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Other Talks in the Series: Vaccines

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.