There are no guarantees in science

i knew from when i was in high school

that i wanted to make a difference in

this world

for me a career in science seemed like

the best way to address

some of the problems that the world is

facing this year i had a shot at that

life goal

i am one of the co-lead investigators in

uq’s program to create a covert vaccine

i’m also one of the inventors of the

underlying technology that looked like

it would make this a reality

we were close but it didn’t quite play

out the way we had hoped

right now there are tens of millions of

doses of our vaccine

we’ve shown that it’s safe and then it

can generate an immune response

that’s likely to be just as protective

as any of the other candidates being

progressed

and are sitting in freezes likely to

never be used

it’s just a tad soul destroying but a

vaccine needs to be perfect in every way

the vaccine we produce is what is called

a subunit vaccine

for this we just produce a part of the

virus and not the whole thing

for covert we just make the spike

protein that sticks out from the surface

of the virus

but it’s held in the right shape so that

it exactly

matches the shape that is present on the

virus the spike is held together by what

we call the molecular clamp

you can think of the molecular clamp

like a bulldog clip holding the protein

together so

it’s in the exact same shape as was

present on the virus surface

we give this as a vaccine to teach the

body’s immune system

what to be on the lookout for so it’s

important that the shapes exactly match

the issue with our vaccine is that the

molecular clamp technology

is based on a small fragment of one of

the hiv proteins

we chose this fragment because it is

well understood

and a highly stable structure it is so

stable in fact

you would have to heat this bulldog clip

up to about 90 degrees before it would

open and drop its papers

we knew that people who received this

vaccine would likely generate a response

to the sequence within the molecular

clamp we also knew that it was a

possibility

that this response could be

cross-reactive to some of the hiv

diagnostics

all participants were advised that there

was a possibility of falsely testing

positive

for hiv however we didn’t think that was

likely

however science is hard and that’s

exactly what happened it

in no way diminished the immune response

that would be protective against

covert but if the vaccine was used in a

population wide scale

it would create problems for hiv

diagnosis

it’s disappointing and frustrating yes

but in science this isn’t unusual

this type of thing happens every day

just not usually in the middle of a

global pandemic and vaccine race

when the eyes of the whole world are

upon you

the fact that this vaccine will not

progress does not diminish all of the

work that went in

by many of people to its development

and so to honor the work that everyone

has contributed

i’d like to highlight exactly what goes

into a vaccine

to do that we need to go back in time

all the way to 2011.

