a highly contagious virus that usually pops up in the
Speaker 1: colder months. It can block the airways of infants and
Speaker 1: cause pneumonia in older adults. Tens of millions of people
Speaker 1: get sick from it every year, and thousands die. To
Speaker 1: stop those deaths, a team at the National Institutes of
Speaker 1: Health created some RSV vaccines and tested them in babies,
Speaker 1: mostly babies from poor black families. The trial went badly,
Speaker 1: really badly. Dozens of infants got a new RSV vaccine,
Speaker 1: and not only did the vaccine not protect them from
Speaker 1: the virus, it actually seemed to expose them to graver sickness.
Speaker 1: So the vaccinated babies who caught RSV fared worse than
Speaker 1: those who got no vaccine at all. Eighteen of those
Speaker 1: kids ended up in the hospital and two of them die.
Speaker 1: As far as vaccine trials go, it was a total disaster.
Speaker 1: It's a cruel irony of vaccine development that those two
Speaker 1: kids deaths fifty years ago indirectly led to one of
Speaker 1: the greatest successes in the history of modern drugs. The
Speaker 1: COVID nineteen vaccines, the single biggest breakthrough in coronavirus vaccine research,
Speaker 1: was inspired by scientists who wanted to protect kids from RSV,
Speaker 1: and because of that work, they figured out how to
Speaker 1: make a vaccine for coronavirus two years before the first
Speaker 1: case of COVID nineteen. In this episode, we're going to
Speaker 1: get a little technical on you, but it's necessary in
Speaker 1: order to get to the heart of how these vaccines work.
Speaker 1: From iHeartRadio and School of Humans, I'm Sean Revive and
Speaker 1: this is long shot. Yeah, people want, you know, they
Speaker 1: want to see smoking vessels of like Purvalla, but you know,
Speaker 1: by all just for not chemists. That's Jason McClellan. He
Speaker 1: works at the University of Texas in Austin, and he's
Speaker 1: telling us that his office isn't as exciting as visitors
Speaker 1: might think. I mean, when people come to visit, we
Speaker 1: add food, gallering and things because they want to see yellow.
Speaker 1: But like everything the work of his water, it's like biological.
Speaker 1: I'm in Austin, Texas, at the University of Texas. I'm
Speaker 1: in one of the departments called a Molecular Biosciences department.
Speaker 1: I'm a structural biologist. Structural biologists zoom a way in
Speaker 1: on large molecules or groups of molecules and figure out
Speaker 1: how their parts are put together and why they work
Speaker 1: the way they do. They spend a lot of time
Speaker 1: looking at proteins, which play a ton of roles in
Speaker 1: the body of humans and other living things. Proteins help
Speaker 1: you grow, digest food, fight disease, stay energized. They also
Speaker 1: help bind cells together and transport nutrients. Some hormones like insulin,
Speaker 1: are proteins. Antibodies are proteins, Enzymes are proteins. Hemoglobin, which
Speaker 1: is the dominant component of our blood, is a protein.
Speaker 1: Structural biologists like Jason want to know exactly what proteins
Speaker 1: look like. Without the structures, we don't really know what
Speaker 1: these proteins look like. We draw them as ovals or squares.
Speaker 1: But once we determine their structures, we're able to like
Speaker 1: three D print the actual molecule essentially and know where
Speaker 1: every amino acids is located on the protein, how the
Speaker 1: proteins fold The structure leads to function. So by understanding
Speaker 1: the structure, we know something about how the protein works.
Speaker 1: And if you know how proteins work and how they look.
Speaker 1: You can figure out ways to alter them, change amino acids,
Speaker 1: maybe make the protein more stable, or chop off some parts.
Speaker 1: We don't want to try to make them the best
Speaker 1: possible vaccine antigens. Understanding what specific proteins do is the
Speaker 1: key to the COVID vaccines. But it's not like Jason
Speaker 1: went to college and majored in proteins. Oh, it was
Speaker 1: a kind of winding path, I guess. I went to
Speaker 1: college Wayne State University in Detroit, Michigan. I wanted to
Speaker 1: do pre med and be a doctor. Most I was
Speaker 1: just trying to think of things I could do to
Speaker 1: help people. But early on I realized I really liked chemistry.
