Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, USA.
Texas A&M Institute for Genomic Sciences and Society, Texas A&M University, College Station, Texas, USA.
Infect Immun. 2019 Jun 20;87(7). doi: 10.1128/IAI.00164-19. Print 2019 Jul.
is a tick-borne bacterium responsible for approximately 300,000 annual cases of Lyme disease (LD) in the United States, with increasing incidences in other parts of the world. The debilitating nature of LD is mainly attributed to the ability of to persist in patients for many years despite strong anti- antibody responses. Antimicrobial treatment of persistent infection is challenging. Similar to infection of humans, establishes long-term infection in various experimental animal models except for New Zealand White (NZW) rabbits, which clear the spirochete within 4 to 12 weeks. LD spirochetes have a highly evolved antigenic variation system, on the lp28-1 plasmid, where gene conversion results in surface expression of the antigenically variable VlsE protein. VlsE is required for to establish persistent infection by continually evading otherwise potent antibodies. Since the clearance of is mediated by humoral immunity in NZW rabbits, the previously reported results that LD spirochetes lose lp28-1 during rabbit infection could potentially explain the failure of to persist. However, the present study unequivocally disproves that previous finding by demonstrating that LD spirochetes retain the system. However, despite the system being fully functional, the spirochete fails to evade anti- antibodies of NZW rabbits. In addition to being protective against homologous and heterologous challenges, the rabbit antibodies significantly ameliorate LD-induced arthritis in persistently infected mice. Overall, the current data indicate that NZW rabbits develop a protective antibody repertoire, whose specificities, once defined, will identify potential candidates for a much-anticipated LD vaccine.
是一种蜱传细菌，导致美国每年约有 30 万例莱姆病（LD）病例，在世界其他地区的发病率也在上升。LD 的致残性质主要归因于 的能力，尽管存在强烈的抗抗体反应，但仍能在患者体内持续存在多年。持续性感染的抗菌治疗具有挑战性。与人类感染相似， 在各种实验动物模型中建立长期感染，除了新西兰白兔（NZW），NZW 兔在 4 至 12 周内清除螺旋体。LD 螺旋体具有高度进化的抗原变异 系统，位于 lp28-1 质粒上，基因转换导致抗原可变 VlsE 蛋白的表面表达。VlsE 是 建立持续性感染所必需的，通过不断逃避有效的抗体。由于 NZW 兔中的体液免疫介导了 的清除，先前报道的 LD 螺旋体在兔感染期间丢失 lp28-1 的结果可能解释了 未能持续存在的原因。然而，本研究通过证明 LD 螺旋体保留了 系统，明确否定了先前的发现。然而，尽管 系统完全发挥功能，螺旋体仍未能逃避 NZW 兔的抗抗体。除了对同源和异源挑战具有保护作用外，兔抗体还显著改善了持续感染小鼠的 LD 诱导关节炎。总的来说，目前的数据表明，NZW 兔产生了保护性抗体库，一旦确定其特异性，将为人们期待已久的 LD 疫苗确定潜在的候选者。
