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

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.兽衣原体（Chlamydia pecorum）可引发考拉（树袋熊，Phascolarctos cinereus）的眼部感染与相关疾病，严重时可导致宿主失明。当前针对考拉衣原体感染及相关病症的临床治疗手段以抗生素为主，但抗生素会对考拉的胃肠道微生物群造成损伤，重症病例中甚至会引发菌群失调乃至死亡。本研究评估了重组衣原体主要外膜蛋白（MOMP）疫苗对考拉眼部疾病的治疗效果。研究人员对接诊的单侧或双侧眼部患病考拉进行疫苗接种，并开展为期六周的随访评估，对其结膜组织与眼部分泌物的变化进行评估。分别在疫苗接种前与接种后采集样本，以检测宿主的体液免疫与细胞免疫应答情况。此外，本研究还对感染的兽衣原体基因型、宿主主要组织相容性复合体（MHC）II类等位基因以及考拉逆转录病毒B型（KoRV-B）的携带状态进行了分析。研究结果显示，全部7只接种疫苗的考拉的眼部临床疾病状态均得到显著改善。疫苗接种后，考拉眼部黏膜针对完整兽衣原体原体的免疫球蛋白A（IgA）抗体水平明显升高。研究发现，针对干扰素-γ（interferon-γ）、白细胞介素-6（interleukin-6）与白细胞介素-17A（interleukin-17A）的系统性细胞免疫应答，无法有效预判考拉眼部疾病的转归。值得注意的是，有1只考拉仅单眼出现临床改善效果欠佳的情况，该个体感染的兽衣原体基因型（E’）未被纳入本次疫苗配方所涵盖的MOMP基因型（A、F与G）。本研究鉴定出的主要MHC II类等位基因为DAb*19、DAb*21与DBb*05，未观察到两只考拉携带完全相同的基因序列。另外，2只（占比29%）眼部患病考拉携带与衣原体疾病预后相关的KoRV-B，但它们仍能产生疫苗诱导的免疫应答，并在接种后实现眼部临床症状的改善。本研究结果表明，重组衣原体MOMP疫苗用于治疗考拉眼部疾病展现出良好的应用潜力。