at the time i was thinking about the

need for something like a clamp to stop

the proteins i was working on from

falling apart

that was when the idea came to me to use

the highly stable structure

within gp41 from hiv as a clamp to hold

these proteins into the correct shape

and then use them as a vaccine as is the

first step with

any a great idea i discuss this with my

best mate over a few beers at the pub

dan watterson is not only my best mate

but is

a work colleague and the most passionate

and intelligent scientists that i know

dan and i usually enjoy discussing some

crazy and out there ideas

however we both knew that this was

legitimately a good idea

and we could both see the potential

we then pitched it to our boss paul

young

who has always been a supportive and

great mentor

and paul gave us the go-ahead to work on

this as a side project

it was around a year before we got the

first results showing that this

technology could work

this is with the virus called

respiratory sensitive virus

it is a common cause of bronchiolitis in

young children

within another five years of working on

this as a side hustle

before we receive the first funding for

this what to support this

work over that time we had shown that

the

technology worked for eight different

viruses including

ebola influenza and middle east

respiratory coronavirus

over that time i wrote and applied for

12

separate research grants all of which

were unsuccessful

and then finally 13th time lucky i

received my first grant

in 2018. it was a year later

that we received 15 million dollars from

seppi

the coalition for epidemic preparedness

innovations

this was to use the clamp technology to

establish a rapid response vaccine

pipeline

the idea being that we would have three

years to put in place

everything that was required so if

hypothetically the world was

confronted by a global pandemic we would

be ready

we were just one year into that project

when the world was confronted with the

perfect storm of the virus

one that could spread silently before

people even knew they were sick

one that was just mild enough in the

majority of people

that some within the community would

deny it was even a problem

and one that would go on to cause the

hospitalizations

and deaths of millions of people within

2020

this was covert 19. we had only just

hired and trained our new team and set

up our new lab

we had never even produced a vaccine for

a clinical trial

in any other year and by any other

definition we were not ready

but we had a bunch of scientists and a

plan in place

and we were willing to give it

everything that we could when reports of

the new

virus first emerged none of us thought

that it would explode the way that it

did

at first we thought of it just as a good

means to test out new technologies that

we were working on

on january 12th when the sequence of

this new virus was

released by chinese authorities we could

get to work

you see to start our process for

producing a vaccine

all we need is that sequence of asgs and

c’s and t’s

that encode the virus dna on the very

day

that the sequence was released we

submitted an online order for dna

and six days later a bunch of tiny tubes

arrived in the mail

and we were away for the next four weeks

we worked in shifts

with stacks of lab consumables piling to

the roof

notes and lists and codes were scribbled

on paper

so we could keep track of what we were

doing whatsapp messages were flying

amongst the team

so we could coordinate tag team

activities

so we people could sleep without the

work pausing for a minute

in those four weeks our view of the

unfolding outbreak

quickly changed from this is a good test

case

to oh this is a real thing

in those four weeks we had no idea

whether what we were working on would

actually work

or whether we would fail when it came to

the crunch

a phrase that constantly circulated in

the lab was there are no guarantees in

science

we’ve produced and screened over 200

versions of the vaccine over those four

weeks

to select the version that was easiest

to produce at high levels

and that was likely to be the best match

for this new virus we knew little about

we had to weed out any versions that

wouldn’t work i was

we knew there was a little time later on

to come back and start again

we also knew that any improvements we

could make in production

would likely translate to additional

doses available down the line

on valentine’s day february 14th just 35

days after the sequence was

released we had selected a lead and

produced just enough vaccine to immunise

mice from then on it was one thing after

another every day was a roller coaster

ride of ups and downs

there was a thousand different problems

to solve and a thousand different ways

in which the project could fail

our team grew constantly over this time

with us needing to bring in experts and

collaborators across all the different

areas

we have collaborations with anu

university of melbourne

csiro and many private companies who are

with us

every step of the way by this stage our

team was not just limited to scientists

there were many other people working

around the clock to make this dream a

reality

the university’s legal team were working

in overdrive

to put in place all of the legal

agreements that underpin this work

117 separate legal agreements

were drafted negotiated and executed

over this time

our finance team needed to keep track of

all of the donations coming in from many

different sources and being

spent by us just as quickly over 20

million dollars was being spent on this

work

the comms team as well will run off

their feet with hundreds of articles

being published on the uq covered

vaccine

throughout it all we watch the case

numbers and death toll climb

already by april 7 000 people were dying

every day

that weight weighed heavy on all of us

how could we move this along more

quickly was weighed up against the

knowledge that healthy volunteers would

be needed for testing

if we got anything wrong they would be

the ones who could be harmed

the stakes were as high as they come as

any potential mistake could jeopardize

the already shaking public confidence in

vaccines

any negative outcome could not only

affect our vaccine

but could extend to the other vaccine

developers working on the same thing

with the eyes of the world upon us a

negative outcome

could also impact the well-proven

vaccines that are currently in use

by july we had this this is a dose of

the vaccine that was used in the

clinical trial

this was a mammoth achievement that is

completely invisible you can’t see the

vaccine

because it is smaller than the

wavelength of light

to see this vaccine you need to use an

electron microscope

that will fire a beam of electrons

through the sample

but by using this technique we were able

to generate this

this is a 3d model of the vaccine almost

down to the atomic scale

by using this technique we were able to

see that the vaccine is in the exact

same shape

as the spike on the surface of the

coronavirus

this part here on the bottom is the

clamp holding the three molecules of the

spike together

in each dose of this vaccine there are

15 micrograms of the protein we designed

that’s 15 one thousandth of a one

thousandth

of a gram that’s as much as if you took

one single grain of salt and cut it in

four

and said oh no i don’t like a lot of

salt and threw three pieces away

15 micrograms is not a lot but in actual

raw numbers it equates to 15

trillion spiked molecules that’s 15 with

12 zeros after it

15 trillion spiked molecules

sitting in a syringe waiting to be

injected into somebody’s arm

because it is such a minuscule amount

one quarter of a grain of salt of a

highly purified protein

we need to include an adjuvant otherwise

the body wouldn’t even recognize that it

was there

the adjuvant is what triggers a

dangerous signal so that your immune

system

will mount a response against the

vaccine

the adjuvant we use in our clinical

trial was mf59

this is a organic compound produced from

shark liver oil

mf59 has been used in flu vaccines for

over 20 years

and over a hundred million doses has

been given so it has a well and truly

proven

safety track record in the clinical

trial when we tested this vaccine

we were able to show that it was

completely safe and it seemed to work

well

75 of the participants who received this

vaccine

generated a neutralizing immune response

that was more effective

than the average covert 19 patient and

in just under 40 percent

of participants there was an immune

response that was twice

that level however there was a problem

the client component at the base of the

molecule was creating an immune response

that was being picked up on some hiv

diagnostics

participants in the trial were testing

positive for hiv

even though they didn’t have hiv

throughout this year

the team had worked their way through

thousands of different problems

but this was one we hadn’t foreseen it

could be fixed but it would take

time and means starting over up until

then we

hit every timeline we set for ourselves

through sheer determination

and by telling ourselves that even a

single week’s delay

would mean lives we couldn’t save we now

have tens of millions of doses

of a covert vaccine in freezers ready

and waiting

but to use these would mean disruption

of the systems put in place

to detect people still being infected by

another pandemic

the hiv pandemic has been raging for 40

years

and 33 million individuals have lost

their lives

in addition many people may think that a

false positive for hiv

is not a big deal in exchange for

protection against the much bigger

threat that is covered

however there is still stigma associated

with those three letters hiv

and there’s no real way to know how

those negative effects

could flow on to this vaccine program

and as well as others we have therefore

stepped back from our efforts to develop

a covert vaccine

however we will be even more prepared if

or when the next pandemic occurs there

are many other viruses without a

treatment or vaccine

for which our next version of this

technology could

and i hope will be effective this year

has been a roller coaster ride

it’s been intellectually stimulating

challenging

and at times frustrating it has been

emotionally and physically draining

beyond anything i could have imagined

but watching my colleagues within

australia and around the world

rise to the challenge has been inspiring

and has affirmed in me that science is

the place where i want to be

to make a positive impact in the world

the recent developments that a place to

hold on our vaccine

do not change that or diminish it in any

way

science can save lives and change the

world but science is hard

you won’t get it right every time it

won’t go the way you expect or the way

the world hopes

but the important thing is that when it

doesn’t go your way you pick yourself up

dust off your lab coat and give it

another shot

you