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So we talked about the first generation
vaccine adjuvants, which tended
to be particulate carriers.
Now I'd like to introduce
the second generation.
The second generation are often
called immune potentiators,
because essentially what they are
are bits and pieces, components,
or whole cells, even,
of bacteria and viruses,
which activate innate immunity.
And this slide starts to give
some background on the kind
of recognition systems
available to recognize
these immune potentiators.
So the most well-identified receptor
system are the toll-like receptors.
So toll-like receptors
are present sometimes
on the exterior cell
membrane, sometimes
on endosomal compartments.
And the toll-like receptors
are able to recognize
essentially full bacteria and
viruses or components thereof.
And bits and pieces of
bacteria and viruses
have been used as adjuvants
for quite some time,
but it was really
only in the mid-1990s
that the toll-like receptors
were first identified.
And then it became
more clear exactly
how these adjuvants worked, because
they were triggering these TLRs.
And so there are at least
TLRs identified in man,
and potentially all
of them can be targets
for new generation
vaccine adjuvants,
which we call immune potentiators.
And certainly, the TLRs are not
the only receptor system available.
Certainly NOD, CLR, RIG-I,
STING agonists are emerging.
But as I'll highlight
in later slides,
TLR agonists are the
most advanced and are
even included in licensed products.
And you see here a separation
of some extracellular
TLRs like TLR 4, 1, 2, 5, and 6.
And there are some intracellular
endosomal TLRs, 7, 8, 9, and 3.
But essentially, they mostly
converge on similar signaling pathways
through NYD88 or TRIF and end
up with triggering transduction
pathways for cytokines,
which tend to trigger
the kind of innate
activation necessary to make
a vaccine adjuvant effective.
