Preparation of glyco-gold nanoparticles carrying synthetic mycobacterial hexaarabinofuranoside and their evaluation in vivo

Abstract

Some bacterial glycans are specific markers for detection and serological identification of microorganisms and are widely used as antigenic components of vaccines. The use of gold nanoparticles as carriers for glyco-epitopes is becoming an important alternative to the traditional conjugation with proteins and synthetic polymers. In this study, we aimed at preparation and evaluation in vivo of glyco-gold nanoparticles (glyco-GNPs) bearing the terminal branched hexaarabinofuranoside fragment (Ara6) of arabinan domains of lipoarabinomannan and arabinogalactan, which are principal polysaccharides of the cell wall of Mycobacterium tuberculosis, the causative agent of tuberculosis. Specifically, we were interested in checking if the antibodies generated against Ara6-GNPs would recognize the natural saccharides on the cell surface of different mycobacterial strains. Two synthetic Ara6 glycosides with amino-functionalized spacer aglycons differing in length and hydrophilicity were directly conjugated with spherical gold nanoparticles (d = 15 nm) to give two sets of glyco-GNPs which were used for immunization of rabbits. Dot assay revealed cross-reactions for the two obtained antisera with the hexaarabinofuranoside with 2-aminoethyl aglycon used for the preparation of glyco-GNPs. Both antisera contained high titers of antibodies specific for Mycobacteria as shown by enzyme-linked immunosorbent assay using M. bovis and M. smegmatis cells as antigens while gave a weak response with M. phlei cells and no interaction with E. coli cells. The results obtained suggest that glyco-GNPs are promising agents for generation of anti-mycobacterial antibodies.

Gold nanoparticles for preparation of antibodies and vaccines against infectious diseases

“…For immunoassay of mycobacteria, GNPs were conjugated to the penta-and hexasaccharide fragments of mycobacterial lipoarabinomannan by using aglycon spacers of various lengths [130]. Rabbit polyclonal antibodies to these conjugates were developed.…”

“…Subsequently, it was shown that vaccination of pregnant mice with gold glyconanoparticles carrying L. monocytogenes peptides protects Figure 4. Schematic illustration of modulation of antibacterial immunity with bacterial-membrane-coated nanoparticles [130].…”