Welcome to LSU, HTM viral season 3, a podcast, exploring the science behind Global and public health.

I'm Carl burn, I'm Amy Thomas, I'm Naomi Stewart.

And every Fortnight will explore the latest developments in the covid-19 pandemic and take a deep dive into vaccines and vaccinations.

The latest figures show that the our number in the UK has dropped to between not point eight and one meaning that Transmissions of covid-19 are no longer Rising exponentially, elitist seven-day average.

For the UK is just over three cases per 100,000 people with the lowest rates in wheels and the highest in Northern Ireland, this has led the UK to lower its covert alert level from 4 to 3 as the current lockdown is set to.

He's further, including people being allowed to cautiously hug in England.

The UK has not given over 50 million doses of the vaccine 35 million people about two-thirds of adults, have received their first dose and of those over 16 million have also received their second in the USA, more than two hundred and fifty, two million vaccine doses have been given with just over two million doses a day, being administered over the last week.

More than 1.2 3 billion doses.

Have now been administered across 174 countries leaders vaccination rate was roughly.

Nineteen point four million doses a day.

The increase in vaccination rates is something to celebrate the first 100 million.

Doses, took two months to deliver on the most recent hundred million doses.

Took only five days.

However, these huge achievements are not being seen globally.

World Health organization's director-general.

Ted was Adam Graces.

In his opening remarks at the one shared world event earlier this month, shared this Stark fact more than 80% of vaccines administered have been in high and upper middle income countries while just not point three percent have been administered in low-income countries.

He also stated that vaccine nationalism will only prolong the pandemic, the economic turmoil, it causes the restrictions on travel and trade and increase the chances of variance emerging that avoid vaccines.

The Kovacs of vaccine sharing program was designed to share the risks of vaccine development and offer a mechanism for pooled procurement and Equitable rule out around the globe.

But many of the same wealthy countries that expressed support for Kovacs were in parallel pre-ordering.

The CM vaccines on which Kovacs was relying.

This is one of the reasons why the wealthier countries are able to offer so many vaccines.

While the poor countries are not being able to last week, the by did ministration made the surprise announcement that the US would support.

Proposal to, we have patents on covid-19 vaccines in response to the pressing need for more Global Supply while this is a step in the right direction, the EU hasn't followed suit yet and it will be likely 2022.

Before this really has any effect in other vaccine, use under 40s in the UK are to be offered alternatives to the AstraZeneca vaccine, the UK's medicine.

Safety Regulators said that there had been 242 clotting cases and forty nine deaths with twenty-eight point five million doses of the vaccine being administered but Risk is slightly higher in younger age groups, low levels of coronavirus cases and the availability of alternative.

Vaccines have also informed.

This decision Professor, we Shin Lem from The Joint Committee on vaccination and immunization.

The jcv I said, they were putting a high priority and safety and he expected the move would serve to boost confidence in the vaccination program.

To put this into perspective, immunization is estimated to have already saved, 10,000 lives in the UK.

And finally how an online game saved scientists, 330 years of research time and covid-19, Eve online is a massively multiplayer online game.

Where citizens can build, Starships mine, asteroids, join factions and go to war and now through a citizen science project called project Discovery, players are able to help scientists in the real world solve problems that need human input.

Previously project Discovery had carried out Research into protein folding and discovering planets orbiting other stars but over the past year over 300,000 Eve online players have completed, one point four Million analysis tasks which of see if scientists over three hundred and thirty years.

Worth of research into how the immune system responds to covid-19.

This has been achieved by getting players to play a minigame inside the me in Eve online where they can win.

Rewards for completing tasks, they main tasks involved in this Is that players simply point and click to create ships around a massive clusters.

These clusters represent sales of red, green, blue, and yellow, and by identifying various colors and various ships.

They're able to detect High proteins on the cell surface are reacting to covid-19.

I think this is a fantastic use of Citizen science and real world.

Example of high public engagement can help scientists solve problems, In this series so far, we've looked at the history of vaccines, what goes into a vaccine and how they're tested in licensed.

But today I'm going to take you on a journey through the actual manufacturing process of the world's newest kind of vaccine those based on mRNA Pfizer bio ntek vaccine was the first mRNA vaccine to be authorized for emergency use in people and the manufacturer, every single dose starts in a large glass building, not far from the shores of the Missouri River.

