September 29, 2021 • 21 mins
The future of coronavirus vaccines may be an engineered spike protein called HexaPro. And it's carried into the human body by a bird disease. We'll learn how it works, and ask why one of this vaccine's creators brought the 1918 flu back from the dead.
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Episode Transcript
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Speaker 1 (00:08):
School of Humans. Let's go back to the spike protein.
Remember Jason McClellan, the guy at the University of Texas
who told us about the spike protein in episode four.
It's the mushroom stock shaped thing on coronavirus cells. Based
on decades of literature many researchers, it was clear that
the spike protein is a key component of any vaccine
(00:31):
because Jason explained how the spike protein is, how the
coronavirus attaches itself to human cells and infects us with
the virus, and why we need to teach the immune
system to recognize it. And that's how the Maderna Adviser
and Johnson and Johnson vaccines work. All the vaccines Americans
are getting, but there are some big problems with those vaccines.
(00:53):
Not in their function. They work incredibly well and protecting
us from COVID, but they're expensive. Expensive because they're made
by giant pharmaceutical companies designed to make money. Expensive because
they require relatively hard to get ingredients that have to
be put together, and specialized factories with specialized equipment. And
expensive is fine for America. It's kind of okay that
(01:16):
these pharma companies make lots of money for providing an
invaluable service, and the government is subsidizing the COVID vaccines anyway.
It's that they're free of charge, but expensive doesn't work
for a lot of the world. Expensive means poorer countries
can't get doses because they're outbid or have no money
to bid with. And if we're not protected, unless everyone
is protected, that doesn't stop at the border. It means
(01:40):
the whole world has to be vaccinated, not just the
whole country. But right now that's not happening. I mean,
as of this recording, only two percent of people in
low income countries have gotten even a single dose of
coronavirus vaccine two percent. And so a bunch of people,
including Jason McClellan and its mother, top notch scientists got
(02:00):
together and they created a cheaper COVID nineteen vaccine. In
this episode, we're going to tell the story of how
they did that. From School of Humans and iHeartRadio, I'm
Sean Revive and this is long shot. Okay, hold on
(02:27):
one second, sure, thank you. Yeah. This is Peter Palais.
He's a microbiologist and professor and share of the Department
of Microbiology at the Icon School of medicine and mount Sine.
Just sorry, wind bottling the back. You know that's not
the best of here. Okay, this is what he does
(02:47):
that I have been working for really decades um ourna
viruses with an emphasis on influence of us is over
many many years and there I have written an anti
virals on Vaccines, UM Genetics um the whole gamut. So.
Peter has been working on RNA viruses and especially flu
(03:09):
viruses since the nineteen seventies. He created the first genetic
maps for three of the four types of flu viruses, A, B,
and C, the three important ones as far as humans
are concerned. D is mostly a cattle virus. Peter is
also a pioneer in the field of reverse genetics. He
said technology allows you to make changes in the genome
(03:33):
of the virus. Reverse genetics allows you to make particular
changes in a virus to sort of pick and choose
which genes you want to include or exclude. Reverse genetics
allows researchers to look at a gene, a basic unit
of DNA or RNA, the thing that passes traits from
your parents to you, and discover what it does, what
(03:53):
its purposes, and using reverse genetics Peter was part of
a team that actually brought the nineteen eighteen Spanish flu
back to life, the one that killed maybe fifty million
people three percent of the world back then, and they
did this for science. Peter and a bunch of other
scientists were able to frankenstein the Spanish flu. It started
(04:16):
with a Swedish microbiologist named Johann Houlton. In nineteen fifty one.
He traveled to Alaska to a tiny village called Brevig
Mission to find a mass grave of Spanish flu victims.
