以乙型肝炎核心抗原病毒样颗粒作为新型载体蛋白的脑膜炎球菌多糖结合疫苗的研制，可诱导产生持久而强烈的细胞免疫应答。
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.
机构信息
Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China; State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China.
State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, PR China.
出版信息
Vaccine. 2019 Feb 8;37(7):956-964. doi: 10.1016/j.vaccine.2018.12.073. Epub 2019 Jan 14.
Neisseria 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-P10k-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.
脑膜炎奈瑟菌引起的脑膜炎是一种危及生命的急性感染，死亡率和严重后遗症发生率均较高。脑膜炎球菌荚膜多糖可用于预防脑膜炎球菌病；然而，研究发现将多糖与载体蛋白结合可以提高其免疫原性，并在婴儿和幼儿中诱导记忆反应。然而，由于载体蛋白数量有限，重复给予糖缀合物疫苗可能导致载体诱导的表位抑制。在这项研究中，全长乙型肝炎核心抗原病毒样颗粒（HBc VLPs）被用作新型潜在载体蛋白，用于将脑膜炎奈瑟菌 C 群多糖（CPS）与不同长度（2、5 和 10 kDa）的杂双功能聚乙二醇（PEG）连接子缀合。对 CPS-PEG-HBc 缀合物疫苗的理化性质进行了全面表征。TEM、DLS、天然琼脂糖凝胶电泳和 HPLC 分析均证实了缀合的成功。与普通 CPS 和 CPS 与 HBc 的物理混合物相比，用缀合物疫苗免疫可使 CPS 特异性 IgG 滴度增加约 10 倍，并具有显著的增强作用。HBc 缀合诱导了 Th1 细胞免疫类型反应的转变，这可通过增加 IgG2a 亚类的产生来评估。此外，缀合物疫苗的接种还引起了更高亲和力功能抗体和更持久的免疫记忆。在第 18 周时，CPS-P2k-HBc、CPS-P5k-HBc 和 CPS-P10k-HBc 引起的 IgG 滴度保持其峰值的 38.1%、17.9%和 33.3%。所有这些结果表明，HBc VLPs 可用作潜在载体蛋白来开发有效诱导长期和强烈细胞免疫反应的多糖缀合物疫苗。
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