Moredun Research Institute, Pentlands Science Park, Bush Loan, Edinburgh, Midlothian EH26 0PZ, United Kingdom.
Moredun Research Institute, Pentlands Science Park, Bush Loan, Edinburgh, Midlothian EH26 0PZ, United Kingdom.
Vaccine. 2018 Jun 14;36(25):3593-3598. doi: 10.1016/j.vaccine.2018.05.042.
The live, temperature-attenuated vaccine strain 1B of Chlamydia abortus, the aetiological agent of ovine enzootic abortion (OEA), has been implicated in cases of vaccine breakdown. The aim of this study was to understand the nature of this attenuation through sequencing of the vaccine parent strain (AB7) and the derived mutant strains 1B and 1H, as well as to clarify the role of the vaccine strain in causing disease through comparative whole genome analysis.
Whole genome sequencing was performed on: vaccine parent strain AB7; N-methyl-N'-nitro-N-nitrosoguanidine (NTG)-induced temperature attenuated mutant strain 1B grown from the commercial live vaccines Cevac Chlamydia and Enzovax; strain 1H a reverted NTG mutant; and 5 strains isolated from cases of OEA originating from animals from the original vaccine safety trial (2 strains) or from vaccinated ewes or ewes exposed to vaccinated animals (3 strains).
We confirmed that AB7 is in a different lineage from the reference strain S26/3. The genome of vaccine strain 1B contains ten single nucleotide polymorphisms (SNPs) created by the NTG treatment, which are identical to those found in strain 1H. The strains from OEA cases also cluster phylogenetically very tightly with these vaccine strains.
The results show that C. abortus vaccine strain 1B has an identical genome sequence to the non-attenuated "reverted mutant" strain 1H. Thus, the protection of the 1B vaccine is unlikely to be due to the NTG induced SNPs and is more likely caused by the administration of high doses of C. abortus elementary bodies that stimulate protective immunity. Vaccine-identical strains were also isolated from cases of disease, as well as strains which had acquired 1-3 SNPs, including an animal that had not been vaccinated with either of the commercial live OEA vaccines, indicating that the 1B vaccine strain may be circulating and causing disease.
绵羊地方性流产（Ovine enzootic abortion，OEA）的病原体沙眼衣原体 1B 活减毒疫苗株已被认为与疫苗失效病例有关。本研究旨在通过对疫苗亲本株（AB7）和衍生的突变株 1B 和 1H 进行测序，了解这种减毒的性质，并通过比较全基因组分析阐明疫苗株在引起疾病中的作用。
对以下菌株进行全基因组测序：疫苗亲本株 AB7；N-甲基-N'-硝基-N-亚硝基胍（NTG）诱导的温度减毒株 1B，来自商业活疫苗 Cevac Chlamydia 和 Enzovax；NTG 回复突变株 1H；以及从源自原始疫苗安全性试验动物的 OEA 病例中分离的 5 株（2 株）或从接种过疫苗的绵羊或接触过接种过疫苗动物的绵羊中分离的 3 株。
我们证实 AB7 与参考株 S26/3 属于不同谱系。疫苗株 1B 的基因组包含 10 个由 NTG 处理产生的单核苷酸多态性（SNP），与 1H 中发现的 SNP 完全相同。OEA 病例中的菌株也与这些疫苗株在系统发育上非常紧密地聚类。
结果表明，衣原体流产疫苗株 1B 与非减毒株“回复突变株”1H 的基因组序列完全相同。因此，1B 疫苗的保护作用不太可能是由于 NTG 诱导的 SNP 引起的，而更可能是由于给予高剂量的衣原体流产原生小体刺激保护性免疫。从疾病病例中也分离到了与疫苗相同的菌株，以及获得 1-3 个 SNP 的菌株，包括未接种过两种商业活 OEA 疫苗的动物，表明 1B 疫苗株可能在传播并引起疾病。
