Automated Glycan Assembly of Porphyromonas gingivalis Lipopolysaccharide Epitopes for Vaccine Design

Porphyromonas gingivalis (P. gingivalis) is the major cause of chronic periodontitis and is associated with systemic diseases, such as rheumatoid arthritis. A better understanding of the interplay of the human immune system and P. gingivalis lipopolysaccharide (LPS) may result in novel treatment and prevention strategies. Twelve LPS fragments of P. gingivalis were synthesized using automated glycan assembly, with the help of remote benzoyl ester participation to introduce 1,2-cis-glycosidic linkages. Saliva and sera derived from periodontitis patients, treated periodontitis patients, and healthy patients were screened for IgG and IgA antibodies using glycan microarrays. A tetrasaccharide antigen, α-d-Galp-(1→6)-α-d-Glcp-(1→4)-α-l-Rhap-(1→3)-2-β-d-GalNAc was identified as a glycoconjugate vaccine lead against P. gingivalis and elicited strong glycan-specific IgG responses in mice, showing binding to P. gingivalis W50 and suggesting potential for both targeted protection and broader prevention of systemic diseases linked to periodontitis.