Simplified scalable synthesis of a water-soluble toll-like receptor 2 agonistic lipopeptide adjuvant for use with protein-based viral vaccines.

ABSTRACT: Toll-like receptors (TLRs) form a key bridge between the innate and adaptive immune systems. The lipopeptide based TLR2 agonists such as Pam₂CSK₄ are promising vaccine adjuvants but drawbacks include its surfactant like nature and cumbersome synthesis. Although the TLR2 activity of Pam₂CS-OMe is commensurate with Pam₂CSK₄, its water solubility is much less, rendering it ineffective for clinical use. In the present investigation, we designed a synthesis pathway for a novel water-soluble TLR2-active analogue, Pam₂CS-DMAPA (13), which enhanced the immunogenicity of recombinant SARS-CoV2 and hepatitis B antigens in mice. Co-formulation of compound 13 with 2 % aluminium hydroxide gel led to a further significant improvement in va

SUBMITTER: Brar DS 

PROVIDER: S-EPMC11614683 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature