Pfeifle Annabelle, Thulasi Raman Sathya N, Lansdell Casey, Zhang Wanyue, Tamming Levi, Cecillon Jonathon, Laryea Emmanuel, Patel Devina, Wu Jianguo, Gravel Caroline, Frahm Grant, Gao Jun, Chen Wangxue, Chaconas George, Sauve Simon, Rosu-Myles Michael, Wang Lisheng, Johnston Michael J W, Li Xuguang
Centre for Oncology, Radiopharmaceuticals and Research, Biologic and Radiopharmaceutical Drugs Directorate, Health Products and Food Branch, Health Canada and World Health Organization Collaborating Center for Standardization and Evaluation of Biologicals, Ottawa, ON, Canada.
Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
Front Immunol. 2023 Mar 16;14:1020134. doi: 10.3389/fimmu.2023.1020134. eCollection 2023.
The incidence of Lyme disease (LD) in Canada and the United States has risen over the last decade, nearing 480,000 cases each year. sensu lato, the causative agent of LD, is transmitted to humans through the bite of an infected tick, resulting in flu-like symptoms and often a characteristic bull's-eye rash. In more severe cases, disseminated bacterial infection can cause arthritis, carditis and neurological impairments. Currently, no vaccine is available for the prevention of LD in humans.
In this study, we developed a lipid nanoparticle (LNP)-encapsulated DNA vaccine encoding outer surface protein C type A (OspC-type A) of
Vaccination of C3H/HeN mice with two doses of the candidate vaccine induced significant OspC-type A-specific antibody titres and borreliacidal activity. Analysis of the bacterial burden following needle challenge with (OspC-type A) revealed that the candidate vaccine afforded effective protection against homologous infection across a range of susceptible tissues. Notably, vaccinated mice were protected against carditis and lymphadenopathy associated with Lyme borreliosis.
Overall, the results of this study provide support for the use of a DNA-LNP platform for the development of LD vaccines.
在过去十年中，加拿大和美国的莱姆病（LD）发病率有所上升，每年接近48万例。广义上，LD的病原体通过受感染蜱虫的叮咬传播给人类，导致类似流感的症状，通常还会出现特征性的靶心皮疹。在更严重的情况下，细菌的播散性感染可导致关节炎、心肌炎和神经功能障碍。目前，尚无用于预防人类LD的疫苗。
在本研究中，我们开发了一种脂质纳米颗粒（LNP）包裹的DNA疫苗，该疫苗编码A 型外表面蛋白C（OspC-A型）。
用两剂候选疫苗对C3H/HeN小鼠进行接种可诱导产生显著的OspC-A型特异性抗体滴度和杀螺旋体活性。在用（OspC-A型）进行针刺攻击后分析细菌负荷发现，候选疫苗在一系列易感组织中提供了针对同源感染的有效保护。值得注意的是，接种疫苗的小鼠对与莱姆病相关的心肌炎和淋巴结病具有抵抗力。
总体而言，本研究结果为使用DNA-LNP平台开发LD疫苗提供了支持。
