The current SARS-CoV-2 pandemic has increased not only the number of vaccines but also the number of adjuvants. Nevertheless, little was previously known about how adjuvants work.
For their research, the PEI science team isolated dendritic cells from donor blood, cells that belong to both the innate and acquired immune systems. They compared aluminum hydroxide, which is commonly used as an adjuvant, as well as those that bind to Toll-like receptors. Toll-like receptors (TLR) are located on the plasma membrane of monocytes, natural killer cells, mast cells, or dendritic cells. They have an important function in innate immune defense, many binding e.g. bacterial or viral proteins. 10 different TLRs are known in humans.* Adjuvants can bind to the receptor and influence both nonspecific and specific immune responses.
The researchers developed two model systems: one with dendritic cells, and one in the form of a coculture of dendritic cells and lymphocytes (white blood cells: B, T, and NK cells). They tested 10 different adjuvants and established efficacy profiles.
The TLR7/8 agonist resiquimod was found to be particularly useful for antiviral immune response.
Original publication:
Rossmann, L., Bagola, K., Stephen, T., Gerards, A.L., Walber, B., Ullrich, A., Schülke, S., Kamp, C., Spreitzer, I., Hasan, M., David-Watine, B., Shorte, S., Bastian, M., van Zandbergen, G. (2021): Distinct single component adjuvants steer 1 human DC-mediated T cell polarization via Toll-like receptor signaling toward a potent antiviral immune response. Proc Natl Acad Sci U S A 118: e2103651118.
Sources:
* About Toll-like receptors:
Siegmund-Schultze, N. (2007). Toll-like receptors: New target structure for immunostimulatory drugs. Dtsch Arztebl 2007; 104(16): A-1072 / B-954 / C-908. https://www.aerzteblatt.de/archiv/55316/Toll-like-Rezeptoren-Neue-Zielstruktur-fuer-immunstimulierende-Medikamente