Synthetic mycobacterial molecular patterns work synergistically to recapitulate complete Freund’s adjuvant

Jean-Yves Dubé, Fiona McIntosh, Juan G. Zarruk, Samuel David, Jérôme Nigou, Marcel A. Behr

Jul 24, 2019
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Received Date: 3rd July 19

Complete Freund’s adjuvant (CFA) has historically been one of the most useful tools of immunologists.  Essentially comprised of dead mycobacteria and mineral oil, we asked ourselves what is special about the mycobacterial part of this adjuvant, and could it be recapitulated synthetically?  Here, we demonstrate the essentiality of N-glycolylated peptidoglycan plus trehalose dimycolate (both unique in mycobacteria) for the complete adjuvant effect using knockouts and chemical complementation.  A combination of synthetic N-glycolyl muramyl dipeptide and minimal trehalose dimycolate motif GlcC14C18 was able to induce experimental autoimmunity qualitatively similar to the whole mycobacteria in CFA.  This research outlines how to replace CFA with a consistent, molecularly defined adjuvant which may inform the design of immunotherapeutic agents and vaccines benefitting from cell-mediated immunity.  We also anticipate using synthetic microbe-associated molecular patterns (MAMPs) to study mycobacterial immunity and immunopathogenesis.

Read in full at bioRxiv.

This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

Nature Communications

Nature Research, Springer Nature