In nineteen eighteen, Brevig Mission had only eighty people living there,
and seventy two of them died over a five day
period from the flu. The bodies were buried in permafrost
(04:41):
and marked with white crosses. Holton believes he could find
traces of the virus in the bodies. He got permission
from village elders to unfreeze the grave with campfires and
unearthed several bodies. He took lung tissue from a few
of the dead, including that of a young girl still
wearing a blue dress and red hair ribbons. After all
these years, he tried to preserve the samples during travel
(05:04):
all the way back to his lab at the University
of Iowa, but when he got there, he couldn't extract
any virus from the tissue samples. Half a century later,
he would get another chance. In nineteen ninety seven, he
read about the work of a team at the Armed
Forces Institute of Pathology in DC. They had extracted RNA
(05:27):
from the nineteen eighteen virus from the preserved lung tissue
of a US service member, but the sample didn't contain
enough virus to collect a full genetic sequence. Holton reached
out to the team and offered to go back to
the Alaskan village he'd gone to forty six years earlier
and find more samples. He did, and this time he
was able to successfully preserve the lung tissue on the
(05:49):
way back from brevig mission using the samples Holton collected,
along with samples from two long dead US soldiers, the
Armed Forces Institute of Pathology researchers had the nineteen eighteen
flu fully sequenced a few years later, so they had
the code to build it, like having a blueprint for
a house before construction, but the virus still needed to
(06:11):
be built. That's where Peter Palais came into it. They
brought in Peter and his colleagues at Mount Sinai to
create the parts that would be put together in a
highly secured CDC lab to recreate the nineteen eighteen virus
using Peter's reverse genetics techniques in two thousand and five,
working alone during off hours when nobody else was in
(06:32):
the lab to be extra safe in case of contamination,
microbiologist Terence Tumpy made the Spanish flu virus unextinct. The
Franken virus lived. Tumpy then performed experiments on mice comparing
the lethality of the nineteen eighteen virus to more modern
day flues. The old flu was found to be at
(06:54):
least one hundred times more deadly than the other flu
viruses he tested against. But what if the actual nineteen
eighteen flu got out of the lab, would we be
in for more years of quarantine? And why is it
important to study a virus that hasn't been out there
in almost one hundred years? What was the goal of that?
To understand? I mean the first one was it? So
we have anti virls against influence of ours. These are
(07:16):
the famous humidities inhibitors, tamiflu Baloques Ofvere et cetera. And
that was the first thing we want to know. Can
the available FDA prooved thugs, can the inhibit the virus?
And we were thank the Lord. We were very happy
to see right away that these virus has behaved like
any other influence of ours. Also, we learned that it
(07:38):
is inhibitable by anti virus, It is not resisting to vaccines.
We've learned how it gets transmitted, and we have a
much better understanding of the nineteen eighteen virus than we
had before. And I can honestly say, if that virus,
the nineteen eighteen virus would emerge miraculously, I don't think
(07:58):
it will, we would be not as helpless as we
were a hundred years ago. And a lot has to
do with our understanding now with the whole alimentarium of
things which would prevent such a pandemic. Again, reverse genetics,
the field that Peter Palaze helped create, has also proven
(08:21):
valuable in creating new vaccines. Many vaccines today are developed
by making genetic changes to a virus so they're less pathogenic,
less able to make you sick, but the less pathogenic
virus remains recognizable to the immune system so that it
can learn to fight off the real virus when it
enters the body. One type of vaccine that works this
(08:43):
way is called a viral vector vaccine. These are vaccines
that use one virus as a delivery method or vector
to send instructions to the body to fight off another virus.
The Astrazenica and Johnson and Johnson vaccines are viral vector vaccines.
The Russian Sputnik vaccine, that has been given emergency authorization
in more than seventy countries, is also a viral vector vaccine.
(09:07):
Now Peter has been involved in a new viral vector
vaccine for COVID nineteen. But before we get there, we
got to go back to spike proteins and chickens. Let's
refresh our memory a bit more on the spike protein.
The way the American vaccines work is by showing the
immune system stabilize spike proteins, which the body then learns
(09:31):
to recognize when coronavirus cells enter the body. The way
the spike proteins and the vaccines are stabilized is by
swapping out two amino acids for two prolleins. Really stable
amino acids at a specific joint. That's called the two
P mutation. The P is for prolins. That's what the
vaccines use to teach the body to protect against coronavirus.
(09:55):
And after figuring this out, Jason McClellan at UT didn't
stop there, and in March twenty twenty one, with lots
of trial and error in the lab, he and his
p pole came up with an even better way of
stabilizing the spike protein. It's not that different from the
two P mutation, but this one involves using six pro
lieins to stabilize the spike. In this case, using six
(10:18):
is better than two. They name the stabilized spike protein
hexapro because of the six prolleins. Hexa means six. Jason's
hope was that hexapro could be the basis for the
next generation of COVID vaccines, and the University of Texas
arranged it so that hexapro could be used royalty free
(10:39):
by low and middle income countries. That means these countries
can theoretically make vaccines cheaply, but first they needed an
inexpensive way to get the super stabilized protein into the body.
