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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
2013-11-28
Source PublicationJOURNAL OF CONTROLLED RELEASE
Volume172Issue:1Pages:382-389
AbstractNeisseria 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.
KeywordNeisseria Meningitidis Conjugate Vaccine Spacer Arm Polyethylene Glycol Immunogenicity
SubtypeArticle
WOS HeadingsScience & Technology ; Physical Sciences ; Life Sciences & Biomedicine
Indexed BySCI
Language英语
WOS KeywordPEGYLATED HEMOGLOBIN ; IN-VIVO ; DISEASE ; STAPHYLOKINASE ; THIOLATION ; ANTIBODIES ; TOLERANCE ; ANTIGEN ; SAFETY
WOS Research AreaChemistry ; Pharmacology & Pharmacy
WOS SubjectChemistry, Multidisciplinary ; Pharmacology & Pharmacy
WOS IDWOS:000327601200043
Citation statistics
Cited Times:21[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.ipe.ac.cn/handle/122111/13662
Collection研究所(批量导入)
Affiliation1.Chinese Acad Sci, Inst Proc Engn, Natl Key Lab Biochem Engn, Beijing 100190, Peoples R China
2.Hualan Biol Engn Inc, Xinxiang 453003, Henan Province, 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
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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