Abstract
mBio 2017; 8: e00492-17
This highly important and interesting article presents the development and application of bacterial enzymatic combinatorial chemistry (BECC), by which novel compounds could be obtained that have the potential to be used as adjuvants in future vaccines.
The desire for a next generation of vaccines against various infectious diseases appears to be unbroken. Such vaccines also need a next generation of adjuvants, specifically tailored and possessing a high potential to significantly increase the immunogenic response. Earlier identified adjuvants (like Freund’s adjuvant) that improve antigen immunogenicity and stability were obtained by trial-and-error experiments. Such adjuvants proved to be ideal, resulting in complement fixation and opsonization of pathogens, via Th2 responses. Still, it might be very helpful to stimulate instead a Th1 response, particularly via the TLR4 pathway applying significantly less toxic lipid A derivatives. Here, one well-known example is 3-O-deacyl-4’-monophosphoryl lipid A (MPLA), which has currently been licensed for application in two vaccines. However, both, the production of MPLA and of similar molecules by derivatization of isolated lipid A or even by chemical synthesis is complicated and costly. Thus, alternative ways are required to obtain novel and effective adjuvant molecules at rather low cost. One possible way is presented in this article, in which authors clearly prove BECC is an efficient tool to isolate various TLR4 ligands with adjuvant potential, based on lipid A structures and by removal/introduction of lipid A-modifying enzymes into lipid A biosynthesis of different Gram-negative bacteria. In addition, in vitro screening protocols are presented that identify such adjuvant compounds. This novel approach appears to be highly promising and will for sure impact future development of next-generation vaccines.
I thank Alan Cross for calling my attention to this article.