A Synthetic Disaccharide Analogue from Neisseria meningitidis A Capsular Polysaccharide Stimulates Immune Cell Responses and Induces Immunoglobulin G (IgG) Production in Mice When Protein-Conjugated

Abstract

Some new phosphonoester-linked oligomers, stabilized analogues of the corresponding phosphate-bridged oligomers of Neisseria meningitidis A (MenA) capsular polysaccharide (CPS), were conjugated to human serum albumin (HSA), as a protein carrier model, and studied for immunological activities. We determined (i) in vitro, their biocompatibility (CAM test) and activity in inducing both T cell proliferation (CFSE method) and IL-2 release (ELISA), and (ii) in vivo, their ability to stimulate specific IgG antibody production (ELISA). All HSA-conjugated compounds induce T cell proliferation (40% of proliferation at 10(2) μM), whereas only the phosphonodisaccharide was effective (28% of proliferation at 10(2) μM) among the unconjugated forms. IL-2 release confirmed these results. In addition, the HSA-conjugated showed in vivo the capacity of eliciting the production of specific IgG antibodies. In conclusion, we obtained novel biocompatible, water-stable, and immunoactive MenA CPS analogues. A short disaccharide fragment showed the unusual behavior of triggering T cell proliferation in vitro.

Structure of a protective epitope reveals the importance of acetylation of Neisseria meningitidis serogroup A capsular polysaccharide

“…Over the past decades, several examples of glycan structural epitopes resolved at atomic resolution by X-crystallography have been reported, including Salmonella typhimurium lipopolysaccharide (10), Vibrio cholerae O1 (11), Shigella flexneri serotype 2a O-antigen (12), Mycobacterium tuberculosis PS (13), and group B Streptococcus PS (14). Understanding the structural basis of antigen-antibody binding events offers the promise for a guided rational design of innovative synthetic vaccines (15,16), and glycomimetics (17,18).…”

A stabilized glycomimetic conjugate vaccine inducing protective antibodies against Neisseria meningitidis serogroup A

“…We and others have explored the stabilization of the CPS in different ways. MenA CPS analogs in which the anomeric oxygen of the interglycosidic phosphodiester bond is replaced with a methylene group to obtain nonhydrolysable C-phosphono analogs of MenA CPS oligomers have been reported and mimics, in which the ring-oxygen is replaced by a methylene group, have also been conceived 30,31 . We previously generated short oligomers of these carbaMenA analogs, containing up to three repeating units ( Fig.…”

Recent Advances in the Synthesis of Glycoconjugates for Vaccine Development

“…However, only nanoparticles 220 , exposing a phosphonodisaccharide-functionalized monolayer, induced T cells proliferation and the increase of released interleukin-2 levels, the latter being a typical marker of T cell activation. Recently, HSA conjugates 209b , 211b and 213b [ 189 ] were shown to induce both T cell proliferation and interleukin-2 release in vitro, and to stimulate moderate specific IgG antibody production in vivo. All HSA-conjugated compounds 209b , 211b and 213b induced T cell proliferation (40% of proliferation at 102 μM), whereas only phosphonodisaccharide 211a was effective (28% of proliferation at 102 μM) among the unconjugated forms, showing the unusual behavior of triggering T cell proliferation in vitro and causing interleukin-2 release.…”