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用布鲁氏菌流产种铜锌超氧化物歧化酶合成肽疫苗接种的Balb/c小鼠免疫反应的调节

Modulation of immune responses in Balb/c mice vaccinated with Brucella abortus Cu-Zn superoxide dismutase synthetic peptide vaccine.

作者信息

Tabatabai L B, Pugh G W

机构信息

USDA, ARS, MWA, National Animal Disease Center, Ames, IA 50010.

出版信息

Vaccine. 1994 Aug;12(10):919-24. doi: 10.1016/0264-410x(94)90035-3.

Abstract

Three peptides, peptide 1 (GGDNYSDKPEPLGG), peptide 2 (LAEIKQRSLMVHGG) and peptide 3 (GGAPGEKDGKIVPAG), were synthesized based on the amino acid sequence of Brucella abortus Cu-Zn superoxide dismutase. These peptides were selected on the basis of their predicted hydrophilicity, flexibility and antigenicity profiles. The three peptides, singly or in combination, with or without the adjuvant monophosphoryl lipid A were administered to Balb/c mice as vaccines for brucellosis. The protective and immune responses induced by the peptide vaccines after challenge exposure to virulent B. abortus strain 2308 were compared to those obtained with salt-extractable proteins (BCSP) vaccine prepared from B. abortus strain 19, recombinant B. abortus Cu-Zn superoxide dismutase (rSOD) vaccine and non-vaccinated mice. Mice vaccinated with 30 micrograms of peptide 3 plus 50 micrograms monophosphoryl lipid A afforded two logs of protection (reduction in log10 colony-forming units compared with control mice) and one log of protection when given without monophosphoryl lipid A, whereas 5 micrograms of the salt-extractable proteins afforded three logs of protection. The rSOD and peptides 1 and 2 given with or without monophosphoryl lipid A afforded no protection. Superoxide dismutase-specific IgG antibody was present in postchallenge sera only if BCSP was present in the vaccine. Peptide-specific IgG antibodies were present in postchallenge sera of mice, and antibody concentrations were generally enhanced when monophosphoryl lipid A was included in the vaccine. The overall results with the peptide vaccines suggest that peptide 3 probably contains a specific sequence preferentially recognized by the cellular immune system leading to modulation of immune response mechanisms responsible for decreasing splenic infection.

摘要

基于流产布鲁氏菌铜锌超氧化物歧化酶的氨基酸序列合成了三种肽,即肽1(GGDNYSDKPEPLGG)、肽2(LAEIKQRSLMVHGG)和肽3(GGAPGEKDGKIVPAG)。这些肽是根据其预测的亲水性、柔韧性和抗原性图谱选择的。将这三种肽单独或组合使用,添加或不添加佐剂单磷酰脂质A,作为布鲁氏菌病疫苗接种给Balb/c小鼠。将肽疫苗在攻击暴露于强毒流产布鲁氏菌2308菌株后诱导的保护和免疫反应与用流产布鲁氏菌19菌株制备的盐可提取蛋白(BCSP)疫苗、重组流产布鲁氏菌铜锌超氧化物歧化酶(rSOD)疫苗以及未接种疫苗的小鼠所获得的反应进行比较。用30微克肽3加50微克单磷酰脂质A接种的小鼠提供了两个对数的保护(与对照小鼠相比,log10集落形成单位减少),在不添加单磷酰脂质A时提供了一个对数的保护,而5微克盐可提取蛋白提供了三个对数的保护。添加或不添加单磷酰脂质A的rSOD以及肽1和肽2均未提供保护。仅当疫苗中存在BCSP时,攻击后血清中才存在超氧化物歧化酶特异性IgG抗体。小鼠攻击后血清中存在肽特异性IgG抗体,并且当疫苗中包含单磷酰脂质A时,抗体浓度通常会增加。肽疫苗的总体结果表明,肽3可能包含一个被细胞免疫系统优先识别的特定序列,从而导致负责减少脾脏感染的免疫反应机制的调节。

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