3 Researchers Break Down COVID-19 Vaccines They’re Developing (3 Types) | Cause + Control | WIRED

published on July 2, 2020

– I called up three vaccine researchers working

on three different types of vaccines

Thank you so much for joining us,

especially given how busy you must be right now

– All right

– So, the traditional way that vaccines have been made

is to inject either a weakend or dead version

of the virus into the body so that the immune system

is prepared to fight the real thing

But, many of the COVID-19 vaccines currently

in development are using new technology

– Hello, my name is Doctor Peter Hotez,

and our team was developing a recombinant protein vaccine

– My name is Joseph Kim

Inovio is working on a DNA based vaccine for COVID-19

– My name is Katherin Jabsen, and we are working on

mRNA vaccine candidates to protect against COVID-19

[solemn music]

– There are over 30 companies working

on different types of vaccines,

and these three researchers are all

at different stages of the timeline

– We're now in the process of preparing our application

to get the green light to begin clinical trials,

– Inovio is currently conducting

a phase one studies for its vaccine

– We are currently in a phase one two trial

in the United States and in Germany

evaluating four vaccine candidates

– Coronaviruses are RNA viruses,

but your vaccine is a DNA vaccine, so how does that work?

– Inovio's DNA vaccines work by injecting snippets

of DNA as a vaccine into the person's skin cells

The DNA, once delivered, instruct the cells

to manufacture the antigens encoded by the DNA

And then, once these antigens are produced in the body,

the immune system of the person

reacts to it by generating strong immune

responses against those antigens

– An antigen is a molecule that's foreign to your body

and can elicit an immune response

DNA and RNA vaccines, instead of giving you the virus,

they're giving you some genetic code that your own cells

can use to make a small piece of the virus

That's what your immune system is exposed to,

and that's what it knows how to fight

– The beauty of this is a safe way to teach

the immune system what the real intruder would look like

So, mRNA is coding to make proteins

Our cells are loaded up with mRNAs

that are coding for many different proteins

that are required in a human cell to do

what the cell needs to do

– DNA codes for RNA, RNA contains the instructions

to make proteins, and proteins are the basic building blocks

for many parts of our body

– So, we taking advantage of this,

of making a specific mRNA that now is not coding

for cellular protein, but it's actually coding

for a viral protein

– Compare this to a protein based vaccine

– A recombinant protein vaccine contains pieces

of the pathogen that we're hoping to protect against

– Can you define the recombinant protein vaccine

that your team's working on?

– You're basically immunizing with a piece of the virus,

and that piece is genetically engineered into yeast

The way our vaccine works is we formulate it

with something called alum to make it more immunogenic,

and then you inject it, and it elicits an immune response

consisting of antibody and also T cells

– How is a protein vaccine different

to an RNA or a DNA vaccine?

– Well, a protein together with the aluminum,

what's called adjuvant,

has the ability to directly

stimulate the production of antibodies

That's in contrast to an RNA or DNA vaccine

whereby the RNA or DNA has to be taken up by a cell

And then, one of your own host cells

has to manufacture parts of the protein,

and then presented to the immune response

So it's two or three degrees of separation away

from directly presenting to the immune system

The advantages of our vaccine,

it says that old established technology

that we know can make a vaccine

RNA and DNA vaccines, they've never led

to the licensure of a vaccine before

The advantage of the RNA and DNA approach

is you can make them pretty quickly

and accelerate the timeframe

– Most COVID-19 vaccine development started back

in early January when Chinese scientists

first shared the genetic sequence for this new virus

with scientists around the world

– We were working on a seasonal influenza vaccine

based on mRNA when the pandemic

came upon us fast and furiously

when the Chinese made the sequence available

of SARS CoV-2, our partners at BioNTechs,

they took the sequence and immediately started

to make COVID-19 specific mRNA constructs

– we were able to design a vaccine sequence

in three hours by applying the known DNA sequence

of the virus, which was available from China,

leveraging what we know of the coronaviruses,

and what targets are appropriate as a vaccine targets

We were able to hone in and extract out the DNA sequence

for the spike protein, and then turn that sequence

into a very well optimized vaccine sequence

– Both of these nucleic acid vaccine companies

built their vaccines from scratch

once they downloaded the genetic sequence

for this new virus

Doctor Hotez's team had a different reaction

when they saw the genetic sequence

– I'll never forget it

When they put their data up on bioRxiv,

and I downloaded and said, "Holy crap

"We may have a vaccine that could cross protect"

We've been working on coronavirus vaccines

since 2011 for nine years

– The team at Baylor College realized

that they might have a vaccine in their freezer

that would work against this new coronavirus

– Maria Elena, my science co-partner,

had the vision to keep it on stability protocol

Meaning that in case people did get interested in it,

when you put a vaccine on stability,

it's taken out of the freezer every six months

and confirmed that it hasn't been corrupted or degraded

What we had was, we had the genetic code of the virus

Most importantly, since we were focused on a component

of that spike protein called the receptor binding domain,

you know, if you look at a picture of COVID-19,

it looks like a donut with a piece of RNA stuffed inside,

and then emanating out of the dome are all those spikes,

and the rounded end of those spikes

is the receptor binding domain that docks with the receptor

We saw that there was quite a bit of similarity

It was not a perfect match,

but close enough that we thought

that our vaccine could cross protect

– Vaccine research begins

with preclinical trials on animals

What animals have you been testing your vaccine in?

