Lizárraga David, Timms Peter, Quigley Bonnie L, Hanger Jon, Carver Scott
School of Natural Sciences, University of Tasmania, Hobart, TAS, Australia.
Genecology Research Centre, School of Science and Engineering, University of Sunshine Coast, Sippy Downs, QLD, Australia.
Front Vet Sci. 2020 Sep 25;7:530686. doi: 10.3389/fvets.2020.530686. eCollection 2020.
Chlamydial disease is a major factor negatively affecting koala populations. Vaccination is a promising management option that would result in immune-mediated protection against disease. Measuring and assessing vaccine efficacy can be challenging owing to both direct and indirect interactions caused by vaccination. In this study, we investigate vaccine-immune-chlamydial load-disease relationships from MOMP (major outer membrane protein) vaccine trials to protect healthy free-ranging koalas against -related diseases. We created hypotheses based on data sources and perceived direct and indirect interactions from koalas vaccinated 6 months prior. Each hypothesis was tested as a structural equation model separately for either the urogenital or the ocular site to evaluate possible causality among measured variables. Model averaging was used as multiple models fit the data, and the strength of relationships was examined through averaged coefficients and the raw data. We found more relationships in urogenital models as compared to ocular models, particularly those with interleukin 17 (IL17) mRNA expression compared to models with interferon gamma (IFNγ) expression. In the averaged model with IL17, urogenital chlamydial load was positively associated with disease and negatively associated with IL17 expression. MOMP vaccination had a trending effect for reducing urogenital chlamydial load and also had a strong effect on increasing IL17 expression. Not surprisingly, urogenital chlamydial load was a positive predictor for the development of urogenital disease at 6 months post-vaccination. Despite multiple potential sources of variation owing to the koalas in this study being free-ranging, our analyses provide unique insights into the effects of vaccinating against . Using structural equation modeling, this study has helped illuminate that the expression of the immune cytokine IL17 is linked to MOMP vaccination, and animals with a high urogenital chlamydial load expressed less IL17 and were more likely to develop disease, enhancing previous investigations. Going beyond univariate statistics, the methods used in this study can be applied to other preclinical vaccination experiments to identify important direct and indirect factors underpinning the effects of a vaccine.
衣原体病是对考拉种群产生负面影响的一个主要因素。疫苗接种是一种很有前景的管理方法，有望产生针对疾病的免疫介导保护作用。由于疫苗接种引起的直接和间接相互作用，测量和评估疫苗效力可能具有挑战性。在本研究中，我们从主要外膜蛋白（MOMP）疫苗试验来研究疫苗 - 免疫 - 衣原体载量 - 疾病之间的关系，以保护健康的野生考拉免受相关疾病侵害。我们基于数据来源以及对6个月前接种疫苗的考拉的直接和间接相互作用的认知创建了假设。每个假设都作为结构方程模型分别针对泌尿生殖部位或眼部进行测试，以评估测量变量之间可能的因果关系。由于多个模型都符合数据，因此使用了模型平均法，并通过平均系数和原始数据来检验关系的强度。与眼部模型相比，我们在泌尿生殖模型中发现了更多的关系，特别是与那些具有干扰素γ（IFNγ）表达的模型相比，具有白细胞介素17（IL17）mRNA表达的模型。在具有IL17的平均模型中，泌尿生殖部位的衣原体载量与疾病呈正相关，与IL17表达呈负相关。MOMP疫苗接种对降低泌尿生殖部位的衣原体载量有一定趋势性影响，并且对增加IL17表达也有很强的作用。不出所料，泌尿生殖部位的衣原体载量是疫苗接种后6个月泌尿生殖疾病发生的一个积极预测指标。尽管本研究中的考拉由于是野生的而存在多种潜在的变异来源，但我们的分析为接种疫苗的效果提供了独特的见解。通过使用结构方程模型，本研究有助于阐明免疫细胞因子IL17的表达与MOMP疫苗接种有关，泌尿生殖部位衣原体载量高的动物表达的IL17较少，并且更有可能发病，这进一步完善了先前的研究。本研究中使用的方法超越了单变量统计，可以应用于其他临床前疫苗接种实验，以确定支撑疫苗效果的重要直接和间接因素。
