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Therapeutic effect of a Chlamydia pecorum recombinant major outer membrane protein vaccine on ocular disease in koalas (Phascolarctos cinereus)

机译:衣原体重组主要外膜蛋白疫苗对无尾熊眼病的治疗作用

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摘要

Chlamydia pecorum is responsible for causing ocular infection and disease which can lead to blindness in koalas (Phascolarctos cinereus). Antibiotics are the current treatment for chlamydial infection and disease in koalas, however, they can be detrimental for the koala’s gastrointestinal tract microbiota and in severe cases, can lead to dysbiosis and death. In this study, we evaluated the therapeutic effects provided by a recombinant chlamydial major outer membrane protein (MOMP) vaccine on ocular disease in koalas. Koalas with ocular disease (unilateral or bilateral) were vaccinated and assessed for six weeks, evaluating any changes to the conjunctival tissue and discharge. Samples were collected pre- and post-vaccination to evaluate both humoral and cell-mediated immune responses. We further assessed the infecting C. pecorum genotype, host MHC class II alleles and presence of koala retrovirus type (KoRV-B). Our results clearly showed an improvement in the clinical ocular disease state of all seven koalas, post-vaccination. We observed increases in ocular mucosal IgA antibodies to whole C. pecorum elementary bodies, post-vaccination. We found that systemic cell-mediated immune responses to interferon-γ, interleukin-6 and interleukin-17A were not significantly predictive of ocular disease in koalas. Interestingly, one koala did not have as positive a clinical response (in one eye primarily) and this koala was infected with a C. pecorum genotype (E’) that was not used as part of the vaccine formula (MOMP genotypes A, F and G). The predominant MHC class II alleles identified were DAb*19, DAb*21 and DBb*05, with no two koalas identified with the same genetic sequence. Additionally, KoRV-B, which is associated with chlamydial disease outcome, was identified in two (29%) ocular diseased koalas, which still produced vaccine-induced immune responses and clinical ocular improvements post-vaccination. Our findings show promise for the use of a recombinant chlamydial MOMP vaccine for the therapeutic treatment of ocular disease in koalas.
机译:pecorum pecorum是造成眼部感染和疾病的原因,它可能导致无尾熊(Phascolarctos cinereus)失明。抗生素是目前治疗考拉衣原体感染和疾病的方法,但是,它们可能对考拉的胃肠道微生物群有害,在严重的情况下,可能导致营养不良和死亡。在这项研究中,我们评估了重组衣原体主要外膜蛋白(MOMP)疫苗对无尾熊眼病的治疗效果。对患有眼病(单侧或双侧)的考拉进行了疫苗接种并评估了六个星期,以评估结膜组织和分泌物的任何变化。接种前后收集样品,以评估体液和细胞介导的免疫反应。我们进一步评估了感染衣原体基因型,宿主MHC II类等位基因和考拉逆转录病毒类型(KoRV-B)的存在。我们的结果清楚地表明,接种疫苗后所有七个考拉的临床眼部疾病状况均有改善。我们观察到,接种疫苗后,整个粘膜梭菌基本体的眼粘膜IgA抗体增加。我们发现对干扰素-γ,白介素-6和白介素-17A的全身细胞介导的免疫反应不能显着预测考拉的眼部疾病。有趣的是,一只考拉没有表现出阳性的临床反应(主要是一只眼睛),并且这种考拉感染了不被用作疫苗配方(MOMP基因型A,F和B)的一部分的库克氏梭菌基因型(E')。 G)。鉴定出的主要II类MHC等位基因是DAb * 19,DAb * 21和DBb * 05,没有两个考拉具有相同的遗传序列。此外,在两个(29%)眼部感染的考拉中发现了与衣原体疾病结局相关的KoRV-B,它们在疫苗接种后仍能产生疫苗诱导的免疫反应和临床眼部改善。我们的发现表明有望将重组衣原体MOMP疫苗用于治疗考拉的眼部疾病。

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