Download Current vaccine approach (2)

Flu Universal Vaccine
London
5th August 2011
SEEK is a drug-discovery group that uses a pioneering
scientific and commercially-driven approach to create
breakthrough medicines which address major diseases
in order to radically improve human health.
5th August 2011
Low versus high mutation
• Viruses such as chicken pox have a
low level of mutation, so people obtain
long-term immunity from exposure to
the virus
• Previous exposure to flu does not
provide long-term protection because
the virus mutates seasonally
• Vaccines are developed to mimic the
disease, tricking the immune system to
react as if it had encountered the actual
virus in order to develop memory
against part of the disease
• For highly-mutating viruses, this does
not work as memory is formed against
the variable regions
5th August 2011
Current vaccine approach
• Existing influenza vaccines use a
weakened strain of the current
year’s virus
• These vaccines stimulate the
immune system to produce
antibodies as the first line of
defence
5th August 2011
Current vaccine approach (2)
• Antibodies attach to the virus via
some of the surface proteins. Once
attached, the virus is destroyed,
creating memory antibodies
5th August 2011
Problem with current approach
• Certain proteins of the influenza
virus mutate from year to year,
particularly those on the surface,
therefore, memory antibodies
developed from prior years’
exposure are ineffective in dealing
with the current year’s virus
• This is why annual flu vaccination
is necessary and why a vaccine for
the pandemic cannot be developed
until the strain of the virus is
characterised
5th August 2011
Replication of Virus
• Since the virus is not destroyed
by antibodies, it enters lung cells
where it hijacks the cells’
machinery in order to replicate
• Once the virus population
reaches a critical level, the person
will contract the flu
5th August 2011
Cellular Mechanisms
• When a virus enters a cell, it breaks down into peptides, some of which are
exported to the cell surface via molecules called HLAs
5th August 2011
T cell mediated immunity
• T cells form the second line of
defence of the immune system.
They recognise internal peptides
presented by HLAs on the surface
of cells
• Each T cell will only interact with a
specific HLA/peptide combination
5th August 2011
T cell mediated immunity (2)
• The more a peptide is presented
by HLAs, the more memory T cells
are generated that recognise that
peptide. The more memory T cells
that recognise a peptide, the
stronger the immune response to
that peptide
• Mutating viruses tend to produce
more variable peptides. Hence, the
majority of newly-created T cells
are directed towards highly-variable
peptides, which change seasonally.
This is how the virus evades this
arm of the immune system
5th August 2011
New vaccine approach
• In order to overcome the
variable surface proteins,
scientists targeted the internal
proteins of the virus, which are
less variable or contain more
“conserved” regions
• These whole proteins are too
large to make synthetically,
therefore, scientists delivered
them to cells in the form of DNA
via a vector, to get the cells to
make these proteins
• Protein expression levels are
difficult to control and the vector
used to deliver the DNA tends to
favour the cells it was designed
to infect, which can cause
difficulties such as tolerance
induction
5th August 2011
New vaccine approach (2)
• The immune system is left to
choose which peptides from the
whole proteins to memorise
• The immune system produces
the most memory cells against
those virus peptides that are
most abundantly presented on
surfaces of cells. These tend to
be the most variable peptides
5th August 2011
SEEK’s approach
• By examining every human and
animal influenza A and B strain
that has existed over the past
60yrs, certain parts or regions of
the viruses’ proteins that are
conserved in all strains have been
identified
• SEEK identified the most highlybinding and reactive of these
conserved regions to form the
basis of the antigens in its vaccine
5th August 2011
Explanation of SEEK’s approach
• A vaccine made using these
binding and reactive conserved
regions of the virus proteins, the
peptides would enter cells and be
presented in large volumes to the T
cells via the HLAs on the cells
surfaces
5th August 2011
Explanation of SEEK’s approach (2)
• This approach dictates to the
immune system which peptides to
memorise
• By doing so, it does not allow the
normal evading mechanisms of the
virus, or whole proteins of the virus,
to trick the immune system into
remembering the variable peptides
5th August 2011
Immune response
• Significant numbers of memory
T cells are now created against
these constant peptides, as more
are presented on the surfaces of
the cells by the HLAs
5th August 2011
Immune response (2)
• In natural-occurring infection,
these constant peptides would
have to compete with other
peptides for space within the
limited number of HLAs on cells’
surfaces, resulting in fewer of the
desired memory T cells being
produced
5th August 2011
Implication of SEEK’s vaccine
• SEEK’s vaccine would
eliminate the need for both
annual and pandemic
vaccinations
• The constant peptides found in
all animal and human influenza
viruses, represented in the
vaccine, create sufficient
numbers of memory T cells to
destroy enough of the cells
containing the virus, preventing
the contraction of flu
• Due to the large number of
conserved regions used in the
vaccine, the statistical chance of
all the regions mutating is
negligible and, if certain ones
mutated, the virus would be
unable to enter lung cells and
would no longer be flu
5th August 2011
Current vaccine production
• Traditional vaccine production
involves growing the virus strain in
chicken eggs
• A limited supply of eggs, and a
shortage of factories, limits the
maximum production to 350 million
doses per annum
• Given the time to manufacture,
and time to vaccinate, most people
could not be protected in a
pandemic
5th August 2011
SEEK’s manufacturing approach
• A vaccine based on constant
peptides can be manufactured
in chemical plants
• Such a vaccine can be made
and administered in large
quantities, prior to a pandemic,
thereby protecting a large
proportion of the population
5th August 2011
SEEK’s antigen selection method
• The use of a proprietary
computer algorithm has allowed
the identification of these
constant peptides, making the
development of the vaccine
feasible
• This technology can also be
applied to the identification of
vaccines for other highly-mutating
viruses’
•SEEK has identified vaccine
candidates using this technology
against HIV, Hepatitis B & C,
Rotavirus A, mosquito-borne
diseases and others
5th August 2011