Frankenvirus

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 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. 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 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 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

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 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 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 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 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 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 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 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 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 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 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

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 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 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 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 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 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 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

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. 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 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. 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

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 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 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, 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 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 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 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 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 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 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 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 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, 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 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 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. 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 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 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. 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 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

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 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 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

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 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 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 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 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 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 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. 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 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