LYME VACCINE BASED ON BORRELIA DECORIN ADHESIN

莱姆病疫苗的主要候选抗原， 目前临床上， 三家公司在各种配方中进行测试，其中 医学免疫基于OspA的疫苗的一个主要问题是， 只有在高水平存在之前， 感染，这表明感染引起的记忆反应， OspA将带来很少或根本没有好处。分娩后被蜱虫叮咬B。 burgdorferi在真皮中建立初始感染， 在胶原纤维中。它最近被B展示。Guo，M.钩和 B. burgdorferi可以通过 粘附于胶原蛋白相关蛋白多糖核心蛋白聚糖， 与新的疏螺旋体粘附素核心蛋白聚糖结合蛋白A的相互作用 （DbpA）。我们已经在本研究的I期中表明，DbpA：i）具有 作为莱姆病实验疫苗的有效性，ii）具有血清学 与OspA相当或更好的保护，iii）是目标 用于保护宿主适应性螺旋体，不像OspA。此外，本发明还 在II期研究的小型先导实验中，兔抗DbpA 血清保护小鼠免受蜱叮咬的疏螺旋体攻击。同相 本研究的第二部分我们提出：1）确定DbpA的数量 血清保护组，2）证明DbpA疫苗将引起 防止蜱传B。小鼠中的伯氏菌攻击，3） 证明将实现对DbpA的保护性抗体应答 在较大的动物中，包括非人灵长类动物，临床上 相关佐剂，和4）鉴定主要DbpA表位 通过生长抑制抗体靶向，以促进优化 疫苗运送协议我们进一步建议， DbpA可以延长或超过基于OspA的疫苗的效力。 拟定商业应用： 没有莱姆病疫苗被批准用于人类使用， 对批准的兽用疫苗的反应持续时间有限。 目前处于试验阶段的主要候选亚单位疫苗可能具有有限的 在外地的功效。对有效疫苗的需求非常高， 特别是在莱姆病流行的地区。拟议的研究 将产生靶向体内表达的新型疫苗候选物， 抗原，并且可以延长或超过当前免疫疗法的功效。 莱姆病疫苗候选人。

The leading candidate antigen for a Lyme disease vaccine, the Borrelia burgdorferi outer surface is protein A or OspA is currently in clinical testing in various formulations by three companies, among them MedImmune. A major concern for OspA-based vaccines is that antibodies against this protein are effective only if present at high levels prior to infection, suggesting that an infection-induced memory response to OspA will be of little or no benefit. After delivery by a tick bite B. burgdorferi establishes an initial infection in the dermis, a site rich in collagen fibers. It has recently been shown by B. Guo, M. Hook and collaborators that B. burgdorferi can bind to collagen fibers through adhesion to the collagen-associated proteoglycan decorin through interactions with the novel borrelia adhesin decorin binding protein A (DbpA). We have shown in Phase I of this study that DbpA: i) had efficacy as an experimental vaccine for Lyme disease, ii) had serologic conservation comparable to, or better than, OspA, and iii) was a target for protection on host-adapted spirochetes, unlike OspA. Additionally, in a small pilot experiment toward a Phase II study, rabbit anti-DbpA serum protected mice against borrelia challenge by tick bite. In Phase II of this study we propose to: 1) determine the number of DbpA seroprotective groups, 2) demonstrate that DbpA vaccines will elicit protection against tick-borne B. burgdorferi challenge in mice, 3) demonstrate that protective antibody responses to DbpA will be achieved in larger animals, including non-human primates, with clinically relevant adjuvants, and 4) identify the principal DbpA epitope(s) targeted by growth-inhibitory antibodies to facilitate optimization of vaccine delivery protocols. We further propose that vaccines based on DbpA may extend, or surpass, the efficacy of OspA-based vaccines. PROPOSED COMMERCIAL APPLICATION: No vaccine for Lyme disease is approved for human use, and immune responses to the approved veterinary vaccine are of limited duration. The lead candidate subunit vaccines now in trials may have limited efficacy in the field. The demand for an effective vaccine is very high, particularly in areas endemic for Lyme disease. The proposed studies will yield novel vaccine candidates that target in vivo expressed antigens, and that may extend, or surpass, the efficacy of the current Lyme vaccine candidate.