At the same time that Jason McClellan was working on hexapro.
An organization called PATH was trying to figure out a
way to deliver more vaccines to poorer countries. Were extremely
(11:03):
interested in ensuring at countries where health budgets are not
strong have access to world class vaccines that are life saving,
on the proposition that everyone deserves to have access to
life saving vaccines. That's doctor Bruce Innes. He's a physician
and he's been working on vaccines for almost forty years,
(11:26):
tons of them against human papaloma virus, against rotavirus, gastroenteritis,
various cella vaccine, combination, measles, MOBSTERB varius cella vaccine, influenza viruses,
human papaloma virus. Bruce has been a PATH for five years.
The organization is based in Seattle and aims to improve
(11:48):
public health in lower income countries through innovation and partnerships.
At PATH, Bruce has worked on vaccines against RSV, meningitis, pneumonia, flu,
and now COVID. We realize that with COVID nineteen, even
early in the PATH demic, that no one would be
safe until everyone was safe, and that's why it was
(12:10):
important for us to think about in showing that all
countries would have access equitable access to covid vaccines. This
is where chickens come back into it. Remember an episode
three when we heard from the King of all vaccine inventors,
Maurice Hilliman. He grew up raising chickens on the family
farm and talked about how important they were to his
(12:32):
work in the lab years later and my career, chickens
were my best friend because I used them for so
many types of experimentation, and then we're breakthrough experiments. A
lot of vaccines are grown in chicken eggs, including lots
of the vaccines invented by Hilliman. Bruce and Path had
(12:53):
worked in the past with some middle income countries to
improve their capacity to produce egg based flu vaccines. An
egg based vaccine is literally one where the primary ingredient
the virus to be expressed, is grown and chicken eggs.
That's the most common way to make the flu vaccines
you get or can get every winter. They are really
inexpensive to make, and if you can make a covid
(13:15):
vaccine the same way, then you can theoretically just convert
a flu vaccine factory into a covid vaccine factory, and
we asked Mount Sinai. That is, they asked Peter Plais
and his colleagues at Mount Sinai if there was a
way to make a covid vaccine using a virus that
would replicate in eggs. They said, yes, We've done this
(13:36):
before with an avian virus called Newcastle disease virus virulent.
Newcastle disease or simply Newcastle disease, is an avian disease,
a bird flu. In other words, it can infect humans,
but rarely produce the symptoms in people. The disease is
caused by the appropriately named Newcastle disease virus, and it
(14:00):
spreads from bird to bird through their poop and other
bodily secretions. It's a big problem for commercial chicken factories
that squeeze a lot of chickens into densely packed spaces
amorally in my opinion, but that's neither here nor there.
Newcastle disease can spread on a factory farm and sicken
or kill their chickens. So the commercial chicken companies spray
(14:22):
Newcastle disease vaccines into their factories and vaccinate all the
chickens at once. Here's Peter to give a somewhat apocalyptic
visual in these big, big factories, and Newcastle disease virus
is put in canastus on the back of people and
they go into these factories. In spray life Newcastle disease virus,
(14:45):
chickens can also get flu viruses, and the factories didn't
want them getting that either. So Peter had worked on
a Newcastle disease vaccine that could also stop chickens from
getting the flu. Newcastle disease has also been explored as
a vector for carrying an ebola gene and for carrying
cancer killing viruses. And so we said, okay, why I
don't put the a saus coronavirus spike protein into Newcastle
(15:09):
disease burs And that's what we do at Mount Sinai.
Peter as colleagues, including Fluorine Cramer and Adolpho Garcia Sastre,
engineered a Newcastle disease virus that could carry hexapro into humans.
So the Newcastle disease is the vector for the hexapro
stabilized spike protein. They call the vaccine NDV HXPS NDV
(15:32):
Newcastle Disease Virus h XPS hexapro spike instead of using
super specialized machinery. They're making this vaccine and chicken eggs.
They've made multiple lots of vaccine, initially at pilot scale,
which might involve a few thousand eggs, and we're getting
typically about seven to eight finished vaccine doses per inoculated egg.
(15:55):
You can think of the egg as a mini bioreactor,
each one self contained bioreactor. And now they're in the
process of manufacturing investigational vaccine lots at full commercial scale.
