all right hi everyone hi defcon
my name is alex hoekstra i am a
molecular biologist and i'm one of the
co-founders and scientists at the rapid
deployment vaccine collaborative or
radvac
i'm excited and i'm grateful to talk to
the biohacking village about open source
technology and vaccine development
building the kind of tools that fill
gaps in global vaccine infrastructure
my goal in this session is to present
the case for open source vaccine
development
and the tools that enable that kind of
development which uh radvac we've begun
to think of as developer kits or vaccine
developer kits
because it's very clear that vaccines
are a uniquely important tool in
biosecurity
and there's so much more room for
improvement in various facets of
vaccinology especially with regards to
accidents
we think that many aspects of vex
analogy should and with the right kind
of tools can be made more accessible for
more people in more places around the
world
and that the
vaccinology itself
uh could grow and be improved uh by that
kind of inclusive participation
so during the kobe 19 pandemic obviously
all kinds of gaps revealed in public
health infrastructure and biosecurity
and there's more reason than ever to
think seriously and creatively about how
to fill these various gaps going forward
uh i guess both for uh the ongoing
reality um
for billions of us um still struggling
through kovid
and this pandemic but also for
inevitable future emerging diseases
which we might be able to minimize and
even prevent the right tools
so i want to introduce some work by
discussing some concepts regarding
vaccines that i think me will be
familiar to a lot of people here who are
already familiar with space but i also
want to get into some hopefully
exciting and new ideas for a lot of
people across the biosciences
um since vaccinology has been heavily
shaped by iip laws
for the last seven or so decades
there's a lot of room for creative
improvement
especially when you begin thinking kind
of outside that box
i think it's important to bring up a few
foundational topics like vaccine
economics
and and the unique role of the vaccines
play in epidemiology and uh as well as
as the immunology as it relates to uh
vaccine platforms or the technology
themselves so we'll take a quick look at
those issues before um we get into you
know what radvac's doing in particular
because i think they're helpful in
identifying the gaps and why they exist
presently
um ultimately i do want to get into uh
what we've been doing at radvac and in
terms of open source efforts uh what
open source efforts can do to kind of
bridge those economic technical and
logistical gaps
uh we at radvac have been working on
building a particular platform for
intranasal uh peptide-based vaccine
candidates against cyrus co2 virus
um
but we also think that uh these these
principles of development may be more
valuable in their generalizable form
than any single
um development project on its own
so i want to get into why vaccines are
uniquely important uniquely leverageable
tool in public health and defense
against infectious disease
vaccines serve to combat disease in a
number of ways primarily by inhibiting
infection inhibiting disease inhibiting
transmission and inhibiting replication
which subsequently
inhibits mutations and the evolution of
new pathogens
and although there are a variety of
important and even very useful tools to
achieve some of these functions factines
are arguably the most important
this swiss cheese model uh is something
that i'm borrowing in mckay who adopted
a
similar illustration for covid another
mine uh is only showing a handful of
risk prevention interventions
and isn't really to scale in terms of
each interventions efficacy it's
stopping pathogens from infecting a
person uh i think the illustration is
still a useful one insofar as
uh it makes the case for applying
multiple layers additive layers to
mitigate
vaccines though are unique among these
interventions because they both augment
a person's ability to fight off
infection if the prior layers of
protection fail
but also if applied at scale across the
population vaccines can limit the
collective exposure to these pathogens
by reducing the number of available
hosts and transmitters and in the next
slide we're going to get into just a
little bit of math i promise it won't be
uh it will be too much and that'll be
the end of the math
um
but essentially the network effects may
be one of those important features to
vaccines
which are good on a personal level right
good for individual health but so much
better
on population scale
right but a lot of things have to go
right in order to achieve those
population scale network effects uh and
as of now as of july 2021 almost a full
16 months after the first coping
vaccines were actually developed and now
seven months after those vaccines were
authorized and made available in the u.s
and other high-income countries were
still not yet achieving the full benefit
um or benefits of those network effects
on disease prevention
that these vaccines could
and hopefully will soon provide once
they're made more accessible and more
