Zhang Tingting, Yu Weili, Wang Yanfei, Hu Tao
School of Chemistry and Chemical Engineering, University of South China, Hengyang 421001, Hunan Province, China; National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China.
National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China.
Vaccine. 2015 Jun 22;33(28):3208-14. doi: 10.1016/j.vaccine.2015.04.094. Epub 2015 May 8.
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-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.
脑膜炎奈瑟菌可引起严重且暴发性的疾病，如脑膜炎。脑膜炎球菌荚膜多糖（PS）是一种关键的毒力决定因素，无法诱导免疫记忆。将PS与载体蛋白结合可显著提高PS的免疫原性并诱导免疫记忆。由于经典描述的载体诱导表位抑制（CIES）机制，在将游离载体蛋白与结合疫苗共同给药后，针对载体蛋白的强烈免疫反应可能会抑制对PS的免疫反应。然而，尚不清楚抑制或增强蛋白特异性免疫原性是否能提高结合疫苗的PS特异性免疫原性。因此，采用适度聚乙二醇化、广泛聚乙二醇化和寡聚化来调节结合疫苗（PS-TT）中破伤风类毒素（TT）的免疫原性。适度聚乙二醇化使PS-TT诱导的PS特异性IgG滴度增加了2.7倍。相比之下，TT的广泛聚乙二醇化和寡聚化分别使PS-TT诱导的PS特异性IgG滴度降低了1.4倍和1.6倍。通过适度抑制TT特异性免疫原性，适度聚乙二醇化可提高PS-TT的PS特异性免疫原性。通过显著抑制或增强TT特异性免疫原性，PS-TT的PS特异性免疫原性会降低。因此，我们的研究有助于理解CIES机制并提高脑膜炎球菌PS结合疫苗的PS特异性免疫原性。