Clinical trials and humans for NDVHXPS are already underway in Vietnam, Thailand,
and Brazil. In Vietnam and Thailand they moved on to
(16:16):
phase two after phase one trials show that the vaccines
are safe and produce an immune response in people. In Thailand,
they're also onto phase two and expect to produce twenty
million or more doses of the vaccine per year starting
in twenty twenty two. Brazil has entered phase one, and
if all three country trials proved successful, they can produce
(16:36):
vaccines fairly quickly since they already have functioning flu vaccine
production facilities. I can't tell you our quick clin Nicola
and animal challenge experience, how compelling. I can't take I
can't protect every mouse and every hamstand the world against
any sauces. It works beautifully in the animal systems we had.
(16:57):
Based on the animal studies, you can feel like it's
a really very good sign, no doubt, no doubt. So
Pete is very confident that the Hexa pro Newcastle hybrid
vaccine will work well in people, and let's hope that
it does. Not only is it really cheap and easy
to produce, there's another benefit to this vaccine. One of
(17:18):
the reasons if fives are in well, the end of
vaccine also expensive. You know what. One of the reasons
is stability. They have to have the binus foody and
minus eighty degree freezers explorinly expensive. All of vaccine is
stable at kitchen refrigeration temperatures two to four degrees four weeks,
so it is very very stable. That's one of the
(17:41):
biggest issues with modern medicine in developing countries. It's not
always possible to keep it cold enough. Ndv HXPS helps
with that a ton by staying stable at refrigerator temperatures,
and the manufacturers that Path is working with can make
a lot of vaccine in big bunches. Here's Bruce. A
(18:02):
typical lot size involves more than five thousand eggs that
are inuculated and harvested three days later. And when I
say innoculated and harvested, you put a small amount of
seed virus into the egg. It propagates in the embryo
when it's incubated at thirty seven degrees. Then the eggs
are chilled overnight at the end of a seventy two
(18:23):
hour period and the egg fluids the whites of the
egg are harvested and from that you can purify the
virus inactivate it formulated for administration. So the Southeast Asian
countries will have a typical lot size of around fifty
to forty to fifty thousand eggs per lot, and each
(18:44):
manufacturer can initiate multiple lots in a given week. Vietnam,
for example, as of this recording, is still instituting a
severe nationwide lockdown because only seven percent of their population
has been able to get fully vaccinated, so being able
to produce their own vaccine would be huge. Is a
(19:05):
middle income country, relatively wealthy by world standards. Seven percent
is high compared to low income countries, which, like I said, earlier,
are only two percent vaccinated. Right now, the US and
other wealthy countries maybe doing okay with vaccination, but we're
doing a shit job as a planet. The Newcastle hexapro
(19:27):
vaccine could help change that. Our aspiration, and we shared
this with the manufacturers, is that this would be one
of the most affordable vaccines possible. The starting material is
an embryonated egg, a fertile egg and a small bit
of seed virus, and the cost of eggs for production
(19:48):
for vaccines is somewhere between twenty five and thirty cents
an egg. And I told you that there's seven to
ten doses per egg, so that's only pennies per dose.
Of course it has to be mixed with a bunch
of other ingredients first, but you can imagine the NDVHXPS
vaccine ends up pretty cheap. If the main thing doing
the work in it only costs a few cents, that's
(20:09):
a good way to get the world vaccinated. This is
a grand experiment. The inactivated Newcastle disease virus vaccine has
never been administered to human subjects before. It's brand new technology.
It's very very exciting, and the preclinical data were astonishing.
We think that the covid pandemic won't abate until everyone
(20:32):
has access to vaccine. There are many countries that have
been left behind. We hope that the ndv hxp S
vaccine will have an important impact on helping to abate
the epidemic and will be used in years to come
for controlling endemic covid disease which is likely to continue
(20:53):
to circulate them on human populations. The next and last
episode of long Shot is going to be a little
different than the others. We're going to go over everything
we've talked about in a series and put it all
together into one story and then fill in some gaps
from the history of vaccines that's next week on long Shot.
(21:17):
Long Shot is a production of School of Humans and iHeartRadio.
Today's episode was produced, written, and narrated by me Sean Revive.
A co producer is Gabby Watts. Special thanks to Noel
Brown and iHeartRadio. Executive producers are Virginia Prescott, Elsie Crowley,
and Brandon Barr. Fact Checking for this episode is by
(21:38):
Adam Shadow. Long Shot was scored by Jason Shannon. The
score was mixed by Vic Stafford. Sound Design and audio
mixed was by Harper Harris with Tunewielders School of Humans
School of Humans. Let's go back to the spike protein.