This is the home of one of Pfizer's R&D facilities in Chesterfield, a town in the western suburbs of st.

Louis in this Laboratories are growing.

The bacteria that contain the gene for the covid-19.

Spike protein.

Essential to the MRNA vaccine, the start of a process that will take two months and see the components travel to numerous different states.

And in the case, where vaccines destined for outside of the USA will travel across the Atlantic to two different European countries.

Back in the early parts of 2020 scientists, created a piece of DNA that coded for the covid-19 spike protein.

It inserted this into a circular ring of DNA called a plasmid plasmas occur naturally in bacteria and are very useful for researchers who want to clone short sequences of DNA.

These plasmids are stored.

Incredibly low temperatures - 150 degrees Celsius or - 238 Fahrenheit and make up the master cell Bank from which all the vaccines will.

Eventually be created the first step in creating a batch of vaccines involves a robotic arm, locating and retrieving a box.

Containing this master cell Bank, from inside a large, cryogenic storage tank.

A technician, then removes one of these vials, each about the size of your little finger to go on to create up to 50 million doses of the vaccine.

Vaccine obviously a vile this small contains nowhere near enough material and this is where the next step begins, scientist carefully thought the plasmids and modify a batch of E coli bacteria in order to allow them to take up the plasmids inside their cells.

These modified, E.coli are.

Then mixed with a growth medium which is a sterile warm environment, containing all the nutrients necessary for bacteria to begin multiplication.

The bacteria are left overnight in this flask and the next day are transferred to a large fermentation tank cleaning a warm nutrient broth.

After a Time, the E.coli will start to feed in the rich broth and divided over the next four days.

The bacteria will feed divide feed and divide up to every 20 minutes until there are trillions and trillions of the covid-19 plasmid.

Now, a trillion is a very large number.

If you were to count to 1 million, it would take you about 11 and a half days.

If you were to count to 1 billion, it would take you about 30 one point seven years, but the count 21 trillion and that would take you.

Thirty One Thousand, seven hundred years counting one number, every second, these are vast numbers of bacteria.

Vast numbers of plasmids.

At the minute.

These plasmids are still inside the E.coli.

So scientists have to break open the E.coli cells to release the plasmids.

They do this by adding a strong Alkali to the soup, which causes the bacteria to burst open.

Then in order to purify it, I add some acid and SDS which is the same substance that makes toothpaste foam and this causes the bacterial DNA to come out of solution.

Meanwhile, the plasmids containing the covid-19 Genes remain in solution at this point.

The liquid is filtered removing all of the bits of bacteria and leaving only the plasmids at this point, scientist performed.

The first of many tests confirming the quality and purity of the plasmids.

Comparing the DNA sequence against previous samples to make sure that there's been no change in the DNA sequence and that no mutations of occurred If the batch passes, these tests enzymes are added to the mix.

These enzymes work, like, biological scissors and cut the covid-19 sequence.

At either end, leading to A straight piece of DNA in a process called linearization, which takes about two days to accomplish.

Not any remaining bits of bacteria or plasmid, or filtered out leaving the purified, DNA.

The DNA sequences are tested again and stored in one liter bottles, each bottle will go on to produce up to 1.5.

Five million doses of the vaccine.

At this stage, the DNA is ready for its first trip to another Factory.

Each bottle of DNA is frozen bagged and sealed.

And a temperature monitor is included to make sure that it remains at a viable temperature throughout its trip up to 48 of these bottles are packed in a container with enough.

Dry ice to keep them Frozen at around, minus 20 degrees Celsius, or but -4 degrees Fahrenheit.

The containers of then locked to prevent any tampering and shipped to the factories where they'll process the DNA into messenger RNA, the active ingredient of the vaccine.

some of these will end up in Andover Massachusetts for use in the continental United States While others will be flown to mines in Germany to the Bayonne Tech facilities there Inside these factories, the messenger RNA Suites are clearly marked.

This is for the protection of the RNA.

The environment is full of enzymes called are any Aces, which unlike the previous enzymes, which worked like biological scissors, these work like biological shredders, they seek out and Destroy any RNA.