Speaker 1: Was quick good at chemistry, so I went to graduate school.
Speaker 1: I've learned a technique called X ray crystallography, and that's
Speaker 1: one of the methods for determining structures of proteins. But
Speaker 1: ultimately I wanted to do a bit more than just
Speaker 1: determine destructures. I wanted to try to have some applied
Speaker 1: research to create things that could end up going into
Speaker 1: humans and improve human health. Around two thousand and eight,
Speaker 1: Jason heard about a guy at the NIH doing a
Speaker 1: lot of cool stuff with HIV, looking closely at the
Speaker 1: virus's structure and trying to design a vaccine. He joined
Speaker 1: the lab there, and while at the NAH he ended
Speaker 1: up working with a doctor and virologist named Barney Graham,
Speaker 1: a world expert on RSV. The RSV vaccine that failed
Speaker 1: back the sixties was made by weakening a strain of
Speaker 1: the virus by passing it through animal tissue or human cells.
Speaker 1: That's the way the great vaccine creators of the past,
Speaker 1: like Maurice Hilleman made their vaccines. Jason and doctor Graham
Speaker 1: wanted to create a vaccine in a totally different way.
Speaker 1: They wanted to manipulate a specific protein of the RSV virus,
Speaker 1: the one the virus uses to infect human cells. It's
Speaker 1: called the f protein f as in fudge, and it
Speaker 1: comes in two forms or a scientists say two confirmations,
Speaker 1: prefusion and post fusion. Here's Jason to explain more. Proteins
Speaker 1: exist in some initial confirmation on the surface of the virus.
Speaker 1: That's what we call the prefusion confirmation. Then there's an
Speaker 1: event that causes the protein to begin refolding and rearranging,
Speaker 1: much like a transformer, going from a car to a robot.
Speaker 1: Parts of it, parts of the protein, just start moving
Speaker 1: and refolding, and it ends up forming an intermediate confirmation
Speaker 1: where it's part of the protein into our host cell membrane.
Speaker 1: That's pretty confusing, so let's try and visualize it. There's
Speaker 1: a virus cell and a human cell. We'll picture them
Speaker 1: as tennis balls. The virus tennis ball has its protein
Speaker 1: on its surface, sort of shape like a cone or
Speaker 1: a stubby mushroom stalk. That's its f protein. So the
Speaker 1: virus tennis ball looks for human tennis balls in the body,
Speaker 1: and when it finds one, here's what happens. The mushroom
Speaker 1: stalk stretches and elongates and attaches itself to the human
Speaker 1: tennis ball. So it's like a bridge between the two
Speaker 1: tennis balls, human and virus. So it's stock between the
Speaker 1: host cell membrane and the viral membrane. The membrane of
Speaker 1: a cell is like its skin. It separates the inside
Speaker 1: of the cell from whatever is on the outside, and
Speaker 1: then it bends back around like a hairpin to bring
Speaker 1: the two membranes together, and then it adopts this final
Speaker 1: state called the postfusion state. So after the stock on
Speaker 1: the virus tennis ball has elongated and attached itself to
Speaker 1: the human tennis ball, it folds itself in half in
Speaker 1: order to bring the two tennis balls together. That's the fusion.
Speaker 1: And so when the f protein has already elongated and
Speaker 1: then folded, it's in its postfusion form. By then it's
Speaker 1: too late. You want to teach your body to fight
Speaker 1: the prefusion form before the mushroom stock has folded and
Speaker 1: attached to the human cell. And so, if you think
Speaker 1: of your immune system as a security guard, you want
Speaker 1: to train your immune system to recognize the form that
Speaker 1: might impact you, like the dangerous form, and that's the
Speaker 1: prefusion form. If you train it to recognize the postfusion form,
Speaker 1: the prefusion form can still sneak by you. So in
Speaker 1: order to train the immune system to recognize the prefusion
Speaker 1: form of rsv F proteins, Jason needed to keep the
Speaker 1: proteins in their prefusion unfolded form. But that isn't easy.