widely deployed
so there's a good amount of math
involved with
uh considering how to prevent or
independent
accounting for things like population
characteristics age health status
mobility environmental conditions uh and
a lot more but one of the most important
concepts is understanding the effective
reproductive number for a given disease
effective reproductive number is
sometimes written as r or r sub e uh and
it's a bit different from basic
reproductive number which is uh you know
more commonly talked about it it's
r naught or r sub zero
um
because uh effective reproductive number
uh r sub e uh basically takes into
consideration the percentage of a
population that's susceptible to
infection essentially the percentage uh
that is not immune
um
sometimes written as s so our knot on
the other hand is uh is meant to be a
metric of a disease's contagiousness or
transmissibility now you can calculate
effective reproductive number by
multiplying the basic reproductive
number by s
so killing a pandemic requires
bringing that effective reproductive
number to under one
since the spread of infectious disease
is essentially an exponential function
in which every infected person can
infect a certain number of other
non-immune people
a reproductive number um a reproduction
number uh greater than one will increase
the transmission at an exponential rate
whereas the reproduction number uh below
one decreases transmission approaching
zero new infections uh over time
so here we can see a few illustrative
graphs and what happens to an
exponential function when that when that
constant um
is above one and when it is below one
um so the state uh is is related to a
herd immunity threshold hit
which is also a function of a disease's
reproductive number
essentially the higher the reproductive
number for that disease
the higher the threshold for population
scale immunity
the population is immune to a disease in
excess of that diseases uh immunity
threshold
the number of cases reduces at a faster
rate outbreaks are less likely to happen
and outbreaks that do occur are smaller
than they would have been otherwise
it's probably important to note that
the herd immunity threshold doesn't
represent the point at which
a disease stops spreading altogether but
rather the point at which each infected
person infects fewer than one additional
persons on average
essentially modulating the effective
reproductive number and diminishing
the incidence of disease
so these are useful formulas when
thinking about vaccine readiness and
roll out in situations of emerging
disease where populations begin with
virtually no pre-existing immunity
so the effective reproduction rate is
actually very high
and can be brought down by vaccines that
are both effective and very importantly
available
so what happens when there's no uh
pre-existing immunity so s is very high
and we're met with a disease that has a
high basic reproductive
well we are living it with uh soros cove
too
uh since sarco 2 is a new virus and
since it replicates with with high
efficiency covet 19's debut has been
devastating
um cohen's toll on human health won't be
fully calculable for years now
but uh you know because we're still very
much in this pandemic globally where
immunization rates are low and the
effective reproductive rate
is greater than one in many places
again no no matter how effective a
vaccine is on an individual level uh the
key to ending pandemics is decreasing r
uh that effective reproductive rate now
which means decreasing the number of
acceptable non-immune folks s
so bear in mind that uh the production
authorization and rollout of safe and
effective vaccines for an emerging
disease in under a year
is historically unprecedented and a very
very good thing but it's also clear that
the costs of not being prepared both in
terms of prevention and in response
those costs are vast and indeed far far
greater than the cost of building the
kind of biosecurity infrastructure
including vaccines
that were
you know we already largely know how to
make
so i'd like to explore why this
infrastructure was lacking uh and then
maybe get into some solution-oriented
ideas
i think it's important also to talk
about the ecosystem of vaccine
development that existed leading into
2020 and why covet caught us all off
guard despite years and years of
scientists and people who listen to
scientists agreeing that such an
outbreak was really only a matter of
time
so professor andrew lowe um at mit uh
professor of economics there has done
some really interesting analyses on the
economic landscape of vaccine
development over the last few decades
which taken together revealed some
interesting insights about why despite
their importance and despite the high
rate of technical success in development
uh vaccines are less than 10 of
industrial biotech investment
um it turns out the vaccines have a
uniquely high probability of
success and and develop close to 40
compared to 11 across all therapeutic
groups but industrial sponsors have been
pulling out of the vaccine development
business for
at least the past two decades
so professor lowe and others began to
