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