Speaker 1: First of all, rsv F proteins really want to go
Speaker 1: into their post fusion form. Second, proteins are tiny. It's
Speaker 1: not like they could go in with tweezers and hold
Speaker 1: the F protein in place. The F protein has a
Speaker 1: molecular mass of fifty seven point four kilo daltons, which
Speaker 1: means it's weight in Grahams has twenty one zeros. After
Speaker 1: the decimal point, it's really difficult to see what they
Speaker 1: look like, much less alter their behavior. And nobody could
Speaker 1: figure out how do we create a form of the
Speaker 1: prefusion molecule that will stay in the prefusion shape and
Speaker 1: allow us to purify it and inject it into evil.
Speaker 1: But in twenty thirteen they had a breakthrough. They were
Speaker 1: finally able to determine the exact structure of the prefusion
Speaker 1: form of the rsv F protein. Plus they figured out
Speaker 1: how to keep it in that form, how to keep
Speaker 1: it from elongating, and we could start making changes like
Speaker 1: adding in little molecular staples to link two regions together
Speaker 1: so that we the one part couldn't pull away from
Speaker 1: the other. And that work. We were eventually able to
Speaker 1: make four different changes to the protein that really locked
Speaker 1: it in the prefusion confirmation and allowed its use as
Speaker 1: a vaccine antigen. Basically, they discovered how a sort of
Speaker 1: staple the mushroom stock in place, and when Barney immunized
Speaker 1: mice and compared postfusion versus prefusion, the mice receiving the
Speaker 1: prefusion form of the F protein elicited neutralizing antibodies about
Speaker 1: ten times higher than those that received the postfusion This
Speaker 1: is huge. This was the first time structural biology had
Speaker 1: helped discover a new way to stop a virus. Science
Speaker 1: magazine called it one of the top ten breakthroughs of
Speaker 1: twenty thirteen, and their success in stabilizing the F protein
Speaker 1: made them want to try the same process with other
Speaker 1: similar viruses. What else could we take this new approach,
Speaker 1: the structure based approach, and apply to what other pathogens
Speaker 1: are important? And that was around the time that the
Speaker 1: MIRS coronavirus had emerged in the Saudi Arabia and the
Speaker 1: Middle East. That's Middle East respiratory syndrome, which is caused
Speaker 1: by a coronavirus called MRS Covey. The disease was first
Speaker 1: reported in Saudi Arabia in twenty twelve. It causes bad
Speaker 1: respiratory illness, fever, cough, shortness of breath, and it can
Speaker 1: eventually kill you with pneumonia and kidney failure. Even today,
Speaker 1: there are still cases that pop up on occasion. Thirty
Speaker 1: five percent of people infected with it were dying. It's
Speaker 1: a real lethal virus, and we thought that this would
Speaker 1: be a good target to try to take everything we
Speaker 1: had just learned about RSV and apply it to not
Speaker 1: just mers, but coronaviruses in general, because we knew Stars
Speaker 1: coronavirus had emerged in China in two thousand and two
Speaker 1: and it caused an epidemic. Remember Eddie Holmes spoke about
Speaker 1: the First Stars in episode one. I realized is that
Speaker 1: raccoon dogs. They were implicated in the First Stars I
Speaker 1: break of two thousand and two two thousand and three
Speaker 1: because they were positive. First came Stars one, then came
Speaker 1: Mrs Here's Jason again, and then ten years later we
Speaker 1: saw Mirrors emerge. We felt like maybe we were on
Speaker 1: a ten year cycle or something where we keep having
Speaker 1: coronaviruses emerge into the human population, and so we wanted
Speaker 1: to figure out how can we do structure based vaccine
Speaker 1: design or coronaviruses to make the best possible vaccine antigens.
