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来自百日咳博德特氏菌的重组外膜蛋白Q和假定脂蛋白虽能诱导强烈的体液反应,但在小鼠肺部定植模型中单独使用时并无保护作用。

Recombinant outer membrane protein Q and putative lipoprotein from Bordetella pertussis inducing strong humoral response were not protective alone in the murine lung colonization model.

作者信息

Yilmaz Çiğdem, Özcengiz Erkan, Özcengiz Gülay

机构信息

Department of Biological Sciences, Middle East Technical University , Ankara , Turkey.

Pharmada Pharmaceuticals , Ankara , Turkey.

出版信息

Turk J Biol. 2018 Apr 27;42(2):123-131. doi: 10.3906/biy-1709-23. eCollection 2018.

Abstract

Despite high vaccination coverage after introduction of whole cell (wP) and acellular pertussis (aP) vaccines, pertussis resurgence has been reported in many countries. aP vaccines are commonly preferred due to side effects of wP vaccines and formulated with aluminum hydroxide (Alum), which is not an effective adjuvant to eliminate Bordetella pertussis. Low efficiency of current aP vaccines is thought to be the main reason for the resurgence for which newer generation aP vaccines are needed. In the present study, immunogenicity and protective efficacy of outer membrane protein Q (OmpQ) and a putative lipoprotein (Lpp) from B. pertussis were investigated in mice by using two diefrent adjuvants, monophosphoryl lipid A (MPLA) or Alum. OmpQ and putative Lpp were cloned, expressed, and purified from Escherichia coli. The proteins were formulated to immunize mice. Both recombinant OmpQ and putative Lpp induced a significant increase in immunoglobulin G1 (IgG1) and immunoglobulin G2a (IgG2a) responses compared to the control group. Moreover, MPLA-adjuvanted formulations resulted in higher IgG2a levels than Alum-adjuvanted ones. However, there were no significant differences between test and control groups regarding interferon-gamma (IFN-γ) levels, and the mice lung colonization experiments indicated that neither rOmpQ nor rLpp could confer protection alone against B. pertussis challenge.

摘要

尽管在引入全细胞百日咳疫苗(wP)和无细胞百日咳疫苗(aP)后疫苗接种覆盖率很高,但许多国家仍报告了百日咳疫情的反弹。由于wP疫苗的副作用,aP疫苗通常更受青睐,并且aP疫苗是用氢氧化铝(明矾)配制的,而氢氧化铝并不是消除百日咳博德特氏菌的有效佐剂。目前aP疫苗的低效被认为是疫情反弹的主要原因,因此需要新一代的aP疫苗。在本研究中,通过使用两种不同的佐剂单磷酰脂质A(MPLA)或明矾,在小鼠中研究了百日咳博德特氏菌外膜蛋白Q(OmpQ)和一种假定的脂蛋白(Lpp)的免疫原性和保护效力。从大肠杆菌中克隆、表达并纯化了OmpQ和假定的Lpp。将这些蛋白质配制成制剂来免疫小鼠。与对照组相比,重组OmpQ和假定的Lpp均诱导免疫球蛋白G1(IgG1)和免疫球蛋白G2a(IgG2a)反应显著增加。此外,MPLA佐剂制剂产生的IgG2a水平高于明矾佐剂制剂。然而,在干扰素-γ(IFN-γ)水平方面,测试组和对照组之间没有显著差异,并且小鼠肺部定植实验表明,单独的重组OmpQ和重组Lpp均不能提供针对百日咳博德特氏菌攻击的保护。

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