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Humoral immune responses in koalas (Phascolarctos cinereus) either naturally infected with Chlamydia pecorum or following administration of a recombinant chlamydial major outer membrane protein vaccine

机译:自然感染了衣原体衣原体或施用重组衣原体主要外膜蛋白疫苗后的考拉(Phascolarctos cinereus)体液免疫反应

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The development of a vaccine is a key strategy to combat the widespread and debilitating effects of chlamydial infection in koalas. One such vaccine in development uses recombinant chlamydial major outer membrane protein (rMOMP) as an antigen and has shown promising results in several koala trials. Previous chlamydial vaccine studies, primarily in the mouse model, suggest that both cell-mediated and antibody responses will be required for adequate protection. Recently, the important protective role of antibodies has been highlighted. In our current study, we conducted a detailed analysis of the antibody mediated immune response in koalas that are either (a) naturally-infected, and/or (b) had received an rMOMP vaccine. Firstly, we observed that naturally-infected koalas had very low levels of Chlamydia pecorum-specific neutralising antibodies. A strong correlation between low IgG total titerseutralising antibody levels, and higher C pecorum infection load was also observed in these naturally-infected animals. In vaccinated koalas, we showed that the vaccine was able to boost the humoral immune response by inducing strong levels of C. pecorum-specific neutralising antibodies. A detailed characterisation of the MOMP epitope response was also performed in naturally-infected and vaccinated koalas using a PepScan epitope approach. This analysis identified unique sets of MOMP epitope antibodies between naturally infected non-protected and diseased koalas, versus vaccinated koalas, with the latter group of animals producing a unique set of specific epitope-directed antibodies that we demonstrated were responsible for the in vitro neutralisation activity. Together, these results show the importance of antibodies in chlamydial infection and immunity following vaccination in the koala. (C) 2015 Elsevier Ltd. All rights reserved.
机译:疫苗的开发是对抗考拉衣原体感染的广泛且破坏性作用的关键策略。一种正在开发的疫苗使用重组衣原体主要外膜蛋白(rMOMP)作为抗原,并在多项考拉试验中显示出令人鼓舞的结果。以前的衣原体疫苗研究,主要是在小鼠模型中,表明细胞介导的和抗体的应答都需要适当的保护。最近,抗体的重要保护作用已得到强调。在我们目前的研究中,我们对(a)自然感染和/或(b)接受了rMOMP疫苗的考拉中抗体介导的免疫反应进行了详细分析。首先,我们观察到自然感染的考拉的衣原体衣原体特异性中和抗体水平非常低。在这些自然感染的动物中,还发现低IgG总滴度/中和抗体水平与较高的pecorum感染量之间存在很强的相关性。在接种疫苗的考拉中,我们证明了该疫苗能够通过诱导高水平的角膜梭菌特异性中和抗体来增强体液免疫反应。还使用PepScan表位方法在自然感染和接种的考拉中对MOMP表位反应进行了详细表征。这项分析确定了自然感染的未保护和患病的考拉与已接种的考拉之间独特的MOMP表位抗体组,后一组动物产生了一组独特的特异性表位导向抗体,我们证明了它们负责体外中和活性。总之,这些结果表明抗体在考拉疫苗接种后在衣原体感染和免疫中的重要性。 (C)2015 Elsevier Ltd.保留所有权利。

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