Speaker 1: Jason and Barney Graham wanted to use their ability to
Speaker 1: zoom in on viruses and their ability to play around
Speaker 1: with them to make better vaccines. Since Mrs Covey was
Speaker 1: on their radar, they focus on that virus MERS has
Speaker 1: a protein very similar to the F protein of RSV.
Speaker 1: It's called the spike protein. The spike protein acts pretty
Speaker 1: similarly to the F protein, it just has this additional part.
Speaker 1: If you're thinking about the F protein as a mushroom stock,
Speaker 1: the spike protein is kind of like a full mushroom
Speaker 1: with a cap. When attacking a human cell, the cap
Speaker 1: of the spike protein binds to a certain enzyme on
Speaker 1: the surface of the human cell. The enzyme is called
Speaker 1: the ACE two receptor. The ACE two receptor sort of
Speaker 1: pops off the spike protein's cap, and then the spike
Speaker 1: protein stalk does all the things the F protein does.
Speaker 1: Based on decades of literature, for many researchers, it was
Speaker 1: clear that the spike protein is a key component of
Speaker 1: any vaccine because when humans are infected with coronaviruses, they
Speaker 1: make a large antibody response to the spike protein because
Speaker 1: it's really that that's the major protein on the surface
Speaker 1: of the of the virus. So we know we needed
Speaker 1: to use spike protein as the vaccine but we also
Speaker 1: know that the spike protein can change shapes and isn't
Speaker 1: so stable, so then you know what form do you
Speaker 1: want to use. Our previous work, it's shown that what
Speaker 1: you really want to immunize with is a prefusion stabilized
Speaker 1: form that that can't change shape. So that way we
Speaker 1: train our immune system to recognize the shape of the
Speaker 1: spike protein as it exists on the surface of the virus.
Speaker 1: So with coronavirus, they knew they wanted to stabilize the
Speaker 1: spike protein, the key protein on its surface. They wanted
Speaker 1: to make sure it did not elongate. The spike protein
Speaker 1: was pretty unstable. Its stock was liable to elongate and
Speaker 1: go to post fusion form on the drop of a dime,
Speaker 1: and they had trouble even seeing its structure. To make
Speaker 1: it easier, they switched to another virus, one that we've
Speaker 1: all gotten, HKU one. That's one of the four coronaviruses
Speaker 1: that we've probably all been infected with. It's one of
Speaker 1: the many causes of the common cold. And for whatever reason,
Speaker 1: the spike protein from HK one was actually pretty stable
Speaker 1: and it was amenable to the structured determination efforts, and
Speaker 1: we brought in another group, doctor Andrew Ward's group at
Speaker 1: the Script's Research Institute. He's an expert in cryoelectron microscopy,
Speaker 1: and working together they were able to get that first
Speaker 1: structure of a human coronavirus spike protein in the prefusion shapes.
Speaker 1: Now we had our first blueprint to start making changes
Speaker 1: tweaks to stabilize spike proteins of coronaviruses. Using this blueprint,
Speaker 1: Jason's post duc Nian Chung Wang look closely at the
Speaker 1: mirror structure here, he is, it's actually pretty boy, but
Speaker 1: it's also increasing. Why is it boring and why is
Speaker 1: it interesting? Is that we got to try okay and
Speaker 1: again most of the time it's got to feel yeah,
Speaker 1: it's not that too easy. Nianshuang tested more than one
Speaker 1: hundred different mutations to the spike protein until finally coming
Speaker 1: across two changes that stabilized it, that kept the spike
Speaker 1: in its pre fusion form, and it was really stable.
Speaker 1: It stayed all in the pre fusion shape. What was
Speaker 1: exciting is that the region where we made these changes
Speaker 1: is very similar between different coronavirus spikes, So the same
Speaker 1: changes we could also introduce them into stars. Kobe from
Speaker 1: two thousand and two, and that led to stabilization. So
Speaker 1: my twenty seventeen we really had this method, kind of
Speaker 1: a universal method for stabilizing data coronavirus spikes in their
Speaker 1: prefusion confirmation. But there was one problem with their success
Speaker 1: stabilizing the MERS spike protein. Nobody really cared. It flew
Speaker 1: away under the radar because by then it was evident
Speaker 1: that MERS, as dangerous as it was, didn't spread very easily.
