Moderate PEGylation of the carrier protein improves the polysaccharide-specific immunogenicity of meningococcal group A polysaccharide conjugate vaccine
Moderate PEGylation of the carrier protein improves the polysaccharide-specific immunogenicity of meningococcal group A polysaccharide conjugate vaccine
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载体蛋白的适度聚乙二醇化提高了A群脑膜炎球菌多糖结合疫苗的多糖特异性免疫原性
DOI：
10.1016/j.vaccine.2015.04.094
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发表时间：
2015
期刊：
影响因子：
5.5
通讯作者：
Hu Tao
中科院分区：
文献类型：
--
作者：
Zhang Tingting;Yu Weili;Wang Yanfei;Hu Tao
脑膜炎奈瑟菌可引起严重的暴发性疾病，如脑膜炎。脑膜炎球菌荚膜多糖（PS）是一种不能诱导免疫记忆的关键毒力决定因子。将PS与载体蛋白偶联，可显著提高PS的免疫原性，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，在游离载体蛋白与缀合物疫苗共同施用后，针对载体蛋白的强免疫应答可抑制针对PS的免疫应答。然而，尚不清楚抑制或增强蛋白特异性免疫原性是否可以提高缀合物疫苗的PS特异性免疫原性。因此，中度聚乙二醇化、广泛聚乙二醇化和寡聚化用于调节缀合物疫苗（PS-TT）中破伤风类毒素（TT）的免疫原性。中度PEG化导致PS-TT引起的PS特异性IgG滴度增加2.7倍。相比之下，TT的广泛PEG化和寡聚化分别导致PS-TT引起的PS特异性IgG滴度降低1.4倍和1.6倍。适度的PEG化修饰可以通过轻度抑制TT特异性免疫原性来增加PS-TT的PS特异性免疫原性。PS-TT的特异性免疫原性通过显著抑制或增强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，提高脑膜炎球菌PS结合疫苗的PS特异性免疫原性。
Neisseria meningitidiscan 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-TT. 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.