Remember Jason McClellan, the guy at the University of Texas
who told us about the spike protein in episode four.
It's the mushroom stock shaped thing on coronavirus cells. Based
on decades of literature many researchers, it was clear that
the spike protein is a key component of any vaccine
(00:31):
because Jason explained how the spike protein is, how the
coronavirus attaches itself to human cells and infects us with
the virus, and why we need to teach the immune
system to recognize it. And that's how the Maderna Adviser
and Johnson and Johnson vaccines work. All the vaccines Americans
are getting, but there are some big problems with those vaccines.
(00:53):
Not in their function. They work incredibly well and protecting
us from COVID, but they're expensive. Expensive because they're made
by giant pharmaceutical companies designed to make money. Expensive because
they require relatively hard to get ingredients that have to
be put together, and specialized factories with specialized equipment. And
expensive is fine for America. It's kind of okay that
(01:16):
these pharma companies make lots of money for providing an
invaluable service, and the government is subsidizing the COVID vaccines anyway.
It's that they're free of charge, but expensive doesn't work
for a lot of the world. Expensive means poorer countries
can't get doses because they're outbid or have no money
to bid with. And if we're not protected, unless everyone
is protected, that doesn't stop at the border. It means
(01:40):
the whole world has to be vaccinated, not just the
whole country. But right now that's not happening. I mean,
as of this recording, only two percent of people in
low income countries have gotten even a single dose of
coronavirus vaccine two percent. And so a bunch of people,
including Jason McClellan and its mother, top notch scientists got
(02:00):
together and they created a cheaper COVID nineteen vaccine. In
this episode, we're going to tell the story of how
they did that. From School of Humans and iHeartRadio, I'm
Sean Revive and this is long shot. Okay, hold on
(02:27):
one second, sure, thank you. Yeah. This is Peter Palais.
He's a microbiologist and professor and share of the Department
of Microbiology at the Icon School of medicine and mount Sine.
Just sorry, wind bottling the back. You know that's not
the best of here. Okay, this is what he does
(02:47):
that I have been working for really decades um ourna
viruses with an emphasis on influence of us is over
many many years and there I have written an anti
virals on Vaccines, UM Genetics um the whole gamut. So.
Peter has been working on RNA viruses and especially flu
(03:09):
viruses since the nineteen seventies. He created the first genetic
maps for three of the four types of flu viruses, A, B,
and C, the three important ones as far as humans
are concerned. D is mostly a cattle virus. Peter is
also a pioneer in the field of reverse genetics. He
said technology allows you to make changes in the genome
(03:33):
of the virus. Reverse genetics allows you to make particular
changes in a virus to sort of pick and choose
which genes you want to include or exclude. Reverse genetics
allows researchers to look at a gene, a basic unit
of DNA or RNA, the thing that passes traits from
your parents to you, and discover what it does, what
(03:53):
its purposes, and using reverse genetics Peter was part of
a team that actually brought the nineteen eighteen Spanish flu
back to life, the one that killed maybe fifty million
people three percent of the world back then, and they
did this for science. Peter and a bunch of other
scientists were able to frankenstein the Spanish flu. It started
(04:16):
with a Swedish microbiologist named Johann Houlton. In nineteen fifty one.
He traveled to Alaska to a tiny village called Brevig
Mission to find a mass grave of Spanish flu victims.
