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Conjugation of beta-glucan markedly increase the immunogencity of meningococcal group Y polysaccharide conjugate vaccine

机译:β-葡聚糖的结合显着提高了脑膜炎球菌Y型多糖结合疫苗的免疫原性

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摘要

Meningococcal disease is a fatal illness of sudden onset caused by Neisseria meningitides. Meningococcal capsular polysaccharide (CPS) is a major virulence factor that generally does not induce immunological memory. Conjugation with a carrier protein can significantly increase the immunogenicity of CPS and induce immunological memory. However, it is highly desired to optimize the CPS-specific immunogenicity of the conjugate vaccine. Although adjuvant has been widely used to improve the immunogenicity of antigens, co-administration and conjugation of adjuvant with the conjugate vaccine has rarely been investigated. As a stimulator of humoral and cellular immunity, beta-glucan can activate macrophages and trigger intracellular processes to secrete cytokines initiating inflammatory reactions. In the present study, a conjugate vaccine (CPS-TT) was generated by conjugation of tetanus toxoid (TT) with meningococcal group Y CPS. CPS-TT was further conjugated with beta-glucan to generate CPS-TT-G. Immunization with CPS-TT-G led to an 8.2-fold increase in the CPS-specific IgG titers as compared with CPS-TT. Presumably, conjugation of beta-glucan ensured the two components to simultaneously reach the antigen presenting cells and stimulate the immune response. In contrast, co-administration of beta-glucan suppressed the CPS-specific immunogenicity of CPS-TT. Thus, conjugation of beta-glucan is an effective strategy to markedly improve the CPS-specific immunogenicity of the conjugate vaccine. (C) 2015 Elsevier Ltd. All rights reserved.
机译:脑膜炎球菌病是由脑膜炎奈瑟氏球菌引起的突然发作的致命疾病。脑膜炎球菌荚膜多糖(CPS)是主要的致病因子,通常不会诱导免疫记忆。与载体蛋白结合可以显着提高CPS的免疫原性并诱导免疫记忆。然而,非常需要优化结合疫苗的CPS特异性免疫原性。尽管佐剂已被广泛用于改善抗原的免疫原性,但很少研究佐剂与结合疫苗的共同给药和结合。作为体液和细胞免疫的刺激剂,β-葡聚糖可以激活巨噬细胞并触发细胞内过程以分泌细胞因子,从而引发炎症反应。在本研究中,通过将破伤风类毒素(TT)与脑膜炎球菌Y CPS组缀合,产生了结合疫苗(CPS-TT)。 CPS-TT进一步与β-葡聚糖缀合以产生CPS-TT-G。与CPS-TT相比,CPS-TT-G免疫导致CPS特异性IgG滴度增加了8.2倍。据推测,β-葡聚糖的缀合可确保这两个成分同时到达抗原呈递细胞并刺激免疫反应。相反,β-葡聚糖的共同给药抑制了CPS-TT的CPS特异性免疫原性。因此,β-葡聚糖的缀合是显着改善缀合物疫苗的CPS特异性免疫原性的有效策略。 (C)2015 Elsevier Ltd.保留所有权利。

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