The trials tribulations and timeline of a COVID19 vaccine Jerome Kim
perhaps I can begin just simply by
describing vaccine development I mean at
its heart vaccine development is a
relatively simple concept first you
prove that the vaccine works is safe and
effective
you make the vaccine and then you use
the vaccine and usually we have five to
ten years to actually prove that the
vaccine works to make it develop it and
do all these things that comes at a cost
of about a billion dollars and has a 93
percent failure rate but under the
pressure of this pandemic with eight
million infections and four hundred
thousand deaths you know we’re being
asked to speed the process up and to do
this work that normally takes five to
ten years in 12 to 18 months so to cut
to the bottom line up front can we prove
that a vaccine works probably it’s
likely can we do it in 12 to 18 months
that’ll be tougher but if everything
works possibly yes can we make it in
sufficient quantity with sufficient
quality and at an affordable cost that’s
a tougher one and finally we’ll be will
we be able to use it with equity and
access for all and that’s possibly the
toughest one of all but that’s the one
that is the question that will bring us
to the end which is a significant
reduction in kovat 19 burden and disease
that will result in alleviation of the
suffering that this pandemic has brought
to the world
thank you for that dr. Kim and our
audience will jump in with questions
soon I’m sure but I have one for you too
kicked us off you know you worked on the
HIV vaccine and obviously that has been
a multi-decade effort and we still don’t
have one what gives us confidence that
it will be different with this
particular corona virus that is a great
question and there are a couple of
reasons why I think that we will
probably be more successful and sooner
with the corona virus vaccine the first
is actually something that we don’t have
the full answer to I’m still a largely
unanswered question but I think we
probably are gaining enough information
to make a reasonable response and that
is with a with the typical disease say
measles or hepatitis A after you acquire
the infection everyone has a slightly
different course but in the end your
body’s defense system the immune
response is capable of controlling the
virus eventually eliminating it from the
body and those same protective responses
do not allow the virus to come back so
you have immunity or protection from
reinfection that is not the case with
HIV with HIV and to some extent with TB
an initial infection can be followed by
re infection and that reinfection really
indicates that the immune responses that
are developed normally in the normal
human body to infection are insufficient
to get rid of the disease but even more
important to protect against reinfection
with kovat I think there’s increasing
evidence that people who have been
infected are at least for a period of
time protected against reinfection and
that’s actually a very critical concept
the second part is and it comes from
animal models you know we we have or we
often say as vaccine developers that
mice lie monkeys exaggerate and only
humans tell the truth but really the
monkey model is the closest thing that
we have
to to a proof of concept before we
actually test the vaccine in humans and
now there have been three reports of
tests using the current of human
vaccines against kovat 19 protecting
monkeys against challenge and so that
would mean that at least in a non-human
primate system which is what monkeys are
vaccination can protect against
infection and that’s actually a very
important proof of concept so next onto
people so let’s break that down a little
bit there seem to be hundreds of vaccine
candidates what are the what are the
approaches but they they all sort of
take different approaches what are the
main approaches we’re taking with these
vaccines okay there are two that were
very fast that we called them nucleic
acid vaccines and they are RNA and DNA
so you remember from biology that when
you start with a gene which is DNA in
order to get that gene made into
something you actually have to use
something called RNA so it goes DNA to
RNA the RNA is then translated into
protein which then becomes the material
from which we can either create new
parts of the body or create other
structures in the cell or make things
that will develop into those structures
and so the two vaccines that were
started first were DNA and RNA and
actually within a few days of the
sequence of kovat 19 being published
companies that make DNA Narvik DNA and
RNA vaccines are reported to have
developed the concept for the vaccine
and within a week they had made the
vaccine and shortly thereafter they had
injected it into animals and so the
first of these roughly eight weeks after
the initial announcement of the sequence
of the virus entered testing in humans
and that was the RNA vaccine from Adana
so those tend to be fairly quick DNA and
