INCOMPLETE PROTECTION OF HAMSTERS VACCINATED WITH UNLIPIDATED OSPA FROM BORRELIA-BURGDORFERI INFECTION IS ASSOCIATED WITH LOW-LEVELS OF ANTIBODY TO AN EPITOPE DEFINED BY MAB LA-2
INCOMPLETE PROTECTION OF HAMSTERS VACCINATED WITH UNLIPIDATED OSPA FROM BORRELIA-BURGDORFERI INFECTION IS ASSOCIATED WITH LOW-LEVELS OF ANTIBODY TO AN EPITOPE DEFINED BY MAB LA-2
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DOI：
10.1016/0264-410x(95)00035-y
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发表时间：
1995-08-01
期刊：
影响因子：
5.5
通讯作者：
PIESMAN, J
中科院分区：
文献类型：
--
作者：
JOHNSON, BJB;SVIAT, SL;PIESMAN, J
开发莱姆病重组疫苗的努力集中在使用伯氏疏螺旋体的外表面蛋白A（OspA）作为免疫原。我们评估了未脂化的重组OspA作为仓鼠中的疫苗的有效性。该分子是可溶的，并且可以在大肠杆菌中以高产率产生，其特征允许简单且相对低成本的生产。用非脂化OspA接种保护了相当大一部分动物-59- 79%，取决于攻击菌株和途径-抵抗通过注射或通过感染的若虫蜱叮咬递送的中等剂量的螺旋体。疫苗失败的情况与针对特定OspA表位（由mAb LA-2定义的表位）的低水平抗体的产生相关。至少50 ng ml（-1）的LA-2等效抗体是必要的保护仓鼠。在天然OspA的高滴度多克隆抗体存在下，未受保护的动物中出现较低的LA-2等效抗体浓度。描述了定量该血清级分的竞争性结合测定，其应可用于监测疫苗试验中对OspA的抗体应答的质量。LA-2等效抗体的浓度与血清样本抑制B生长的能力平行。Burgdorferi文化
Efforts to develop a recombinant vaccine for Lyme disease have focused on using the outer surface protein A (OspA) of Borrelia burgdorferi as an immunogen. We evaluated the effectiveness of an unlipidated recombinant OspA as a vaccine in hamsters. This molecule is soluble and can be produced in high yield in Escherichia coli, characteristics that permit simple and relatively low cost production Vaccination with unlipidated OspA protected a substantial portion of animals-59-79%, depending on the challenge strain and route-against moderate doses of spirochetes delivered either by injection or by bite of infected nymphal ticks (Ixodes scapularis), The instances of vaccine failure were associated with development of low levels of antibody to a particular OspA epitope, one defined by mAb LA-2. At least 50 ng ml(-1) of LA-2 equivalent antibody was necessary for protection of hamsters. Lower LA-2 equivalent antibody concentrations occurred in unprotected animals in the presence of high-titered polyclonal antibody to native OspA. A competitive binding assay to quantitate this serum fraction is described that should be of use in monitoring the quality of the antibody response to OspA in vaccine trials. Concentrations of LA-2 equivalent antibody parallel the ability of the serum specimens to inhibit the growth of B. burgdorferi in culture.