Speaker 1: A few people were getting MERS a vaccine for it
Speaker 1: didn't seem super important. Yeah, it's kind of painful. At
Speaker 1: that time, most coronavirus at that time was not considered
Speaker 1: a big issue because there are few our cases, so
Speaker 1: people didn't pay matt attention on that kind of coronavirus.
Speaker 1: Although their work didn't get much attention, they knew they
Speaker 1: had a vaccine technology ready to be put into action.
Speaker 1: By twenty seventeen, they were prepared to test their stabilizing
Speaker 1: spike protein method on another coronavirus. They just needed an outbreak.
Speaker 1: And then two years later we found out in the
Speaker 1: beginning of twenty twenty that this new virus that was
Speaker 1: causing pneumonia outbreaks in Wuhan China was a coronavirus and
Speaker 1: very similar to Stars Kobe Ie. They'd finally have a
Speaker 1: chance to test out the spike protein in real life,
Speaker 1: but a big question remained, would it work in people.
Speaker 1: Jason and his team spent years figuring out how to
Speaker 1: keep a spike protein stable and use that to make
Speaker 1: a new kind of vaccine, but they needed an outbreak
Speaker 1: to test it on real people infected by a coronavirus.
Speaker 1: Then all of a sudden, they have a real time
Speaker 1: pandemic crashing down on the world. The reports were coming
Speaker 1: out of these pneumonia clusters in Wuhan. We could just
Speaker 1: see it following along on science, Twitter and on the news,
Speaker 1: and so people were already kind of nervous, especially in
Speaker 1: the coronavirus feel that we could be looking at the
Speaker 1: beginnings of a coronavirus outbreak. And then it was early
Speaker 1: in January when it was learned that in fact, it
Speaker 1: is a coronavirus, a beta coronavirus that's similar to the
Speaker 1: first Stars Kobe from two thousand and two. At this point,
Speaker 1: Jason's working at the University of Texas and he's on
Speaker 1: vacation with his family. Barney Graham called me. He said
Speaker 1: he was in contact with the US CDC Chinese CDC.
Speaker 1: They were going to try and work quickly work with Maderna.
Speaker 1: Maderna was then an upstart company based in Cambridge, Massachusetts
Speaker 1: that had never brought a vaccine to market, but they
Speaker 1: tested several vaccines for other viruses, and Barney Graham had
Speaker 1: a plan to work with them on a bat born
Speaker 1: virus called NIPA, but when the novel coronavirus came along,
Speaker 1: doctor Graham told Maderna they should focus on that instead,
Speaker 1: and he wanted to know if we were interested in
Speaker 1: continuing our collaboration to determine the structure of the stars
Speaker 1: Kobe to spike protein and use that information to create
Speaker 1: the vaccine antigens. Jason texted his graduate student Daniel Rapp
Speaker 1: and told him they were going to be busy the
Speaker 1: next few days. Based on this information, we were sort
Speaker 1: of ready to go. That's Daniel, because we've been studying
Speaker 1: these spike proteins for such a long time. We knew
Speaker 1: how to effectively stabilize spike in the pre fusion confirmation
Speaker 1: and that acts as a really good vaccine candidate, and
Speaker 1: so during that time we were kind of just like
Speaker 1: sitting on our hands, like really anxiously waiting for that
Speaker 1: information to become available to everybody, because that was the
Speaker 1: thing that was holding us back from getting started back
Speaker 1: to Jason, and then we just kind of had to
Speaker 1: wait a couple of these because nothing we could really
Speaker 1: do until the genome sequence became available so we could
Speaker 1: see what the sequence of this spike protein was. On
Speaker 1: January eleventh, a scientist in China made it available for all.
