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学科主题: 实验动物
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PEG as a spacer arm markedly increases the immunogenicity of meningococcal group Y polysaccharide conjugate vaccine
作者: 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
发表日期: 2013-11-28
DOI: 10.1016/j.jconrel.2013.03.008
卷: 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
所属项目编号: 20906095
项目资助者: Natural Science Foundation of China ; Hundred Talents Program of the Chinese Academy of Sciences
WOS记录号: WOS:000327601200043
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内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/54091
Appears in Collections:实验动物科学部_期刊论文

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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

Recommended Citation:
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.
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