understand that vaccines are a high cost
and low financial reward low margin
investment
and generally a turn off for industry
industrial or industry sponsors biotech
pharmaceutical companies as well as
their
investors dr lo and his colleagues point
out that these um analyses of vaccine
landscape um
reveal some some big gaps in investment
waning vaccine r d participation uh and
ultimately in inhibited vaccine access
uh that predate 2020 by a number of
decades
um and they suggested public sector
support may be useful in filling in
these gaps left by kind of a lack of
capital market incentives
and this itself is a really interesting
line of thinking because with what we
know about how vaccines leverage network
effects at a population scale lowering s
lowering r
by increasing immunity throughout that
population we can ask
could vaccine development and vaccine
innovation be driven by sort of
rethinking of vaccines not as a
market-dependent good
but instead as a sort of international
public since they clearly have
international public benefits and since
the market incentive structure has
failed to make those investments
profitable for profit-driven developers
so far
anyway the need for public sector
support uh should probably include
scientists many of whom also happen to
be members of the public many of whom
may actually be listening right now
um so vaccinology is is really a
constellation of a dozen or so
disciplines in the field of science
including public health epidemiology
immunology psychology chemistry
economics uh policy clinical trials
ethics informatica we've actually had a
couple of physicists reach out and offer
to assist us in characterizing uh our
vaccine candidates so it's clear that
there's a need for skilled people of all
kinds to take an active part in building
global scientific and logistical highway
system
that can deliver vaccines to populations
more quickly with high levels of
efficacy safety trust
and access
but we at radvac took a systems view of
the gaps in vaccine infrastructure and
across four different elements
of the vaccine response including r d
testing approval and deployment of
vaccines it seems to us that
each of these steps could be potentially
augmented improved sped up and made more
accessible globally
by increasing the kind of access that
empowers participation in each of those
central processes
we believe that the ability to take part
is a fundamental prerequisite for things
like vaccine equity inclusivity
transparency
ultimately in trust safety efficacy as
well um and ultimately in in developing
great ideas about how vaccines work both
on a technical level but also on a
systemic worldwide people and global
health level
radback actually began when dr president
esa sent out an email asking me and some
of our other colleagues if any of us had
heard of projects to accelerate vaccine
development through public participation
potentially citizen science he figured
that since vaccines are fairly old and
fairly well understood technology
uh or at least that many vaccines were
built on very well established
technological platforms
and might not be out of reach from
vaccines to be developed quickly even on
a low budget
maybe even with you know massively
parallel distributed um you know kind of
a global scheme
uh several of us got really interested
in the idea and we formed the core of
the radvac team so i'd love to tell you
what we've been working on
um so we began with a couple uh
principles in mind um
you know uh because of of decades of
extensive research on both pathogens and
on the development of vaccines
modern vaccines are actually very quick
and easy for experts to develop um they
they have again by far the highest
probability of success of any
therapeutic class
so access to vaccines and the process of
developing vaccine research and
development vaccines
is presently prohibited right it's
expensive uh it's fairly well guarded by
uh intellectual property again relating
to the expense and investors having to
recoup
their investment but
we we think that that
participation should be enhanced and can
be enhanced through open source
information
uh research and resource sharing
um and and
you know one of the the most powerful uh
principles motivating principles for us
was that you know in this this crisis we
we should help right we should do
something uh rather than waiting for the
status quo rather than waiting for um
you know the uh
sort of authoritative pre-existing
infrastructure to do its thing
and uh
and so we did we are you know we are
trying uh and we will continue to try
and um you know
our method of trying uh has a
kind of a unique structure to it um
which is sort of intrinsically open
source open source is kind of a central
component of our our development
platform
um
when we say free and open source we mean
it both in in three like speech industry
like beer that is the libre and the
gratis definition
but essentially it's it's um
you know it's meant to inspire this sort
of uh positive feedback loop of uh
researching prototyping refining sharing
and then getting feedback from um other
collaborators and you know throughout