In nineteen eighteen, Brevig Mission had only eighty people living there,
and seventy two of them died over a five day
period from the flu. The bodies were buried in permafrost
(04:41):
and marked with white crosses. Holton believes he could find
traces of the virus in the bodies. He got permission
from village elders to unfreeze the grave with campfires and
unearthed several bodies. He took lung tissue from a few
of the dead, including that of a young girl still
wearing a blue dress and red hair ribbons. After all
these years, he tried to preserve the samples during travel
(05:04):
all the way back to his lab at the University
of Iowa, but when he got there, he couldn't extract
any virus from the tissue samples. Half a century later,
he would get another chance. In nineteen ninety seven, he
read about the work of a team at the Armed
Forces Institute of Pathology in DC. They had extracted RNA
(05:27):
from the nineteen eighteen virus from the preserved lung tissue
of a US service member, but the sample didn't contain
enough virus to collect a full genetic sequence. Holton reached
out to the team and offered to go back to
the Alaskan village he'd gone to forty six years earlier
and find more samples. He did, and this time he
was able to successfully preserve the lung tissue on the
(05:49):
way back from brevig mission using the samples Holton collected,
along with samples from two long dead US soldiers, the
Armed Forces Institute of Pathology researchers had the nineteen eighteen
flu fully sequenced a few years later, so they had
the code to build it, like having a blueprint for
a house before construction, but the virus still needed to
(06:11):
be built. That's where Peter Palais came into it. They
brought in Peter and his colleagues at Mount Sinai to
create the parts that would be put together in a
highly secured CDC lab to recreate the nineteen eighteen virus
using Peter's reverse genetics techniques in two thousand and five,
working alone during off hours when nobody else was in
(06:32):
the lab to be extra safe in case of contamination,
microbiologist Terence Tumpy made the Spanish flu virus unextinct. The
Franken virus lived. Tumpy then performed experiments on mice comparing
the lethality of the nineteen eighteen virus to more modern
day flues. The old flu was found to be at
(06:54):
least one hundred times more deadly than the other flu
viruses he tested against. But what if the actual nineteen
eighteen flu got out of the lab, would we be
in for more years of quarantine? And why is it
important to study a virus that hasn't been out there
in almost one hundred years? What was the goal of that?
To understand? I mean the first one was it? So
we have anti virls against influence of ours. These are
(07:16):
the famous humidities inhibitors, tamiflu Baloques Ofvere et cetera. And
that was the first thing we want to know. Can
the available FDA prooved thugs, can the inhibit the virus?
And we were thank the Lord. We were very happy
to see right away that these virus has behaved like
any other influence of ours. Also, we learned that it
(07:38):
is inhibitable by anti virus, It is not resisting to vaccines.
We've learned how it gets transmitted, and we have a
much better understanding of the nineteen eighteen virus than we
had before. And I can honestly say, if that virus,
the nineteen eighteen virus would emerge miraculously, I don't think
(07:58):
it will, we would be not as helpless as we
were a hundred years ago. And a lot has to
do with our understanding now with the whole alimentarium of
things which would prevent such a pandemic. Again, reverse genetics,
the field that Peter Palaze helped create, has also proven
(08:21):
valuable in creating new vaccines. Many vaccines today are developed
by making genetic changes to a virus so they're less pathogenic,
less able to make you sick, but the less pathogenic
virus remains recognizable to the immune system so that it
can learn to fight off the real virus when it
enters the body. One type of vaccine that works this
(08:43):
way is called a viral vector vaccine. These are vaccines
that use one virus as a delivery method or vector
to send instructions to the body to fight off another virus.
The Astrazenica and Johnson and Johnson vaccines are viral vector vaccines.
The Russian Sputnik vaccine, that has been given emergency authorization
in more than seventy countries, is also a viral vector vaccine.
(09:07):
Now Peter has been involved in a new viral vector
vaccine for COVID nineteen. But before we get there, we
got to go back to spike proteins and chickens. Let's
refresh our memory a bit more on the spike protein.
The way the American vaccines work is by showing the
immune system stabilize spike proteins, which the body then learns
(09:31):
to recognize when coronavirus cells enter the body. The way
the spike proteins and the vaccines are stabilized is by
swapping out two amino acids for two prolleins. Really stable
amino acids at a specific joint. That's called the two
P mutation. The P is for prolins. That's what the
vaccines use to teach the body to protect against coronavirus.
(09:55):
And after figuring this out, Jason McClellan at UT didn't
stop there, and in March twenty twenty one, with lots
of trial and error in the lab, he and his
p pole came up with an even better way of
stabilizing the spike protein. It's not that different from the
two P mutation, but this one involves using six pro
lieins to stabilize the spike. In this case, using six
(10:18):
is better than two. They name the stabilized spike protein
hexapro because of the six prolleins. Hexa means six. Jason's
hope was that hexapro could be the basis for the
next generation of COVID vaccines, and the University of Texas
arranged it so that hexapro could be used royalty free
(10:39):
by low and middle income countries. That means these countries
can theoretically make vaccines cheaply, but first they needed an
inexpensive way to get the super stabilized protein into the body.
At the same time that Jason McClellan was working on hexapro.
