Studying Coronaviruses: Vectors to Vaccines

https://www.ibiology.org/human-disease/coronaviruses

Infectious disease researchers Dr. Tracey Goldstein and Dr. Koen Van Rompay discuss the process of detecting and identifying a new coronavirus, and the steps needed to develop a vaccine.

When an infectious disease outbreak happens, medical workers and public health officials mobilize, but there are also teams of researchers that snap into action. Dr. Tracey Goldstein and Dr. Koen Van Rompay are both actively involved in different initiatives to find answers surrounding the COVID-19 pandemic. They talk about the process of studying coronaviruses and other infectious diseases, the steps taken once an outbreak hits, and the ways in which this process could change for the better. The changing world we live in makes predicting outbreaks a challenge, but each one teaches us something new about how to understand and to respond to the next.

To find out more about our conversations with Dr. Goldstein and Dr. Van Rompay, you can read their extended interviews here:
Continuing the Conversation:  Dr. Tracey Goldstein on One Health, Bats, and Looking Ahead
https://www.ibiology.org/continuing-conversation-tracey-goldstein
Continuing the Conversation: Dr. Koen Van Rompay on Vaccine Development and Animal Models
https://www.ibiology.org/continuing-conversation-koen-van-rompay

Speaker Biographies:
Tracey Goldstein, PhD
Tracey Goldstein is a Professor in the Department of Pathology, Immunology and Microbiology and Associate Director of the One Health Institute. Dr. Goldstein is Co-Principal Investigator and Pathogen Detection lead for PREDICT, a project of the USAID Emerging Pandemic Threats program. She oversees the One Health Institute Laboratory and the Marine Ecosystem Health Diagnostic and Surveillance Laboratory. Dr. Goldstein earned her B.S in Aquatic Biology at UC Santa Barbara and her PhD in Comparative Pathology at UC Davis.

Koen Van Rompay, DVM, PhD
Koen Van Rompay is a veterinary researcher from Belgium, who completed his PhD at UC Davis. He is a Core Scientist in the Infectious Disease Unit at the California National Primate Research Center (CNPRC) at UC Davis. Dr. Van Rompay’s expertise is in nonhuman primate models of viral infections, most notably HIV and Zika virus, but more recently also COVID-19. His research has a special focus on vaccines and antiviral drugs to prevent or treat infection with these viruses. He is also the founder of the nonprofit organization Sahaya International.

Credits:
In addition to iBiology staff, this video was made possible with:
•Editing by Isabel Ponte and Adam Bolt, The Edit Center
•Design and Graphics by Chris George and Maggie Hubbard
•Videography by Jeremy Poulos, UC Davis Academic Technology Services
•Images and Footage from NSF, NIH, UC Davis School of Veterinary Medicine, California National Primate Research Center, Nigel Walker
•Music from APM Music (“Idea Space”), Jingle Punks (“Needle Drop”), and iSpy Music

>> My name is Tracey Goldstein,

I work at UC Davis School
of Veterinary Medicine.

I'm a Professor in the
Department of Pathology,

Microbiology, and Immunology,

and Associate Director of

the One Health Institute.

And what I do is really studying
diseases in animals

trying to understand how they may
spill over from animals into people.

A good example is this
coronavirus outbreak right now,

where it's affecting people,

but we understand that the virus
likely came from animals.

My name is Koen Van Rompay.

I work at the

California National Primate
Research Center at UC Davis

What we're trying to do is create

the most effective vaccines.

And trying to develop antiviral drugs

to treat people who are already infected.

When there is a new viral disease,

the first thing is you have to know

what virus it is.

You want to know who your real enemy is.

In the old days, methods were very slow --

techniques like electron microscopy.

These days, with sequencing
the viral genome,

in a few days you can usually find out

what kind of virus is causing
a new epidemic.

So, when you sequence the genome,

you can start to look at where there

might have been a mutation,

and that will tell you what parts
of the viral genome

are important, for example,

to enter human cells.

In many of these animal viruses,

they're able to infect animal cells,

but they don't have the same

machinery to infect a human cell.