They come across are in is is defined in all cell types and organisms from bacteria to bananas to people exist on your skin and only a very Very small amount is needed to destroy an RNA sample.

This means it's very important to make sure that there's no rnases in the environment.

Inside the MRNA sweets, when it's time to start, creating the RNA, five bottles of the purified, DNA are defrosted, and mix with the building blocks of mRNA then, over several hours.

Enzymes will uncoil, the pieces of DNA and transcribe them into strands of messenger RNA.

After the transcribing is done, the mixtures moved to a holding tank Which again filtered to remove any of The Unwanted DNA, enzymes and other impurities.

Each batch of purified RNA is repeatedly tested to make sure that it doesn't differ from the original genetic code.

And after scientists confirm that it's pure and that its genetic sequences correct.

It's divided into ten sixteen L bogs of raw materials.

At this point, each bag is frozen packed in dry, ice once again and shipped to another Factory in the USA.

This Factory is in Ooh, Michigan, while in Europe, the factory is in pores in Belgium, samples are also sent back to the Chesterfield facility to double-check in match.

The original sequence has the Michigan and Belgian facilities, keep the bags of RNA Frozen until needed and then follow enough to produce 3.6 million doses of the vaccine or what, 600,000 vials cathode mRNA is mixed with water in preparation for making the final vaccine as has been previously.

Mentioned mRNA is easily destroyed By various enzymes in the environment in order to protect the MRNA and help it to enter human sales.

It's coated in oily molecules called lipids each strand.

Of messenger RNA is coated in a multiple layer of lipids.

Through a precisely controlled process involving 16 pumps that carefully control the flow of the MRNA mixture and lipids mixed with ethanol as the lipids come into contact, with a naked strand of mRNA.

They snap around it in a billionth of a second, forming a nanoparticle.

While there are numerous challenges involved in synchronizing, it pairs of pumps, Pfizer decided to use an existing technology rather than build a larger unproven method.

The vaccine is then filtered to remove the ethanol, concentrated and filtered again to remove any final impurities, S10 sterilized, and ready for bottling computers.

Watch over hundreds of thousands of small sterilized glass vials.

With an array of cameras, taking hundreds of shots of each vial to ensure that there are no imperfections.

Each file is also Back to, to the vacuum to ensure that there are no leaks.

The tested vials, their narrow, to a single lien or machines, inject enough concentrated solution for six vaccinations into each vial.

The vials were sealed with foil and capped with purple Lids at a pH of around, five hundred and seventy five vials per minute.

It's a Race Against Time from defrosting to bottling as the MRNA will degrade, if it's left on Frozen for too long.

The filled vials are inspected again.

Then quickly patched up and placed in giant industrial freezers where over a couple of days, their temperature will drop to the minus 70 degrees Celsius needed for long-term stable storage.

They remain in the freezer for four weeks with additional testing being done samples, are sent back to the facility that produced the MRNA and also to the Chesterfield site that provided the original DNA templates, 60 days after the plasmids were defrosted and Chesterfield average over half of those days.

Goes on testing.

The vaccine is finally ready to ship.

Five trays of vaccine.

Each containing 195.

Vials are placed in an insulated box with GPS, trackers and temperature, sensors along with 20 kg of dry ice are sealed and sent to the vaccination Center where they will soon begin their mission of training, your immune system to recognize covid-19, and help the world find its way out of this pandemic.

I hope you enjoyed that Journey from the lab to the jab.

It was adapted from an article by Emma cot, Elliot, de Bruin, and Jonathan Quorum published in the New York Times in the 20th of April coming up in the second half of this season.

I mean I owe me and I will be joined by more experts from LS HTM Beyond as we look at vaccine manufacturer and we'll light address vaccine.

Latency and take a closer look at statistical risk and how to make sense of it, as well as vaccine surveillance, and the need for continued monitoring for new variants.

It's going to be necessary to keep us safe as time goes on.

And in the meantime, if you'd like to get in touch with comments about previous episodes or questions you like to see us answer in future episodes you can email us at comms @l s HT m dot ac.uk that's Comm s at lse HT m dot ac.uk and if you haven't already be sure.

Sure to subscribe to this podcast.

Leave us a review and share it with your friends, family and colleagues.

Until next time, I've been called burn and you've been listening to L sh T m-- viral.