this this uh sort of shared challenge
um
we took into consideration some some
sort of basic
design principles um when considering
how to develop vaccine candidates that
fit
the needs of this pandemic and
potentially future fantastic so
we opted for um you know safe
inexpensive accessible and primarily off
the shelf materials very few custom
components
and very few that required sort of um
you know
i guess high-grade or or
inaccessible laboratory infrastructure
we also wanted these um these prototype
vaccines or vaccine candidates to be
rapidly reproducible
that is rapidly producible but also
you know with high enough fidelity and
enough simplicity that they could be
reproduced in other labs so that you
could have sort of parallel
implementations and maybe parallel
experiments happening in multiple places
at once
obviously um you know for for that to
work uh it has to be safe uh both in
terms of development which means no
infectious components uh and also on the
sort of administration side
which you know also if you are working
with safe materials it certainly helps
with safe administration although those
two aren't totally equivalent
we also wanted well characterized
antigenic targets which could ideally be
adapted over time as
as more research began um to to focus on
the selection of certain epitopes that
elicited the strongest or the best or
the most um sort of uh
immunologically useful responses from
host's immune system and and
you know all encompassing within this is
the idea that this work should be shared
right and that it shouldn't be contained
to a single laboratory or a single team
or a single brain
it isn't necessarily against
um
the traditional model but it is
potentially enhancing of the traditional
model right that um and we've seen this
with other open source developments in
other areas right that um
the android operating system leverages
open source technology but google still
makes
a good amount of money
either on android or
android components so you know this is
not an anti-profit model it's not an
anti-revenue it's not an anti-business
model it is a pro-sharing uh and sort of
pro-accessibility model
so
um
in order to catalyze that participation
uh in mid 2020 we we published our first
white paper describing the initial
proposed vaccine candidates against
stars code two
we had four authors uh the original
white paper was 43 pages with 84
references
19 peptide sorry 19 epitopes uh uh from
stars cove 2 that were identified in the
research uh or predicted in other
research
to be of high value
in terms of eliciting uh immunogenic
response from the host uh we also um
you know gave kind of a primer
background research um and provided this
sort of library of pre-existing research
on mucosal and cellular and humeral
immunity um
again epitope selection and
immunogenicity and resilience against
future variants by selecting for
conserved epitope
you know we also went into uh you know
not a great length but considerations
for safety and efficacy testing for for
uh
short and long term uh for shelf life
and stability uh for booster doses and
uh and for ethics we think that's
important during a global crisis like
this
so as of 2021 that's july of this year
uh we've released over a dozen updates
to our white paper
we have more than 20 authors uh 90 pages
more than 200 references we've uh
updated and in many ways narrowed uh our
list of uh of well-characterized
epitopes that we think are um
uh you know highly useful and eliciting
uh an immunogenic response uh against
stars cove two and protective against
cope with 19.
um
along that line we've produced 10
generations of vaccine candidates
um
so far uh we've expanded our discussions
on safety and advocacy
and an epitope selection and booster
regimens and heterologous bluetooth
regimens
um optimizing production optimizing
stability optimizing sort of um valence
or multivalence where we uh we talk
about sort of the breadth of immunity
that's provided by a vaccine and whether
it is resilient against these uh
future variants and mutations that might
otherwise um
you know
minimize vaccine efficacy
but really you know it has become
a a collaborative living document and uh
and catalyst
for collaborative living research
so
i mentioned earlier um you know some of
the parallels uh in in other
open source development and open source
uh initiatives um
linux for instance uh is you know kind
of a great example of how
uh we hope we might be able to
contribute with uh with developer kits
right so linux clearly um
is is such an infrastructural tool in uh
software development and hardware
development and really promoting
accessibility for uh most of the world
at this point and and it's clear that uh
you know there are reasons that linux is
superior to alternatives uh that have to
do with uh its open sourceness right its
collaborative development ecosystem um
and uh the ability for for multiple
people in multiple places uh to take
part without restrictions
so
um
you know uh we conceptualize um
uh viruses as sort of non-digital
pathogen kind of funny because the name
went the opposite way right so uh
computer viruses are the digital sort of
