title: Moderate PEGylation of the carrier protein improves the polysaccharide-specific immunogenicity of meningococcal group A polysaccharide conjugate vaccine.
abstract: Neisseria meningitidis can cause severe and fulminant diseases such as meningitis. Meningococcal capsular polysaccharide (PS) is a key virulence determinant that is not able to induce immunological memory. Conjugation of PS to a carrier protein can significantly increase the immunogenicity of PS and induce immunological memory. Due to the classically described carrier-induced epitopic suppression (CIES) mechanisms, a strong immune response against the carrier protein could suppress the immune response to PS after coadministration of free carrier protein with the conjugate vaccine. However, it was not clear whether suppressing or enhancing the protein-specific immunogenicity could improve the PS-specific immunogenicity of the conjugate vaccine. Thus, moderate PEGylation, extensive PEGylation and oligomerization were used to regulate the immunogenicity of tetanus toxoid (TT) in the conjugate vaccine (PS-TT). Moderate PEGylation led to a 2.7-fold increase in the PS-specific IgG titers elicited by PS-TT. In contrast, extensive PEGylation and oligomerization of TT led to 1.4-fold and 1.6-fold decrease in the PS-specific IgG titers elicited by PS-TT, respectively. The PS-specific immunogenicity of PS-TT can be increased by moderate PEGylation through mild suppression of the TT-specific immunogenicity. The PS-specific immunogenicity of PS-TT was decreased through significant suppression or enhancement of the TT-specific immunogenicity. Thus, our study contributes to understand the CIES mechanisms and improve the PS-specific immunogenicity of a meningococcal PS conjugate vaccine.
authors.affiliation: School of Chemistry and Chemical Engineering, University of South China, Hengyang 421001, Hunan Province, China; National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China.
authors.forename: Weili
authors.initials: W
authors.lastname: Yu
authors.affiliation: School of Chemistry and Chemical Engineering, University of South China, Hengyang 421001, Hunan Province, China.
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China. Electronic address: thu@ipe.ac.cn.
authors.forename: Tao
authors.initials: T
authors.lastname: Hu
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood* / Q000276:immunology; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D022401:Meningococcal Vaccines / Q000737:chemistry* / Q000276:immunology*; D008807:Mice, Inbred BALB C; D009345:Neisseria meningitidis / Q000276:immunology; D011092:Polyethylene Glycols / Q000737:chemistry*; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D013745:Tetanus Toxoid / Q000737:chemistry* / Q000276:immunology; D018074:Vaccines, Conjugate / Q000737:chemistry / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D022401:Meningococcal Vaccines; D011135:Polysaccharides, Bacterial; D013745:Tetanus Toxoid; D018074:Vaccines, Conjugate; C043226:meningococcal group A polysaccharide; D011092:Polyethylene Glycols
keywords: Conjugate vaccine; Meningococcal polysaccharide; Oligomerization; PEGylation