Speaker 1: That was John jen Jang who sent the sequence to
Speaker 1: Eddie Holmes in Australia, who then posted it online. Jason
Speaker 1: got the sequence and started working on a vaccine with
Speaker 1: his team the next day. So what does it actually
Speaker 1: mean to get a virus's genetic sequence. The sequence is
Speaker 1: kind of like it's barcode. You're scanning the letters in
Speaker 1: its genome to figure out actually what it is and
Speaker 1: how it works. It's essentially a file like somebody can
Speaker 1: just you know, it's an attachment, the text file that
Speaker 1: somebody can send us containing the sequence, just a bunch
Speaker 1: of letters, so like computer code. And then we have
Speaker 1: to figure out what changes we want to make very
Speaker 1: quickly just by taking that sequence and aligning it to
Speaker 1: the other spike sequences. We knew right where to put
Speaker 1: the two changes that we had identified earlier, so that
Speaker 1: was probably done within a couple of hours. Just the
Speaker 1: design of these constructs. Remember, Jason's team is looking for
Speaker 1: a way to alter the proteins on the surface of
Speaker 1: the virus so they won't go into that post fusion confirmation.
Speaker 1: The change that Niche Wong and the team had discovered
Speaker 1: working with mers is called the two P mutation. The
Speaker 1: P stands for prolene, one of twenty amino acids that
Speaker 1: are the building blocks of all living things. Proleins are
Speaker 1: special because they're the most rigid amino acid and because
Speaker 1: they are rigid. Swapping out two other amino acids for
Speaker 1: two proteins at a certain joint of the spike protein
Speaker 1: keeps the mushroom stock in place, meaning it keeps it
Speaker 1: in pre fusion form. But Jason and his team couldn't
Speaker 1: just do the two P mutation on the laptop. They
Speaker 1: had to do it in real life. There are companies
Speaker 1: out there that can take a modified genetic sequence like
Speaker 1: the one they designed at UT and turn it into
Speaker 1: something physical. And you need to turn it into a
Speaker 1: biological substance. Like actual DNA. And so that's where we
Speaker 1: need to work with the companies, where we send them
Speaker 1: the file and they're able to synthesize DNA and send
Speaker 1: it send it back to us, and then we have
Speaker 1: to stitch some of it together and do some other things.
Speaker 1: And so in the lab we were working with the DNA.
Speaker 1: When Jason says he's working with DNA, he essentially means
Speaker 1: that they're making changes to genes in order to program
Speaker 1: human cells to produce the stable spike proteins. Remember this
Speaker 1: is the key to the whole vaccine. Our own cells
Speaker 1: will be the factories that produce the stable spike proteins,
Speaker 1: and the DNA is the thing sending those instructions via
Speaker 1: messenger RNA. So that way the cells realized the instructions
Speaker 1: have changed, the recipe has changed, if you will, and
Speaker 1: they just make a protein containing proteins at those positions
Speaker 1: instead of the original amino acids at those positions. I
Speaker 1: think within ten days, maybe a bit more, Nianchwang had
Speaker 1: had cloned like ten different plasmids. Plasmids are like small
Speaker 1: snippets of DNA molecules, ending Chwang was working around the
Speaker 1: clock to stitch them together. Into a full DNA strand
Speaker 1: that could encode for the spike proteins. Meanwhile, Barney Graham's
Speaker 1: lab was talking to MODERNA telling them how to stabilize
Speaker 1: the spike protein with a two P mutations, like what
Speaker 1: spike protein to encode in the mRNA, where to put
Speaker 1: the stabilizing prolein mutations. Then came January thirtieth, twenty twenty.
Speaker 1: It was an exciting day. We Daniel was harvesting. He's
Speaker 1: talking about his grad student, Daniel Repp, the purified spike
Speaker 1: proteins that were produced by the cells we had growing
Speaker 1: in the lab. So we was able to harvest the spike,
Speaker 1: purify it and start freezing cryoEM grids. cryoEM stands for
Speaker 1: cryoelectron microscopy, a method for seeing proteins at atomic resolution. First,
Speaker 1: Daniel would flash freeze the proteins in ice on a
Speaker 1: tiny mesh disc. Then he'd use an electron microscope to
Speaker 1: take thousands of two dimensional images of the proteins. A
Speaker 1: computer program then use those pictures to create a three
Speaker 1: D image showing the structure of the proteins. That allowed
Speaker 1: us to start the data collection that night, and we
Speaker 1: could see the individual spike proteins for the first time,
Speaker 1: and within twenty four hours we had collected a complete
Speaker 1: data set and we got the first looks at the
Speaker 1: molecular shape of the coronavirus spike protein. Within about thirty
Speaker 1: days we had determined in a manuscript submitted that paper
Speaker 1: has been sighted close to four thousand times now we have.