An organization called PATH was trying to figure out a
way to deliver more vaccines to poorer countries. Were extremely
(11:03):
interested in ensuring at countries where health budgets are not
strong have access to world class vaccines that are life saving,
on the proposition that everyone deserves to have access to
life saving vaccines. That's doctor Bruce Innes. He's a physician
and he's been working on vaccines for almost forty years,
(11:26):
tons of them against human papaloma virus, against rotavirus, gastroenteritis,
various cella vaccine, combination, measles, MOBSTERB varius cella vaccine, influenza viruses,
human papaloma virus. Bruce has been a PATH for five years.
The organization is based in Seattle and aims to improve
(11:48):
public health in lower income countries through innovation and partnerships.
At PATH, Bruce has worked on vaccines against RSV, meningitis, pneumonia, flu,
and now COVID. We realize that with COVID nineteen, even
early in the PATH demic, that no one would be
safe until everyone was safe, and that's why it was
(12:10):
important for us to think about in showing that all
countries would have access equitable access to covid vaccines. This
is where chickens come back into it. Remember an episode
three when we heard from the King of all vaccine inventors,
Maurice Hilliman. He grew up raising chickens on the family
farm and talked about how important they were to his
(12:32):
work in the lab years later and my career, chickens
were my best friend because I used them for so
many types of experimentation, and then we're breakthrough experiments. A
lot of vaccines are grown in chicken eggs, including lots
of the vaccines invented by Hilliman. Bruce and Path had
(12:53):
worked in the past with some middle income countries to
improve their capacity to produce egg based flu vaccines. An
egg based vaccine is literally one where the primary ingredient
the virus to be expressed, is grown and chicken eggs.
That's the most common way to make the flu vaccines
you get or can get every winter. They are really
inexpensive to make, and if you can make a covid
(13:15):
vaccine the same way, then you can theoretically just convert
a flu vaccine factory into a covid vaccine factory, and
we asked Mount Sinai. That is, they asked Peter Plais
and his colleagues at Mount Sinai if there was a
way to make a covid vaccine using a virus that
would replicate in eggs. They said, yes, We've done this
(13:36):
before with an avian virus called Newcastle disease virus virulent.
Newcastle disease or simply Newcastle disease, is an avian disease,
a bird flu. In other words, it can infect humans,
but rarely produce the symptoms in people. The disease is
caused by the appropriately named Newcastle disease virus, and it
(14:00):
spreads from bird to bird through their poop and other
bodily secretions. It's a big problem for commercial chicken factories
that squeeze a lot of chickens into densely packed spaces
amorally in my opinion, but that's neither here nor there.
Newcastle disease can spread on a factory farm and sicken
or kill their chickens. So the commercial chicken companies spray
(14:22):
Newcastle disease vaccines into their factories and vaccinate all the
chickens at once. Here's Peter to give a somewhat apocalyptic
visual in these big, big factories, and Newcastle disease virus
is put in canastus on the back of people and
they go into these factories. In spray life Newcastle disease virus,
(14:45):
chickens can also get flu viruses, and the factories didn't
want them getting that either. So Peter had worked on
a Newcastle disease vaccine that could also stop chickens from
getting the flu. Newcastle disease has also been explored as
a vector for carrying an ebola gene and for carrying
cancer killing viruses. And so we said, okay, why I
don't put the a saus coronavirus spike protein into Newcastle
(15:09):
disease burs And that's what we do at Mount Sinai.
Peter as colleagues, including Fluorine Cramer and Adolpho Garcia Sastre,
engineered a Newcastle disease virus that could carry hexapro into humans.
So the Newcastle disease is the vector for the hexapro
stabilized spike protein. They call the vaccine NDV HXPS NDV
(15:32):
Newcastle Disease Virus h XPS hexapro spike instead of using
super specialized machinery. They're making this vaccine and chicken eggs.
They've made multiple lots of vaccine, initially at pilot scale,
which might involve a few thousand eggs, and we're getting
typically about seven to eight finished vaccine doses per inoculated egg.
(15:55):
You can think of the egg as a mini bioreactor,
each one self contained bioreactor. And now they're in the
process of manufacturing investigational vaccine lots at full commercial scale.
