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