Speaker 1: We were sharing the coordinates of the structure, the blueprint
Speaker 1: of the structure to people all over the world. We
Speaker 1: were shipping the plasmids that we had made two hundred
Speaker 1: groups or so. Is that way they could make the
Speaker 1: spike protein in their labs for diagnostics, for antibody isolation
Speaker 1: or additional structural studies. So it is a really crazy
Speaker 1: time early last year. Now they knew exactly how to
Speaker 1: stabilize the spike protein the mushroom shape on the surface
Speaker 1: of the coronavirus. They'd actually created stabilized spikes in the lab,
Speaker 1: and the pharmaceutical company Baderna would use these stabilize spikes
Speaker 1: as building blocks for the vaccine. They are just directly
Speaker 1: synthesizing the mRNA, but it's still at the instructions level,
Speaker 1: such that when the RNA is injected into a person
Speaker 1: that person sells read the recipe and make a protein
Speaker 1: that contains two proteins at these positions rather than the
Speaker 1: other amino acids that the virus normally uses. RNA is
Speaker 1: the sort of middleman between DNA and the spike proteins.
Speaker 1: We'll learn more about this in the next episode, but
Speaker 1: the saying amongst scientists is that DNA makes RNA, makes
Speaker 1: proteins makes life. Maderna's vaccine sort of skips the DNA
Speaker 1: step and sends the mRNA or messenger RNA directly into
Speaker 1: the body. Maderna encapsulates the mRNA in a fatty sphere
Speaker 1: called a lipid nanoparticle. Another thing we'll talk about in
Speaker 1: an upcoming episode. That bubble helps the mRNA get to
Speaker 1: ourselves without falling apart, and when it does, our selves
Speaker 1: get the recipe from making two p mutated spike proteins.
Speaker 1: They make them, and the immune system sees these coronavirus
Speaker 1: proteins in their prefusion form, and the immune system learns
Speaker 1: that they are a threat. It learns that a spike
Speaker 1: protein in the folded hairpin shape is an enemy and
Speaker 1: the body has to fight it and stop it from spreading.
Speaker 1: If you get infected with coronavirus. The body now knows
Speaker 1: what to do when it comes across the spike protein
Speaker 1: in pre fusion form. It knows how to keep you
Speaker 1: from getting sick. They tested the vaccine in mice and
Speaker 1: saw that it produced an antibody response, and then they
Speaker 1: readied it for humans. By March twenty twenty, Maderna had
Speaker 1: enough vaccine to be used for a phase one clinical trial.
Speaker 1: That material was shipped to the different sites in the
Speaker 1: US where they began immunizing the first forty five people
Speaker 1: with different doses, testing side effects, dose response, the level
Speaker 1: of antibodies being produced. Yeah, I think it's like it's
Speaker 1: like sixty three days or sixty five days something. After
Speaker 1: the genome sequence was made available online, the first people
Speaker 1: are being immunized, which is incredible. Um. Hi, my name
Speaker 1: is Nicolas Nicola in the second episode was one of
Speaker 1: those first people. I was part of the Phase one
Speaker 1: of modernas vaccine trial for COVID. Feisser and Johnson and
Speaker 1: Johnson also used the two P mutation for their COVID vaccines.
Speaker 1: It's the driving force behind all the vaccines that Americans
Speaker 1: are getting and of some other vaccines being made around
Speaker 1: the world. The last year is difficult because there's a
Speaker 1: lot of mixed emotions because there are certain scientific successes
Speaker 1: that we would normally celebrate, but the whole time the
Speaker 1: economy is being devastated. People are losing their jobs, hospitalizations, deaths.
