Diversity of antibody responses to Borrelia burgdorferi in experimentally-infected beagle dogs

Lyme borreliosis (LB) is a common infection of domestic dogs in areas where there is enzootic transmission of the agent Borrelia burgdorferi. Immunodiagnostic assays for canine antibodies to B. burgdorferi are usually based on whole-cell preparations as substrate and, consequently, interpretation of results is confounded by antibody cross-reactivity between borrelial antigens and those of other bacterial species. To more broadly characterize the antibody responses to B. burgdorferi infection and to assess the diversity in those responses between individual dogs, we examined sera from 32 adult, colony-bred beagle dogs that were experimentally infected with B. burgdorferi through tick bites and compared those on a protein microarray with sera from uninfected dogs in their antibody reactivities to various recombinant chromosome- and plasmid-encoded B. burgdorferi proteins, including 24 of the serotype-defining OspC proteins of North America. The profiles of immunogenic proteins for the dogs were largely similar to those for humans and natural reservoir rodents. These included the decorin-binding protein DbpB, BBA36, BBA57, BBA64, fibronectin-binding protein BBK32, VlsE, FlaB and other flagellar structural proteins, Erp proteins, Bdr proteins, and all of the OspC proteins. In addition, the canine sera bound to the presumptive lipoproteins BBB14 and BB0844, which infrequently elicited antibodies in humans or rodents. Although the beagle, like most other domestic dog breeds, has a small effective population size and features extensive linkage disequilibrium, the group of animals here demonstrated diversity in antibody responses by measures of antibody levels and specificities for conserved proteins, like DbpB, and polymorphic ones, like OspC. Antibody profiling was performed on sera from dogs experimentally-infected with B. burgdorferi and unexposed controls against antigens of B. burgdorferi. Thirty-two serum samples from experimental infections, and 4 unexposed controls were probed on a protein microarray displaying 72 unique proteins of B. burgdorferi .

莱姆疏螺旋体病（Lyme borreliosis, LB）是伯氏疏螺旋体（Borrelia burgdorferi）存在地方性传播区域内，家犬的常见感染性疾病。目前针对犬抗伯氏疏螺旋体抗体的免疫诊断检测，通常以全细胞制备物作为底物，因此伯氏疏螺旋体抗原与其他细菌物种抗原间的抗体交叉反应，常会干扰检测结果的判读。为更全面地表征犬对伯氏疏螺旋体感染的抗体应答，并评估个体犬间应答的多样性，本研究采集了32只通过蜱虫叮咬实验感染伯氏疏螺旋体的繁殖群饲养成年比格犬的血清，并借助蛋白质微阵列，对比该血清与未感染犬血清对多种重组染色体及质粒编码的伯氏疏螺旋体蛋白的抗体反应性，其中包含24种北美血清型定型的OspC蛋白。犬的免疫原性蛋白谱与人类以及自然储存宿主啮齿类动物的免疫原性蛋白谱大体相似，包括结合核心蛋白聚糖的DbpB、BBA36、BBA57、BBA64、纤连蛋白结合蛋白BBK32、VlsE、FlaB及其他鞭毛结构蛋白、Erp蛋白、Bdr蛋白，以及所有OspC蛋白。此外，犬血清可与推定的脂蛋白BBB14及BB0844结合，这类蛋白在人类或啮齿类动物中极少诱导抗体产生。尽管比格犬与多数其他家犬品种一样，有效种群规模较小且存在广泛的连锁不平衡特征，但本研究的受试犬群通过抗体水平及特异性（针对DbpB等保守蛋白与OspC等多态蛋白）的检测，展现出抗体应答的多样性。本研究针对实验感染伯氏疏螺旋体的犬及未暴露对照犬的血清，开展了伯氏疏螺旋体抗原的抗体谱分析。研究共使用72种独特的伯氏疏螺旋体蛋白构建蛋白质微阵列，对32份实验感染血清样本与4份未暴露对照血清进行了杂交检测。