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佐剂组合物对含来自脑膜炎奈瑟菌1类孔蛋白保护性表位的多抗原肽(MAP)免疫应答的影响

Effect of adjuvant composition on immune response to a multiple antigen peptide (MAP) containing a protective epitope from Neisseria meningitidis class 1 porin.

作者信息

Christodoulides M, Rattue E, Heckels J E

机构信息

Molecular Microbiology Group, University of Southampton Medical School, Southampton General Hospital, UK.

出版信息

Vaccine. 1999 Aug 20;18(1-2):131-9. doi: 10.1016/s0264-410x(99)00190-5.

Abstract

A variety of adjuvants with the potential for use with experimental human vaccines were used for immunisation of mice, in an attempt to augment the humoral immune response to a multiple antigen peptide (MAP) containing a protective epitope from the sero-subtype specific class 1 porin protein of Neisseria meningitidis, in tandem with a Th-cell epitope. Surface plasmon resonance showed that combinations of the immunomodulators pluronic block co-polymer, muramyl dipeptide and monophosphoryl lipid A (MPL), increased the magnitude and avidity of the immune response in comparison with both Al(OH)3 and Freund-type adjuvants. In addition, the incorporation of MPL was essential for the induction of a broad distribution of antibody isotypes. The antibodies induced recognised the native protein in meningococcal outer membranes in a subtype-specific manner. The formulations containing these multiple immunomodulators which have already been used in human phase I/II trials with experimental vaccines, are candidates for inclusion in future human vaccines based on synthetic peptides containing defined, protective epitopes.

摘要

为增强对包含来自脑膜炎奈瑟菌血清亚型特异性1类孔蛋白保护性表位及Th细胞表位的多抗原肽(MAP)的体液免疫应答,多种有潜力用于人体实验性疫苗的佐剂被用于小鼠免疫。表面等离子体共振显示,与氢氧化铝和弗氏佐剂相比,免疫调节剂普朗尼克嵌段共聚物、胞壁酰二肽和单磷酰脂质A(MPL)的组合增加了免疫应答的强度和亲和力。此外,MPL的加入对于诱导广泛分布的抗体亚型至关重要。诱导产生的抗体以亚型特异性方式识别脑膜炎球菌外膜中的天然蛋白。这些含有多种免疫调节剂的制剂已用于人体I/II期实验性疫苗试验,有望纳入未来基于含特定保护性表位合成肽的人体疫苗。

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