Synthetic vaccines targeting Mincle through conjugation of trehalose dibehenate

Abstract

The covalent fusion of immunostimulatory adjuvants to immunogenic antigens is a promising strategy for the development of effective synthetic vaccines for infectious diseases. Herein, we describe the conjugation of a...

A lipid nanoparticle platform incorporating trehalose glycolipid for exceptional mRNA vaccine safety

“…However, this raises intriguing questions about the underlying mechanisms that contribute to their immune efficacy compared to that of LNPs containing ionizable lipids. A previous study developed a synthetic vaccine targeting the Mincle receptor by conjugating TDB to protein carriers [ 17 , 18 ]. Mincle receptors on immune cells specifically recognize certain bacterial and fungal infections, making them promising targets for vaccine development.…”

“…As a simplified synthetic analog of TDM, 6,6′-trehalose dibehenate (TDB) has been used in liposomal subunit vaccines as an adjuvant acting as a Mincle ligand ( Fig. S1 ) [ 17 , 18 ]. Sulfolipids in the form of sulfate esters activate bacterial phagocytosis [ 19 ].…”

Chimeric NOD2 Mincle Agonists as Vaccine Adjuvants

“…Disappointingly, the conjugation of TDB to immunogenic Mycobacterium tuberculosis peptides (ESAT6 1−20 and TB10.4 3−11 ) resulted in a vaccine construct that failed to be effective. 29,30 This was surprising given that an ESAT6 1−20 / TB10.4 3−11 -Pam 2 Cys conjugate provided protection against M. tuberculosis in a murine vaccination study, 31 and that TDB, a synthetic derivative of the major cell wall component of M. tuberculosis, exhibits potent Mincle-mediated adjuvant activity. 32 Despite the challenge of conjugating Mincle ligands to other immunomodulatory agents to provide enhanced immunity, we reasoned that effective Mincle-NOD chimeric adjuvants could be developed.…”

“…Mincle is a promising new target for vaccine development. − NOD ligands have long been known for their adjuvanticity, , however, they can be toxic, thereby necessitating careful application or structural modifications. − The only Mincle-NOD conjugate prepared to date consists of trehalose dimycolate (TDM) conjugated to muramyl dipeptide (MDP) using a succinic acid linker, although the adjuvanticity of this compound was not demonstrated. Disappointingly, the conjugation of TDB to immunogenic Mycobacterium tuberculosis peptides (ESAT6 1–20 and TB10.4 3–11 ) resulted in a vaccine construct that failed to be effective. , This was surprising given that an ESAT6 1–20 /TB10.4 3–11 -Pam 2 Cys conjugate provided protection against M. tuberculosis in a murine vaccination study, and that TDB, a synthetic derivative of the major cell wall component of M.…”