- 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.