Khan Shahneaz Ali, Polkinghorne Adam, Waugh Courtney, Hanger Jon, Loader Jo, Beagley Kenneth, Timms Peter
Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Ave, Kelvin Grove, QLD 4059, Australia; Faculty of Veterinary Medicine, Chittagong Veterinary and Animal Sciences University, Khulshi, Chittagong 4202, Bangladesh.
Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Ave, Kelvin Grove, QLD 4059, Australia; Centre for Animal Health Innovation, Faculty of Science, Health, Education & Engineering, University of the Sunshine Coast, Locked Bag 4, Maroochydore DC, QLD 4558, Australia.
Vaccine. 2016 Feb 3;34(6):775-82. doi: 10.1016/j.vaccine.2015.12.050. Epub 2015 Dec 30.
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 titers/neutralising 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.
开发疫苗是对抗考拉衣原体感染广泛且使人衰弱影响的关键策略。一种正在研发的此类疫苗使用重组衣原体主要外膜蛋白(rMOMP)作为抗原,并且在多项考拉试验中显示出了有前景的结果。先前主要在小鼠模型中进行的衣原体疫苗研究表明,细胞介导的反应和抗体反应对于充分的保护都是必需的。最近,抗体的重要保护作用得到了强调。在我们当前的研究中,我们对考拉的抗体介导免疫反应进行了详细分析,这些考拉要么(a)自然感染,和/或(b)接受了rMOMP疫苗。首先,我们观察到自然感染的考拉衣原体pecorum特异性中和抗体水平非常低。在这些自然感染的动物中还观察到低IgG总滴度/中和抗体水平与较高的pecorum感染负荷之间存在强相关性。在接种疫苗的考拉中,我们表明该疫苗能够通过诱导高水平的pecorum特异性中和抗体来增强体液免疫反应。还使用PepScan表位方法对自然感染和接种疫苗的考拉中的MOMP表位反应进行了详细表征。该分析确定了自然感染未受保护和患病的考拉与接种疫苗的考拉之间MOMP表位抗体的独特集合,后一组动物产生了一组独特的特异性表位导向抗体,我们证明这些抗体负责体外中和活性。总之,这些结果表明了抗体在考拉衣原体感染和接种疫苗后的免疫中的重要性。