title: PEG as a spacer arm markedly increases the immunogenicity of meningococcal group Y polysaccharide conjugate vaccine.
abstract: Neisseria meningitidis is a life-threatening pathogen that causes meningitis and other clinical manifestations. As a key virulence determinant, meningococcal capsular polysaccharide (PS) can be used to prevent meningococcal diseases. Conjugation of PS to carrier protein can significantly improve the immunogenicity of PS and induce memory response in infants and young children. However, the conjugate vaccine may suffer from steric shielding of antigenic PS epitopes by carrier protein. Here, a heterobifunctional polyethylene glycol (PEG) was used as a spacer arm to conjugate meningococcal group Y capsular PS with tetanus toxoid (TT). PEG can avoid self-crosslink of PS and increase the PS/TT ratio of the vaccine. Significant structural change in TT and PS was not observed upon conjugation. As compared to the vaccine without PEG, immunization with the vaccine using PEG as the spacer arm led to a 3.0-fold increase in the PS-specific IgG titers and a prolonged immune persistence. Paradoxically, PEG, a non-immunogenic hydrophilic polymer has been widely used to couple therapeutic protein for increasing its circulatory time and decreasing its immunogenicity. Presumably, PEG can fully decrease the steric shielding effect of TT on antigenic epitopes of PS and suppress the immunogenicity of TT. In addition, PEG can prolong the immune persistence of the conjugate vaccine and improve its ability to elicit cellular immunity. Thus, PEG can be used as a spacer arm to develop more effective PS conjugate vaccine for prevention of bacterial infection.
authors.affiliation: National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100190, China.
authors.forename: Qingrui
authors.initials: Q
authors.lastname: Huang
authors.affiliation: National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China.
authors.forename: Dongxia
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Laboratory Animal Science, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Aijun
authors.initials: A
authors.lastname: Kang
authors.affiliation: Hualan Biological Engineering, Inc., Xinxiang 453003, Henan Province, China.
authors.forename: Wenqi
authors.initials: W
authors.lastname: An
authors.affiliation: Hualan Biological Engineering, Inc., Xinxiang 453003, Henan Province, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Fan
authors.affiliation: Hualan Biological Engineering, Inc., Xinxiang 453003, Henan Province, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Ma
authors.affiliation: National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China.
authors.forename: Guanghui
authors.initials: G
authors.lastname: Ma
authors.affiliation: National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Su
authors.affiliation: National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China. Electronic address: thu@home.ipe.ac.cn.
authors.forename: Tao
authors.initials: T
authors.lastname: Hu
mesh_terms: D000818:Animals; D000915:Antibody Affinity; D005260:Female; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008585:Meningitis, Meningococcal / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D009345:Neisseria meningitidis / Q000276:immunology*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D011135:Polysaccharides, Bacterial / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*
chemical_list: D007074:Immunoglobulin G; D011135:Polysaccharides, Bacterial; D018074:Vaccines, Conjugate; D011092:Polyethylene Glycols
keywords: Conjugate vaccine; Immunogenicity; Neisseria meningitidis; Polyethylene glycol; Spacer arm