RNA and actually in april the test of
the DNA vaccine made by inovio in humans
started as well so again very fast
development process the next set of
vaccines that were out there were with
what we call vectored vaccines
these are little pieces of the genetic
information of the Cova da virus
inserted into another virus and one of
the more commonly used one is is a
common cold virus called adenovirus and
the adenovirus
type five is the basis for the chinese
Kansai no vaccine a chimpanzee
adenovirus is the basis for Oxford’s
vaccine which is now being taken over by
AstraZeneca and an ad type 26 vaccine is
the the vector for the vaccine that
yangsun is making which is a part of
Johnson and Johnson the next set of
vaccines actually are actually
conceptually easier to understand these
are what we call whole inactivated virus
vaccines and in a whole inactivated
virus vaccine you introduce the back the
virus into cells the virus grows as it
normally would you harvest the virus
from the culture medium and then you
purify it and kill it with heat or
formalin or other chemical substances
and those hold inactivated virus
vaccines you know are relatively easy to
make they’re relatively cheap and we
have examples of them you know the
inactivated polio virus vaccine for
instance as a whole inactivated vaccine
so each of the concepts has strengths
some of the concepts are faster than
others but really you know we have a
host of proteins of vaccines now
entering the second stage of testing in
humans which is incredibly fast and
great news as well well I believe we
have some questions from our audience
I’ll take the first one if we can fade
that in on the screen below stand by for
a second
I know the questions are out there it’s
just a matter of getting it on screen Oh
looks like we’re having
be having some check
difficulties but we’re back
well I guess I will ask another question
oh here it is I guess we’re not going to
be able to fade it in an on screen it’s
a question from Kevin from our community
what do you think the effective rate of
the first vaccine will be almost
impossible for me to tell we’re
targeting something above 60 to 70
percent and the reason it’s difficult to
tell is there hasn’t been much data put
out yet
I mean we’ve advanced a Phase two we’ve
seen some of the data for protection and
monkeys but we’ve seen relatively very
little data in humans we heard moderna
report on eight out of 45 of the people
in their phase 1 trial we’ve started to
see some data from Cansino
which is an ad 5 based vaccine but it’s
actually been difficult to form an
opinion because there there actually
hasn’t at this point been a lot of data
published based on the human trials you
know we’re starting to see some small
animal data you know from inovio which
is a DNA vaccine and from moderna small
animal data which is an RNA vaccine but
again this makes it a little difficult
to prognosticate but I would guess that
you know you’re going to need to see a
fairly significant effect and actually
it’s not only the the actual number but
how reliable that estimate is and and
that’s the thing that the US FDA the
European equivalent of the FDA and the
w-h-o have been pushing that we really
need enough precision around the
estimate to really make a clear
statement that this vaccine actually
works and is safe yes in the meantime
wear masks all right the next question
comes from Frank Hennessy CO and you can
see it there at the bottom of the screen
so the technical difficulties have
dissipated Kovan 19 seems to affect
different people in different ways
how do you select a vaccine that is
effective for everyone so that’s
actually another great question but if
you look at different diseases different
diseases affect people in different ways
kovat is actually very interesting
because eighty percent of people are
either asymptomatic or have mild
symptoms you know fourteen or fifteen
percent of people have significant
symptoms five percent of people get very
sick and two to three percent of people
die that’s actually you know a pretty
reasonable distribution of illnesses and
I mean measles is the same some people
have very mild symptoms have the rash
other people get much sicker and some
people actually have severe
complications from measles and you know
in places like Madagascar or in the
Democratic Republic of Congo children
die of the measles so again you know but
a single measles vaccine protects us all
and I think that’s one of the other
things about vaccines you know when we
think about treatments and antibiotics
resistance develops fairly quickly to an
antibiotic but we’ve had measles vaccine
for decades and there isn’t resistance
to it
so again resistance develops more slowly
to vaccines now the one exception might
be influenza vaccine and we don’t know
whether kovat is going to go into
influenza like mode or not and that’s
one of the things that we’ll know more
about in a year or two years or three
years as this epidemic matures but by
