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PEG as a spacer arm markedly increases the immunogenicity of meningococcal group Y polysaccharide conjugate vaccine
Huang, Qingrui1,4; Li, Dongxia1; Kang, Aijun3; An, Wenqi2; Fan, Bei2; Ma, Xiaowei2; Ma, Guanghui1; Su, Zhiguo1; Hu, Tao1
关键词Neisseria Meningitidis Conjugate Vaccine Spacer Arm Polyethylene Glycol Immunogenicity
刊名JOURNAL OF CONTROLLED RELEASE
2013-11-28
DOI10.1016/j.jconrel.2013.03.008
172期:1页:382-389
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Chemistry, Multidisciplinary ; Pharmacology & Pharmacy
研究领域[WOS]Chemistry ; Pharmacology & Pharmacy
关键词[WOS]PEGYLATED HEMOGLOBIN ; IN-VIVO ; DISEASE ; STAPHYLOKINASE ; THIOLATION ; ANTIBODIES ; TOLERANCE ; ANTIGEN ; SAFETY
英文摘要

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. (C) 2013 Elsevier B. V. All rights reserved.

语种英语
WOS记录号WOS:000327601200043
项目编号20906095
资助机构Natural Science Foundation of China ; Hundred Talents Program of the Chinese Academy of Sciences
引用统计
被引频次:15[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/54091
专题实验动物科学部
北京大学医学部管理机构_医学部
作者单位1.Hualan Biol Engn Inc, Xinxiang 453003, Henan Province, Peoples R China
2.Chinese Acad Sci, Inst Proc Engn, Natl Key Lab Biochem Engn, Beijing 100190, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Dept Lab Anim Sci, Beijing 100191, Peoples R China
4.Univ Chinese Acad Sci, Beijing 100190, Peoples R China
推荐引用方式
GB/T 7714
Huang, Qingrui,Li, Dongxia,Kang, Aijun,et al. PEG as a spacer arm markedly increases the immunogenicity of meningococcal group Y polysaccharide conjugate vaccine[J]. JOURNAL OF CONTROLLED RELEASE,2013,172(1):382-389.
APA Huang, Qingrui.,Li, Dongxia.,Kang, Aijun.,An, Wenqi.,Fan, Bei.,...&Hu, Tao.(2013).PEG as a spacer arm markedly increases the immunogenicity of meningococcal group Y polysaccharide conjugate vaccine.JOURNAL OF CONTROLLED RELEASE,172(1),382-389.
MLA Huang, Qingrui,et al."PEG as a spacer arm markedly increases the immunogenicity of meningococcal group Y polysaccharide conjugate vaccine".JOURNAL OF CONTROLLED RELEASE 172.1(2013):382-389.
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