– We've been testing our vaccines in two types of mice

One is a genetically modified mice

that makes the human ACE2 receptor

The other mice that are infected with moss adapted virus

– Vaccine candidates starts in mice,

'cause they are very easy to deal with

– Mice are easy to come by

You can test many, many different constructs in a mouse

It's a pre-screen

And so, a lot of constructs went into mice

Four came up on top, they gave good responses

T cell responses expect a T cell humoral B-cell responses

to make antibody and DNA responses

– Typically, preclinical trials take years,

as we heard from Doctor Hotez

But right now, these companies are getting through

preclinical trials remarkably fast

And how is it that you were able to start

preclinical development on day one?

– We just did it faster and in parallel

We started the mouse testing same time as the Guinea pigs,

almost the same time as the rabbits,

almost the same time as the nonhuman primates

These are usually done in a serial steps

We just did everything in parallel

– Everything happens in parallel,

but we are in a very unique situation right now

in such an emergency

The question was, can we make a decision

in a mouse across those four constructs?

And the answer was no, because mice ain't men,

so we have to learn what would give us

the most potent vaccine construct

Actually, we made the decision

to move this into clinical studies

– This is often being pitched as a race between vaccines,

and I don't see it that way

I think you're gonna probably see multiple vaccines emerge

– Once researchers are satisfied with the immune response

that they're seeing in preclinical testing,

then they move on to human testing

[intense music]

How far into clinical trials are you,

and what's that process been like?

– We just started a phase one trial beginning of April

with the first volunteer being dosed

All 40 volunteers received their first dose

– We have developed a phase one two program

that is really also a unicorn

Very unique, because it is what we call a seamless trial

It starts with a small group of individuals

that will receive the four candidates

We then will make very quick, real life decisions based

on the emerging data of which candidates will move ahead,

and which candidates will be eliminated

– Pfizer is doing phases one and two

of its clinical trials at the same time

Many companies are doing a lot more in parallel

than would normally happen

What all of these vaccine scientists are looking for

is the right kind of immune response

What kind of immune response did you see with your vaccine?

– We were able to see very strong,

robust antibody and T cell immune responses

against our vaccine antigen

– The immune response that our vaccine

is inducing is actually able

to prevent the infection or at least the disease

in the animals that is to induce a response

that we call an innate immune response

So, that's usually immune response

that recognizes dangerous signals,

like there's a virus coming in,

or there's a bacterium coming in

While this is happening, the RNA is also inducing

what we call adaptive immune responses

So, here we get T cell responses,

both T cells that give help to other parts

of the immune system, but also T cells that by themselves

can recognize virally infected cells

and kill those cells to eradicate the infection

So, that was also very important

This is what we call the humoral part

of the immune responses so that's immune response

that produces protective antibodies

We like the RNA, because all three arms

of the immune system are triggered at the same time

– Can you walk me through how your vaccine

would work in somebody's body?

– The immune system sees these genetically

engineered antigens and produces an antibody,

and the antibody binds to the spike protein of the virus,

then shuts the virus down

– Once a vaccine makes it through testing,

the next major challenge is storage,

and the stability of a vaccine can make it or break it

How does a protein vaccine compared

to RNA/DNA vaccines in terms of stability,

and what temperature you have to keep at?

– DNA vaccines, another advantage is,

you don't need to keep it cold

Our vaccine, you need to keep cold

– DNA plasmids is one of the most stable

biological molecules in the world

We've demonstrated our longterm storage

is at normal refrigeration temperature

We can make it set down in room temperature

for over a year with perfect stability

– Our vaccine candidates right now are stored frozen

The stability of RNA, there's still some work to do

In order to get the RNA into the cell,

it needs to be formulated for lack of a better description,

in a little fat droplet

So, there are lipids involved

They surround the RNA, they help stabilize the RNA,

and so this little fat droplet then serves as a vehicle

to be taken up by a human cell

– Once the vaccine's made it through clinical trials

and safety testing, the next big step

is scaling up and manufacturing

– I think the way the approach nationally

has been to try to get lots of vaccines

accelerated into clinical trials

So, you get lots of shots on goal,

and then you have this interesting phenomenon

of manufacturing at risk

That's the term Doctor Fauci uses,

which is manufacturing these vaccines in scale,

even though you don't know it's gonna work or if it's safe

– We've been thinking about scaling up our manufacturing

of these vaccines from day one

You know, if we're successful with COVID-19 vaccine,

we need to manufacture billion doses a year, right?

Potentially, at least hundreds of millions of doses a year

So, that's a scale that we were not

previously built to handle

Thankfully, there are a lot of folks

who have committed both from the government levels

and the NGO levels to support the scale up

– We have this, of course in mind,

and already working on the scale up activities

to at least produce hundreds of millions of doses

– The question on everyone's mind,

when will we have a vaccine?

– If everything goes well, and if the emergency use path

is available,, potentially by the end of this year

– I don't see a path by which you're going

to have a vaccine available by the fall

I don't see how it's possible to collect sufficient data

to show one, the vaccine works,

and second that the vaccine is safe

– In our situation, we don't have years,

we don't have months, time is up

We need to be really, really fast

What took years we now do in months

In my wildest dreams,

I would have never even imagined that this is possible

– This accelerated timeline for development

of a COVID-19 vaccine is unprecedented

We have never seen vaccine development happen

at this rate with so many different candidates

all being tested to fight the same virus

We're seeing cutting edge,

never before approved technologies being tried

and tested alongside much more traditional methods

There are so many different kinds

of vaccines being developed right now,

so I hope this brings some clarity

about the different methods that are being used

Check out my other video,

which explains just how soon we might have a vaccine

Thank you so much for taking time out

of your busy schedule to talk with me

– Thank you very much

It was a pleasure talking to y'all

– No problem at all

– All the best, bye bye

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