But RNA viruses, like ebolaviruses
or coronaviruses,

their genomes are a little bit
more unstable

They're sort of always changing.

These big changes in the genome,

are probably happening all the time,

and sometimes they're random,

but every once in a while,

a change might occur
in a part of that genome

that allows it to suddenly become,

you know, infectious in a human.

To develop a vaccine against
a new infectious agent,

we can really learn a lot
from the natural biology

of the virus.

In order for a virus
to infect a human cell,

it needs to be able to bind

to what we call the receptor

So, it's sort of like a lock and key.

When you think about coronaviruses,

the spike protein, which is

the proteins on the
outside of the virus...

we know that that's
important for the virus

to be able to enter the human cell.

Once you know that,

you want to see,

which part of the virus should I use

in the vaccine construct?

What we try to do with the vaccine

is to come up with a strategy

that mimics a natural immune response

to infection.

It can either be by using

a live attenuated version of the virus

or taking some part
of one of the proteins.

We really want to have something

that's specific against the virus,

but then has minimal cross-reactivity

to normal host proteins,

to minimize the chance
for any side effects.

In 2016, when Zika virus broke out,

different primate centers...

we started working groups.

Something similar is now also starting

for the new coronavirus.

People have been really forthcoming

with new information

as it's becoming available,

sharing it even before
it's being published.

We are going to have meetings

to really share our progress

and brainstorm experimental designs.

Soon, one of the first centers
is actually going

to infect some monkeys with coronavirus.

We want to study diseases in animal models

that mimic the human disease.

We move this up from mice and rats

to higher species.

The species that's closest to humans

are actually non-human primates

such as rhesus macaques.

And they are usually the final step

for moving something
into human clinical trials.

Human trials are done in different stages.

Phase 1 trial is to see, is it safe?

If that looks promising,
then you go to Phase 2,

where you test it in more people.

And the Phase 3 trial is the first one

where you really want to look at,

does the vaccine work?

Does it protect against infection?

If we can all communicate

and we can collaborate very rapidly

-- we can share protocols --

that's how we can make progress
a lot faster.

I think during an outbreak,

it's very much a day-to-day response,

trying to understand
how to get ahead of the curve

and control the problem.

But after that is when, really,

the big work begins.

Many of these diseases
that cause pandemics

come from wildlife.

And our world is changing

really, really quickly.

We're moving into places where
we didn't used to go with our animals

Cutting down forests
to make space for farms

or going into caves for mining.

Our behavior is what's facilitating,
likely, the spillover

What we've been doing is
sampling in all of these places

around the world.

We focus on bats, rodents, and primates.

So, what we wanted to do was

specifically look and see
how many different

coronaviruses we could find
in the different species.

And what was really interesting is,

despite us sampling all
of these different taxa,

about 98% of the
coronaviruses that we found

were in bats.

And then we mapped
the diversity of the bat species

that we found those coronaviruses in.

So, sort of a hotspot map.

It's got the dots of
where the viruses are,

and then colors of where we found

high diversity of
the different bat species.

And that is useful
because it can help us to

project where we might find
other coronaviruses,

if we know where those bat species are.

The investment that we put
in infectious disease research

pays off --

more than just that one
particular disease you study,

but really by improving
the overall knowledge

of infectious diseases
of the immune system.

What there needs to be is

sustained research support

for these things before, during,

and after outbreaks.

The outbreak's over, and then,
the funding goes away,

and then vaccines sit in labs

not being completed and not being trialed.

I think we need to figure out a way
to not do that,

not have this boom and bust,

but be always
supporting that type of work.

If you could sequence the genomes

of, say, a bunch
of different coronaviruses,

how many different
cell types can they infect?

And then, what would you
have to do to change them?

You could potentially, over time,

generate data that would start

to maybe show you some things

that you could predict.

We can use that existing knowledge,
that database,

to really come up with interventions

a lot faster to attack that new disease.

If we can understand
more about the viruses

that are out there,

and have therapeutics and vaccines

and other things in place,

we can be better prepared to respond

to the next thing

versus scrambling every time

that something new pops up.