Peptide adjacent to glycosylation sites impacts immunogenicity of glycoconjugate vaccine

// Zhongrui Ma 1,2 , Huajie Zhang 1 , Peng George Wang 1,2 , Xian-Wei Liu 1 and Min Chen 1 1 The State Key Laboratory of Microbial Technology, National Glycoengineering Research Center, School of Life Sciences, Shandong University, Jinan, Shandong, China 2 Department of Chemistry, Georgia State University, Atlanta, Georgia, United States Correspondence to: Min Chen, email: // Xian-Wei Liu, email: // Keywords : glycoconjugate vaccine, E. coli N-glycosylation system, glycosylation site, immunogenicity, glycopeptide, Immunology Received : May 10, 2017 Accepted : June 19, 2017 Published : August 04, 2017 Abstract Glycoconjugate vaccine is composed of polysaccharides (PSs) covalently linked with carrier protein. Glycosylation site selection, as a significant factor leading to heterogeneities of glycoconjugate structure, draws more and more attentions for its impact on the immunogenicity of glycoconjugate vaccine. To elucidate the relationship between glycosylation connectivity and immunogenicity of glycoconjugate vaccine, in this study, anti- E. coli O157:H7 glycoconjugate O-PS-MBP with defined connectivity, and three selected peptide segments GS1, GS2, GS3 derived from O-PS-MBP was synthesized. Immunogenicity results showed that only peptides adjacent to the glycosylation sites (GS1 and GS2) promoted the generation of PS-specific IgG antibodies and contributed to PS-specific IgG subclass distribution. Furthermore, GS1 and GS2 had significant priming effect for eliciting PS-specific IgG antibodies. These results indicated that different locations of glycosylation sites could lead to diverse presentation of peptides and glycopeptides to APCs and influence the immunogenicity of glycoconjugate vaccine, which extend the current understanding of mechanism for adaptive immune system activation by glycoconjugate vaccine, and have implications for rational glycoconjugate vaccine design.