Design of a broadly reactive Lyme disease vaccine
Design of a broadly reactive Lyme disease vaccine
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DOI：
10.1038/s41541-020-0183-8
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发表时间：
2020-05-01
期刊：
影响因子：
9.2
通讯作者：
Nabel, Gary J.
中科院分区：
文献类型：
--
作者：
Kamp, Heather D.;Swanson, Kurt A.;Nabel, Gary J.
莱姆病是全球日益关注的健康问题，已成为美国和欧洲最常见的蜱传疾病。这种疾病由细菌螺旋体伯氏疏螺旋体 (Sl) 引起，如果不及时治疗，可能会使人衰弱。由于诊断具有挑战性，预防仍然是重中之重；然而，之前获得许可的疫苗不再向公众提供。在这里，我们设计了一种六成分疫苗，可引发针对所有通常引起人类莱姆病的疏螺旋体菌株的抗体 (Ab) 反应。将疏螺旋体的外表面蛋白 A (OspA) 与细菌铁蛋白融合，生成自组装纳米颗粒。 OspA-铁蛋白纳米颗粒在小鼠和非人类灵长类动物中引发了针对七种主要血清型的持久高滴度抗体反应，其滴度高于之前许可的疫苗。这种反应在恒河猴中持续了 6 个多月。在蜱喂养的小鼠攻击模型中，含佐剂的 OspA-铁蛋白纳米颗粒疫苗接种可刺激针对伯氏疏螺旋体和阿氏疏螺旋体感染的保护性免疫力。这种多价莱姆病疫苗具有限制莱姆病传播的潜力。
A growing global health concern, Lyme disease has become the most common tick-borne disease in the United States and Europe. Caused by the bacterial spirochete Borrelia burgdorferi sensu lato (sl), this disease can be debilitating if not treated promptly. Because diagnosis is challenging, prevention remains a priority; however, a previously licensed vaccine is no longer available to the public. Here, we designed a six component vaccine that elicits antibody (Ab) responses against all Borrelia strains that commonly cause Lyme disease in humans. The outer surface protein A (OspA) of Borrelia was fused to a bacterial ferritin to generate self-assembling nanoparticles. OspA-ferritin nanoparticles elicited durable high titer Ab responses to the seven major serotypes in mice and non-human primates at titers higher than a previously licensed vaccine. This response was durable in rhesus macaques for more than 6 months. Vaccination with adjuvanted OspA-ferritin nanoparticles stimulated protective immunity from both B. burgdorferi and B. afzelii infection in a tick-fed murine challenge model. This multivalent Lyme vaccine offers the potential to limit the spread of Lyme disease.