Design and synthesis of multivalent α-1,2-trimannose-linked bioerodible microparticles for applications in immune response studies of Leishmania major infection

Abstract

Leishmaniasis, a neglected tropical disease, currently infects approximately 12 million people worldwide with 1 to 2 million new cases each year in predominately underdeveloped countries. The treatment of the disease is severely underdeveloped due to the ability of the Leishmania pathogen to evade and abate immune responses. In an effort to develop anti-leishmaniasis vaccines and adjuvants, novel carbohydrate-based probes were made to study the mechanisms of immune modulation. In this study, a new bioerodible polyanhydride microparticle was designed and conjugated with a glycodendrimer molecular probe. This molecular probe incorporates a pathogen-like multivalent display of α-1,2-trimannose, for which a more efficient synthesis was designed, with a tethered fluorophore. Further attachment of the glycodendrimer to a biocompatible, surface eroding microparticle allows for targeted uptake and internalization of the pathogen-associated oligosaccharide by phagocytic immune cells. The α-1,2-trimannose-linked bioerodible microparticles were found to be safe after administration into the footpad of mice and demonstrated a similar response to α-1,2-trimannose-coated latex beads during L. major footpad infection. Furthermore, the bioerodible microparticles allowed for investigation of the role of pathogen-associated oligosaccharides for recognition by pathogen-recognition receptors during L. major-induced leishmaniasis.

Applications of Nanovaccines for Disease Prevention in Cattle

“…Multiple functionalization techniques are available based on the size and type of ligand. Polymeric particles have been functionalized with dimannose to target CLRs and TLRs (Tamayo et al, 2010;Carrillo-Conde et al, 2011;Chavez-Santoscoy et al, 2012;Vela Ramirez et al, 2014;Phanse et al, 2017;Rintelmann et al, 2019). These particles successfully activated DCs and CD8+ T cells while up-regulating MHC II and pro-inflammatory cytokines (Tamayo et al, 2010;Carrillo-Conde et al, 2011;Vela Ramirez et al, 2014;Phanse et al, 2017).…”