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Moderate PEGylation of the carrier protein improves the polysaccharide-specific immunogenicity of meningococcal group A polysaccharide conjugate vaccine

机译:载体蛋白的适度PEG化可改善A型脑膜炎球菌多糖结合疫苗的多糖特异性免疫原性

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Neisseria meningitidis can cause severe and fulminant diseases such as meningitis. Meningococcal capsular polysaccharide (PS) is a key virulence determinant that is not able to induce immunological memory. Conjugation of PS to a carrier protein can significantly increase the immunogenicity of PS and induce immunological memory. Due to the classically described carrier-induced epitopic suppression (CIES) mechanisms, a strong immune response against the carrier protein could suppress the immune response to PS after coadministration of free carrier protein with the conjugate vaccine. However, it was not clear whether suppressing Or enhancing the protein-specific immunogenicity could improve the PS-specific immunogenicity of the conjugate vaccine. Thus, moderate PEGylation, extensive PEGylation and oligomerization were used to regulate the immunogenicity of tetanus toxoid (TT) in the conjugate vaccine (PS-TT). Moderate PEGylation led to a 2.7-fold increase in the PS-specific IgG titers elicited by PS-IT. In contrast, extensive PEGylation and oligomerization of TT led to 1.4-fold and 1.6-fold decrease in the PS-specific IgG titers elicited by PS-TT, respectively. The PS-specific immunogenicity of PS-TT can be increased by moderate PEGylation through mild suppression of the TT-specific immunogenicity. The PS-specific immunogenicity of PS-TT was decreased through significant suppression or enhancement of the TT-specific immunogenicity. Thus, our study contributes to understand the CIES mechanisms and improve the PS-specific immunogenicity of a meningococcal PS conjugate vaccine. (C) 2015 Elsevier Ltd. All rights reserved.
机译:脑膜炎奈瑟氏球菌可引起严重和暴发性疾病,例如脑膜炎。脑膜炎球菌荚膜多糖(PS)是不能诱导免疫记忆的关键毒力决定因素。 PS与载体蛋白的缀合可以显着增加PS的免疫原性并诱导免疫记忆。由于经典描述的载体诱导的表位抑制(CIES)机制,在结合载体疫苗与游离载体蛋白并用后,针对载体蛋白的强免疫反应可以抑制对PS的免疫反应。但是,尚不清楚抑制或增强蛋白质特异性免疫原性是否能改善结合疫苗的PS特异性免疫原性。因此,适度的PEG化,广泛的PEG化和低聚被用于调节结合疫苗(PS-TT)中的破伤风类毒素(TT)的免疫原性。中等的PEG化会使PS-IT引起的PS特异性IgG滴度增加2.7倍。相反,TT的广泛PEG化和低聚分别导致PS-TT引起的PS特异性IgG效价分别降低1.4倍和1.6倍。 PS-TT的PS特异性免疫原性可通过适度地抑制TT特异性免疫原性而通过适度的PEG化来提高。 PS-TT的PS特异性免疫原性通过显着抑制或增强TT特异性免疫原性而降低。因此,我们的研究有助于了解CIES机制和改善脑膜炎球菌PS结合疫苗的PS特异性免疫原性。 (C)2015 Elsevier Ltd.保留所有权利。

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