and large you develop a vaccine against
measles mumps rubella hepatitis A
hepatitis B and that vaccine will work
for a very long time one of the greatest
public health interventions in world
history so our next question comes from
Laura Pearson my biggest concern with
vaccines is side effects is it possible
to test the long term side effects in
the short term and if so how so when
you’re developing vaccines the one of
the critical features is is efficacy
whether the vaccine actually protects
against infection and disease the other
critical parameter is safety most of the
side effects that we can look at instead
and clinical trials occur within the
first month to three months of or well
occur immediately or in the first one to
three months after the vaccination the
longer term side effects actually
require much longer periods of time and
sometimes much larger populations in
order to see the effect so government
regulatory agencies like the FDA or EMA
have set up systems to sir to provide
surveillance for adverse of events to
pick up rare adverse events and so
that’s a very important question
but given the number of people that will
be involved in the testing we should be
able to detect the relatively shorter
term short to mid-term effects though
out to roughly a year or so it at vary
actually at relatively low levels so
under 1% so hopefully we will continue
to collect safety data for the period of
observation which is for clinical trial
typically a year to two years we will
continue to collect information because
these vaccines in particular are being
pushed towards efficacy and I think many
of us understand that as vaccine
developers the other and very critical
part of what we have to do is ensure
that we have vaccines that are safe so
but a great question yes and I wonder if
this will be a vaccine where you know
you need to get it every year like
influenza or you require a booster at
some point or because that will also
affect my my real question which is
about kind of manufacturing and
distribution obviously if it’s one shot
and done then maybe you need just seven
billion doses if it’s if it requires a
booster we’re starting to get into some
really crazy numbers how are we gonna
manufacture and distribute these
vaccines dr. Kim yeah and I you notice I
enough that part of the question blank
and the reason is you know so normally
when you’re doing a vaccine development
the last few years of your five to ten
year cycle your plan
the manufacturer because you’re already
in phase three and if you’re a vaccine
company you don’t actually make any
money on a vaccine until it’s sold so in
the final year your two years of testing
you’re in the process of making sure
that you can have enough available early
on so that immediately after approval is
given you can move to sales that would
happen in five to ten years now we have
12 to 18 months and where do you start
planning the manufacturer so operation
warp-speed which is the US government
program is already saying that they may
actually make vaccine at risk and what
does that mean it means that while we’re
beginning the testing the government
will be manufacturing doses of vaccine
at risk not knowing whether the vaccine
works but just so that those vaccines
that have entered the final stage of
testing when and if they’re shown to be
safe and effective
there will be doses of vaccine available
for use and that’s actually a remarkable
thing and it happens and it can happen
it doesn’t normally happen but it can
happen this time because the US
government is underwriting the risk for
the manufacturer of vaccine so if you
were a company you wouldn’t do things
completely at risk you’ve usually gone
back you’re pretty sure that what you
have in Phase three is going to work
because you don’t want to waste time and
money on a vaccine that isn’t going to
be safer effective what the US
government is saying is look this is an
emergency and because it’s an emergency
we are willing to carry some of the risk
and that allows the company then to
start manufacturing before they actually
know other organizations are planning a
similar strategy so as you’re rushing to
do the what we call the Phase three
trials the tests of efficacy and safety
at the same time companies are going
around the world to identify partners
because they know that they in an
individual company might not be able to
make a billion doses but if they partner
with people in South America and India
and Korea or Japan they might be able to
put together enough manufacturers to
make enough vaccine so that over time
we’ll be able to produce the seven
billion doses that are required if we
only need one shot if we need
two shots that could be 14 billion as
you pointed out and if we need a late
booster that would be even additional
billions but you know the problem of the
duration or what we call the durability
of those protective immune responses
really we won’t know until we look at
the curves of decay and we understand