Clinical trials and humans for NDVHXPS are already underway in Vietnam, Thailand,
and Brazil. In Vietnam and Thailand they moved on to
(16:16):
phase two after phase one trials show that the vaccines
are safe and produce an immune response in people. In Thailand,
they're also onto phase two and expect to produce twenty
million or more doses of the vaccine per year starting
in twenty twenty two. Brazil has entered phase one, and
if all three country trials proved successful, they can produce
(16:36):
vaccines fairly quickly since they already have functioning flu vaccine
production facilities. I can't tell you our quick clin Nicola
and animal challenge experience, how compelling. I can't take I
can't protect every mouse and every hamstand the world against
any sauces. It works beautifully in the animal systems we had.
(16:57):
Based on the animal studies, you can feel like it's
a really very good sign, no doubt, no doubt. So
Pete is very confident that the Hexa pro Newcastle hybrid
vaccine will work well in people, and let's hope that
it does. Not only is it really cheap and easy
to produce, there's another benefit to this vaccine. One of
(17:18):
the reasons if fives are in well, the end of
vaccine also expensive. You know what. One of the reasons
is stability. They have to have the binus foody and
minus eighty degree freezers explorinly expensive. All of vaccine is
stable at kitchen refrigeration temperatures two to four degrees four weeks,
so it is very very stable. That's one of the
(17:41):
biggest issues with modern medicine in developing countries. It's not
always possible to keep it cold enough. Ndv HXPS helps
with that a ton by staying stable at refrigerator temperatures,
and the manufacturers that Path is working with can make
a lot of vaccine in big bunches. Here's Bruce. A
(18:02):
typical lot size involves more than five thousand eggs that
are inuculated and harvested three days later. And when I
say innoculated and harvested, you put a small amount of
seed virus into the egg. It propagates in the embryo
when it's incubated at thirty seven degrees. Then the eggs
are chilled overnight at the end of a seventy two
(18:23):
hour period and the egg fluids the whites of the
egg are harvested and from that you can purify the
virus inactivate it formulated for administration. So the Southeast Asian
countries will have a typical lot size of around fifty
to forty to fifty thousand eggs per lot, and each
(18:44):
manufacturer can initiate multiple lots in a given week. Vietnam,
for example, as of this recording, is still instituting a
severe nationwide lockdown because only seven percent of their population
has been able to get fully vaccinated, so being able
to produce their own vaccine would be huge. Is a
(19:05):
middle income country, relatively wealthy by world standards. Seven percent
is high compared to low income countries, which, like I said, earlier,
are only two percent vaccinated. Right now, the US and
other wealthy countries maybe doing okay with vaccination, but we're
doing a shit job as a planet. The Newcastle hexapro
(19:27):
vaccine could help change that. Our aspiration, and we shared
this with the manufacturers, is that this would be one
of the most affordable vaccines possible. The starting material is
an embryonated egg, a fertile egg and a small bit
of seed virus, and the cost of eggs for production
(19:48):
for vaccines is somewhere between twenty five and thirty cents
an egg. And I told you that there's seven to
ten doses per egg, so that's only pennies per dose.
Of course it has to be mixed with a bunch
of other ingredients first, but you can imagine the NDVHXPS
vaccine ends up pretty cheap. If the main thing doing
the work in it only costs a few cents, that's
(20:09):
a good way to get the world vaccinated. This is
a grand experiment. The inactivated Newcastle disease virus vaccine has
never been administered to human subjects before. It's brand new technology.
It's very very exciting, and the preclinical data were astonishing.
We think that the covid pandemic won't abate until everyone
(20:32):
has access to vaccine. There are many countries that have
been left behind. We hope that the ndv hxp S
vaccine will have an important impact on helping to abate
the epidemic and will be used in years to come
for controlling endemic covid disease which is likely to continue
(20:53):
to circulate them on human populations. The next and last
episode of long Shot is going to be a little
different than the others. We're going to go over everything
we've talked about in a series and put it all
together into one story and then fill in some gaps
from the history of vaccines that's next week on long Shot.
(21:17):
Long Shot is a production of School of Humans and iHeartRadio.
Today's episode was produced, written, and narrated by me Sean Revive.
A co producer is Gabby Watts. Special thanks to Noel
Brown and iHeartRadio. Executive producers are Virginia Prescott, Elsie Crowley,
and Brandon Barr. Fact Checking for this episode is by
(21:38):
Adam Shadow. Long Shot was scored by Jason Shannon. The
score was mixed by Vic Stafford. Sound Design and audio
mixed was by Harper Harris with Tunewielders School of Humans
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