Department of Veterinary Pathobiology, Texas A&M University, TAMU-4467, College Station, Texas 77843-4467, United States; Department of Internal and Preventive Veterinary Medicine, University of Mosul, Mosul, Iraq.
Department of Veterinary Pathobiology, Texas A&M University, TAMU-4467, College Station, Texas 77843-4467, United States.
Vaccine. 2019 Sep 3;37(37):5596-5606. doi: 10.1016/j.vaccine.2019.07.092. Epub 2019 Aug 3.
Lyme disease (LD) accounts for over 70% of tick-borne disease reported in the United States. The disease in humans is characterized by skin rash, arthritis, cardiac and neurological signs. Vaccination is the most efficient preventive measure that could be taken to reduce the incidence of the LD worldwide; however, at present no vaccine is available. In this study, evaluation of the Borrelia burgdorferi BB0172-derived peptide (PepB) in conjugated formulations was investigated as a vaccine candidate in murine model of LD. In brief, PepB was conjugated to the Cross-Reacting Material 197 (CRM197) and to Tetanus Toxoid heavy chain (TTHc) molecules, and subsequently used to immunize C3H/HeN mice. Following the challenge with 10 spirochetes/mouse via subcutaneous inoculation, TTHc:PepB construct showed protection in 66% of the immunized animals. Hence, to further evaluate the efficacy of TTHc:PepB, immunized mice were challenged with B. burgdorferi using the tick model of infection. The outcome of this experiment revealed that serum from TTHc:PepB immunized mice was borrelicidal. After tick infection, bacterial burden was significantly reduced (over 70%) in vaccinated animals when compared with the control groups regardless of whether the mice were infested 8 or 12-weeks post-priming. Therefore, we conclude that PepB conjugated antigens can serve as an alternative to prevent LD; nevertheless, further studies will be needed to dissect the mechanisms by which anti-PepB IgG antibodies are able to kill B. burgdorferi in vitro and in vivo to further advance in the development of formulations and delivery alternative to generate a safe anti-LD vaccine.
莱姆病（LD）占美国报告的 ticks-borne 疾病的 70%以上。人类疾病的特征是皮疹、关节炎、心脏和神经系统症状。接种疫苗是减少全球 LD 发病率的最有效预防措施；然而，目前尚无疫苗可用。在这项研究中，评估了 Borrelia burgdorferi BB0172 衍生肽（PepB）在缀合制剂中的作用，作为 LD 小鼠模型中的候选疫苗。简而言之，PepB 与交叉反应物质 197（CRM197）和破伤风类毒素重链（TTHc）分子缀合，随后用于免疫 C3H/HeN 小鼠。通过皮下接种 10 个螺旋体/只小鼠进行挑战后，TTHc：PepB 构建体在 66%的免疫动物中显示出保护作用。因此，为了进一步评估 TTHc：PepB 的功效，用感染 tick 的小鼠模型对免疫小鼠进行了 B. burgdorferi 挑战。该实验的结果表明，TTHc：PepB 免疫小鼠的血清具有杀菌作用。在 tick 感染后，与对照组相比，无论接种后 8 周还是 12 周是否有 tick 感染，TTHc：PepB 免疫动物的细菌负荷均显著降低（超过 70%）。因此，我们得出结论，PepB 缀合抗原可以作为预防 LD 的替代方法；然而，需要进一步研究来剖析抗 PepB IgG 抗体在体外和体内杀死 B. burgdorferi 的机制，以进一步推进制剂的开发和替代给药方式，从而开发出安全的抗 LD 疫苗。