um appropriation of the actual
biological virus so we're kind of going
in the opposite direction now
so in software developer toolkits you
know there's a number of key features uh
that are really useful right um uh that
may be required in order for people to
actually like use them and pick them up
and uh and develop cool things with them
so uh chief among them are a compiler a
debugger uh and a software framework um
and some of the components that um you
know are critical are libraries
documentation code samples processes and
guides and we think that the vaccine
developer toolkit should should mirror
uh and encompass all of those components
that are essential to
collaborative and open source um
and even just good vaccine development
again like um in open source you don't
have to necessarily share and share like
right you can take it um and if you
adapt it well enough you can actually
even patent it you can protect it with
ip
um and and even when it is open source
there's no real reason you can't uh
start a company right uh you you
you know you can run with these products
in a profit or even revenue driven way
but to put it in context of vaccine
development we think that providing a
framework of reproducible
simple accessible adaptable vaccine
technology
is really useful
in terms of processes we want detailed
production protocols in terms of
libraries we want you know vast
documentation of past studies that are
related to
vaccine immunogenicity vaccine safety
various aspects of vaccine technology
the code samples for us come down to
the design specifications for specific
vaccine candidates
in terms of debugging vaccine candidates
you got to talk about protocols and
considerations for pre-clinical and
clinical testing
and ultimately it has to play well with
others we think
um and and you know this is achievable
through open source licensing like
creative commons um and through an
active
engaged uh you know developer ecosystem
um and ideally one that is committed to
this concept of working together or at
least learning from one another
as they each do maybe their own thing
so you know along that line um we think
that our white paper is kind of a
foundational open source vdk right a
vaccine developer kit and um it may be
that uh there's there's huge room for
improvement in the the construction and
the composition of vdks there are
certainly components of the white paper
that uh you know don't exist yet right
we um
we've done a lot to characterize uh our
our method of epitope selection um
and and you know various other things
that i've ever talked about but like um
it still kind of lives in a pdf right
and and um
i don't think pdf is necessarily
anyone's preferred format of engaging
with
um a project right or engaging with uh
you know it's not necessarily a
collaborative
ecosystem in and of itself so
we've started um a researchers map uh in
hopes of connecting people who are are
interested in doing uh vaccine
development together um or learning from
one another or uh you know sharing ideas
sharing resources and that kind of thing
but really it's in its foundational
stages and uh what i hope to achieve
here uh you know
is
both to to
pitch the the idea that
open source vaccine development is
useful
and achievable um but also that uh
you know it's worth your time right that
it's worth the uh
the engagement uh and the efforts of
people of all kinds of skill sets
um
so i think that we're at the beginning
um i think that we're we're facing
you know a variety of possible futures
but one of which is of open source
infrastructure for vaccine development
and essentially that infrastructure
extending the ability
to participate in vaccine research to
historically
excluded people right um and
you know the the the costs of exclusion
the costs of exclusivity in vaccine
development are things that we're
feeling um you know very acutely during
the covet 19 pandemic um but also that
uh you know unless we resolve them are
not going to be fixable uh with the old
way of doing things
so uh you know it's interesting then to
think about what would biosecurity look
like if it were decentralized right from
these sort of centralized nodes of
pharmaceutical companies uh with very
very high budgets um or potentially
their budgets um doing you know the
majority of these uh you know these
developments
um what if we were able to decentralize
that a little bit by bringing down uh
certain infrastructural costs or
infrastructural barriers the bdks i
think are are a way to make vaccinology
easy affordable accessible and for
people who want to
start vaccine companies which may be the
only way to get to a billion doses
i think again by reducing those costs
we can
we can get more people involved we can
see more vaccine innovation we can see
better vaccines that could get developed
and approved faster
and more effectively
so uh with that i thank you i hope uh
that uh that you got something out of
the presentation i hope that you'll uh
you'll get curious about what an open
source vaccine development future might
look like uh reach out to us at
randomvac.org
[Music]
or elsewhere
and thank you for your time