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Development of meningococcal polysaccharide conjugate vaccine that can elicit long-lasting and strong cellular immune response with hepatitis B core antigen virus-like particles as a novel carrier protein
Xu, Lingling1,2; Li, Zhengjun2,3; Su, Zhiguo2; Yang, Yanli2; Ma, Guanghui2; Yu, Rong1; Zhang, Songping2
2019-02-08
Source PublicationVACCINE
ISSN0264-410X
Volume37Issue:7Pages:956-964
AbstractNeisseria meningitidis caused meningitis is life-threatening acute infection with high fatality and high frequency of severe sequelae. Meningococcal capsular polysaccharides can be used to prevent meningococcal disease; while conjugating the polysaccharides to carrier protein was found necessary to improve the immunogenicity and induce memory responses in infants and young children. Nevertheless, repeated administration of glycoconjugate vaccines might lead to carrier-induced epitope suppression due to limited number of carrier proteins. Here in this study, full-length hepatitis B core antigen virus-like particles (HBc VLPs) was used as a novel potential carrier protein for conjugation of meningococcal group C polysaccharides (CPS) with heterobifunctional polyethylene glycol (PEG) of different length (2, 5 and 10 kDa) as linkers. The physiochemical properties of the CPS-PEG-HBc conjugate vaccines were fully characterized. The TEM, DLS, native agarose gel electrophoresis, and HPLC analyses all confirmed the successful conjugation. As compared to plain CPS and the physical mixture of CPS and HBc, the immunization with the conjugate vaccines can generate about 10 times increase in CPS specific IgG titers with a significant boosting effect. HBc conjugation induced a shift to a Th1 cellular immune type response, as assessed by the increased IgG2a subclass production. In addition, vaccination of the conjugate vaccines elicited much enhanced avidity functional antibody and long-lasting immunological memory. IgG titers elicited by CPS-P2k-HBc, CPS-P5k-HBc and CPS-PlOk-HBc at week 18 maintained 38.1%, 17.9% and 33.3% of their peak values. All these results demonstrated that HBc VLPs can be used as potential carrier protein to develop polysaccharide conjugate vaccines effective in eliciting long-lasting and strong cellular immune response. (C) 2019 Elsevier Ltd. All rights reserved.
KeywordNeisseria meningitidis Conjugate vaccine Hepatitis B core antigen Virus-like particles
DOI10.1016/j.vaccine.2018.12.073
Language英语
WOS KeywordTETANUS TOXOID-CONJUGATE ; QUANTITATIVE ESTIMATION ; IMMUNOGENICITY ; SEQUENCE ; EPITOPE
Funding ProjectNational Key R & D Program of China[2016YFD0500800] ; National Key R & D Program of China[2016YFD0500809] ; National Natural Sciences Foundation of China[21821005] ; National Natural Sciences Foundation of China[81773623] ; National Natural Sciences Foundation of China[21808226]
WOS Research AreaImmunology ; Research & Experimental Medicine
WOS SubjectImmunology ; Medicine, Research & Experimental
Funding OrganizationNational Key R & D Program of China ; National Natural Sciences Foundation of China
WOS IDWOS:000458342400009
PublisherELSEVIER SCI LTD
Citation statistics
Document Type期刊论文
Identifierhttp://ir.ipe.ac.cn/handle/122111/27946
Collection中国科学院过程工程研究所
Corresponding AuthorYu, Rong; Zhang, Songping
Affiliation1.Sichuan Univ, West China Sch Pharm, Key Lab Drug Targeting & Drug Delivery Syst, Minist Educ, Chengdu 610041, Sichuan, Peoples R China
2.Chinese Acad Sci, Inst Proc Engn, State Key Lab Biochem Engn, Beijing 100190, Peoples R China
3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
Recommended Citation
GB/T 7714
Xu, Lingling,Li, Zhengjun,Su, Zhiguo,et al. Development of meningococcal polysaccharide conjugate vaccine that can elicit long-lasting and strong cellular immune response with hepatitis B core antigen virus-like particles as a novel carrier protein[J]. VACCINE,2019,37(7):956-964.
APA Xu, Lingling.,Li, Zhengjun.,Su, Zhiguo.,Yang, Yanli.,Ma, Guanghui.,...&Zhang, Songping.(2019).Development of meningococcal polysaccharide conjugate vaccine that can elicit long-lasting and strong cellular immune response with hepatitis B core antigen virus-like particles as a novel carrier protein.VACCINE,37(7),956-964.
MLA Xu, Lingling,et al."Development of meningococcal polysaccharide conjugate vaccine that can elicit long-lasting and strong cellular immune response with hepatitis B core antigen virus-like particles as a novel carrier protein".VACCINE 37.7(2019):956-964.
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