Speaker 1: So it's really a range of mixed emotions where we're
Speaker 1: excited for the science and everything we've been working on
Speaker 1: for years being translated into a vaccine that was looking
Speaker 1: very promising, but at the same time also just really devastating.
Speaker 1: We spoke with Jason in March of this year. At
Speaker 1: the time, three vaccines were already approved for emergency use
Speaker 1: by the FDA, More than thirty million Americans had already
Speaker 1: been fully vaccinated, and millions more were scrambling for appointments.
Speaker 1: Me and my producer Gabby had gotten the Maderna shot
Speaker 1: a few days earlier, but Jason still hadn't been vaccinated.
Speaker 1: He was young and healthy, not a frontline worker, happy
Speaker 1: to wait his turn. He got his first shot a
Speaker 1: couple of weeks later. The search for an RSV vaccine
Speaker 1: after that trial went bad in the sixties inspired the
Speaker 1: technology used in today's COVID vaccines. But what about RSV
Speaker 1: that virus that still kills thousands of people every year.
Speaker 1: It's normally a virus that peaks in winter, but it's
Speaker 1: been surging in children this summer alongside of and maybe
Speaker 1: even because of the surge in the coronavirus delta variants.
Speaker 1: There's still no vaccine for RSV on the market, but
Speaker 1: they're working on it. Last year November October of twenty twenty,
Speaker 1: prefusion f proteins have gone into phase three clinical trials,
Speaker 1: and yeah, we're really excited about that. It's taken a
Speaker 1: long time, that's sort of the normal vaccine development timelines,
Speaker 1: starting a thirteen with the antigen just entering phase three
Speaker 1: clinical trials in twenty twenty, but yeah, everything still looks
Speaker 1: really good and we're really excited by it. Scientific failure
Speaker 1: and scientific success are unstable concepts, about as unstable as
Speaker 1: prefusion spike proteins. When a trial for an RSV vaccine
Speaker 1: failed about as badly as a vaccine trial can fail,
Speaker 1: it led to a newer and better way of making vaccines.
Speaker 1: Fifty years later in twenty seventeen, when they stabilize the
Speaker 1: spike protein, Jason and Nichuang and Daniel and everyone else
Speaker 1: they worked with. All they got was crickets, but they
Speaker 1: did it anyway. Here's Daniel Rapagin. Yeah, it's it's a
Speaker 1: little surreal because we would be doing this work whether
Speaker 1: or not COVID nineteen became a pandemic. We would still
Speaker 1: be studying the spike protein figuring out how it worked.
Speaker 1: But it's been a little surreal to have so much
Speaker 1: attention paid to our work because, like as I've been
Speaker 1: describing to you, we do things that most people would
Speaker 1: think of is just like minutia, Like if there wasn't
Speaker 1: a pandemic, we would still be doing this and people
Speaker 1: would wonder why. The best example of it is, for
Speaker 1: the past like five or six years, I've been telling
Speaker 1: people I studied coronaviruses, and up until like a year ago,
Speaker 1: people would say, what's a coronavirus. On the next episode
Speaker 1: of long Shot, we'll speak with the founders of Moderna,
Speaker 1: a company that started with essentially zero employees before becoming
Speaker 1: one of the biggest names in COVID nineteen vaccines. We'll
Speaker 1: also find out what role Jennifer Aniston played in that
Speaker 1: origin story. Today's episode of long Shot was produced, written,
Speaker 1: and narrated by me Sean Revie. My co producer is
Speaker 1: Gabby Watts. Special thanks to Noel Brown and iHeartRadio and
Speaker 1: journalist Alan Dove and Ryan Cross. Executive producers are Virginia Prescott,
Speaker 1: Brandon Barr and Else Crowley. Long Shot was scored by
Speaker 1: Jason Shannon. The score was mixed by Vic Stafford. Sound
Speaker 1: design and audio mix was by Harper Harris with Tunewelder
Speaker 1: School of Humans