LYME VACCINE BASED ON BORRELIA DECORIN ADHESIN

莱姆病疫苗的主要候选抗原，疏螺旋体 伯氏杆菌外表面是蛋白A或OspA，目前在临床上 由三家公司进行各种配方的测试，其中包括 医学免疫。基于OspA的疫苗的一个主要问题是抗体 只有在高水平存在的情况下才有效 感染，这表明感染诱导的记忆反应 Ospa将几乎没有好处。在被扁虱叮咬分娩后。 伯格多费菌在真皮中建立初始感染，真皮是一种富含 在胶原纤维中。它最近由B.Guo，M.Hook和 伯氏杆菌可以通过与胶原纤维结合的合作者 通过粘附胶原蛋白相关的蛋白多糖修饰蛋白 新型疏螺旋体粘附素粘附素结合蛋白A的相互作用 (分贝A)。我们已经在这项研究的第一阶段表明，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相当或比Ospa更好的保护，以及III)是一个目标 与Ospa不同，用于保护宿主适应的螺旋体。另外， 在第二阶段研究的小型先导性实验中，兔抗DbpA 血清能保护小鼠免受疏螺旋体的攻击。同相 在本研究中我们建议：1)确定DbpA的数量 血清保护团体，2)证明DbpA疫苗将诱导 在小鼠中对壁虱传播的伯氏杆菌攻击的保护，3) 证明将实现对DbpA的保护性抗体应答 在大型动物中，包括非人类灵长类动物，临床上 相关佐剂；4)确定主要DbpA表位(S) 以生长抑制抗体为靶点，以促进优化 疫苗投放方案。我们进一步建议，基于以下因素的疫苗 DbpA可能延长或超过以OspA为基础的疫苗的效力。 建议的商业应用： 没有莱姆病疫苗被批准用于人类，并具有免疫力 对已获批准的兽用疫苗的反应是有限的。 目前处于试验阶段的主要候选亚单位疫苗可能有限 在野外的药效。对有效疫苗的需求非常高， 特别是在莱姆病流行的地区。建议进行的研究 将产生针对体内表达的新型候选疫苗 抗原，这可能会延长或超过目前的效力 莱姆疫苗候选人。

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.