what the protective immune response is
something we call a correlative
protection and those are actually going
to be really important because once you
have a correlative protection you no
longer have to do a phase 3 trial in
30,000 people you can do a much smaller
trial much faster and really look to see
whether a new maxeen or a modification
of the vaccine which may be better
develops that particular lab test what
we call the correlative protection and
that really shortens development time
and and decreases the cost and so one of
the goals of the activity that’s going
on now is both to show safety and
efficacy but also to try to identify
what we call the critical correlative
protection so even with that kind of
development of these breweries for
vaccines at risk or repurposing for for
Co good vaccines it seems like we’re not
going to have 7 billion doses kind of
ready to go you know 12 to 18 months
from now how are we or what it in your
opinion is the best way to prioritize
you know who gets the first doses and
where and and all that kind of
decision-making so you know I think that
countries will you know countries
particularly those countries that have
put significant amounts of funding
towards you know accelerating the
development and manufacture of vaccines
are going to want vaccines to protect
their own populations first there you
know there have been commitments for
instance the president G of China has
said the vaccines are a global public
good and that they would share that but
those vaccines with other people the
question is how quickly and on the other
side though we have an organization
called the Coalition for epidemic
preparedness innovations or sepi and
seppia is a is a group of
now what was initially 13 now probably
15 or so countries plus the Gates
Foundation and the Wellcome Trust and
other charitable funders the European
Union for instance and they put together
two billion dollar portfolio that allows
them to develop vaccines very rapidly
they’ve funded many of the companies
that are now moving vaccines into Phase
two and that’s important because sepi
makes a company sign an agreement that
it will provide global access for the
vaccine which is to provide adequate
supply at a reasonable cost and the sepi
group there’s a secretariat and
countries and people who sit on their
board of directors who will help to
discuss the appropriate allocation and
we have to also consider organizations
like the World Health Organization or
the United Nations or other
organizations that actually now should
be talking about what we will do when
and if we have a vaccine that’s safe and
effective because I think is as you were
kind of hinting the time to make that
choice is probably not when you have the
first vaccine that works because when
that happens there will be a huge
pressure to vaccinate us first or them
first or this group first or that
groupers and really if you haven’t made
your choices in advance and you can’t
defend it in a transparent and
principled way it’s going to be there’s
going to be a lot of recrimination and
and perhaps some unnecessary death as a
result of that or unnecessary infections
and deaths as a result of that so we
need to start working now we need to get
together to talk about this well it
certainly doesn’t help that the the u.s.
is no longer participating with the wh o
or or sepi and it seems to me that
health care workers and the elderly who
seem to be most at risk should be maybe
the first candidates but that’s just my
opinion I’ll be interested to see
there’s another audience question I
believe let’s let’s go to that if we can
there we go
when there are multiple vaccines on the
market in
two to three years with varying efficacy
rates and presume no safety signals how
does the world prevent the allocation of
better vaccines to the rich and lesser
vaccines to the poor that’s a very
important that’s a very interesting
question and when we have one devack
scene I’ll be happy when we have three
vaccines I’ll be really really happy you
know we have to make I think as you
pointed out maybe 14 billion doses
that’s a lot of vaccine I mean when you
look at annual production of vaccines
that is tremendous so different
countries in the world will make
different vaccines that happens
currently and there will be some
standards you know the w-h-o is already
developed what we call a target product
profile for vaccines that it will review
and hopefully approved very quickly for
or recommend for use in countries around
the world and so hopefully all of those
vaccines will pass the minimum
requirements that are set both by the
agreements that were put together by the
regulatory bodies the w-h-o the US fda
the EMA you know all the different
regulating body regulate drug vaccine
regulatory bodies in the world came
together and put together a document and
hopefully then there won’t be as much
variation in what we would consider to
be a minimal level of an effective for
effective vaccines