Identification of a defined linear epitope in the OspA protein of the Lyme disease spirochetes that elicits bactericidal antibody responses: Implications for vaccine development.
Identification of a defined linear epitope in the OspA protein of the Lyme disease spirochetes that elicits bactericidal antibody responses: Implications for vaccine development.
复制标题
DOI：
10.1016/j.vaccine.2017.04.079
复制
发表时间：
2017-05-31
期刊：
影响因子：
5.5
通讯作者：
Marconi RT
中科院分区：
文献类型：
--
作者：
Izac JR;Oliver LD Jr;Earnhart CG;Marconi RT
脂蛋白OspA由莱姆病螺旋体主要在未进食的蜱中产生。OspA的产生被血粉下调，并且除了在患有莱姆关节炎的患者的晚期感染期间可能的短暂产生之外，它不在哺乳动物中产生。用OspA激发抗体（Ab）接种疫苗，该抗体可在进食期间靶向蜱中肠中的螺旋体并抑制传播至哺乳动物。OspA是人LYMErix™疫苗的主要组分。LYMErix™于1998年至2002年上市，但由于对疫苗接种引起的不良事件和疗效不佳的未经证实的担忧导致销售下降而退出市场。据推测，OspA的区段与人LFA-1中的区域共享序列相似性，并且可以触发推定的自身免疫事件。虽然支持这种联系的证据尚未得到证实，但推动OspA作为疫苗组成部分的大多数努力都试图消除这一令人关切的区域。在此，我们鉴定了定位于OspA氨基酸残基221-240（OspA 221 -240）内的OspA线性表位，其缺乏提示引发自身免疫的OspA区域。由残基221-240组成的肽在小鼠中具有免疫原性。针对OspA 221 -240肽表面标记的B产生的Ab。在IFAs中检测到伯氏螺旋体，并显示出有效的Ab介导的补体依赖性杀菌活性。BLAST分析鉴定了OspA 221 -240的几种变体和OspB中的密切相关序列。我们的假设是，将OspA 221 -240表位整合到基于多价OspC的嵌合表位的疫苗抗原（嵌合位）中可以产生通过协同机制保护免受莱姆病的亚单位疫苗。
The lipoprotein OspA is produced by the Lyme disease spirochetes primarily in unfed ticks. OspA production is down-regulated by the blood meal and it is not produced in mammals except for possible transient production during late stage infection in patients with Lyme arthritis. Vaccination with OspA elicits antibody (Ab) that can target spirochetes in the tick midgut during feeding and inhibit transmission to mammals. OspA was the primary component of the human LYMErix™ vaccine. LYMErix™ was available from 1998 to 2002 but then pulled from the market due to declining sales as a result of unsubstantiated concerns about vaccination induced adverse events and poor efficacy. It was postulated that a segment of OspA that shares sequence similarity with a region in human LFA-1 and may trigger putative autoimmune events. While evidence supporting such a link has not been demonstrated, most efforts to move forward with OspA as a vaccine component have sought to eliminate this region of concern. Here we identify an OspA linear epitope localized within OspA amino acid residues 221–240 (OspA221–240) that lacks the OspA region suggested to elicit autoimmunity. A peptide consisting of residues 221–240 was immunogenic in mice. Ab raised against OspA221–240 peptide surface labeled B. burgdorferi in IFAs and displayed potent Ab mediated-complement dependent bactericidal activity. BLAST analyses identified several variants of OspA221–240 and a closely related sequence in OspB. It is our hypothesis that integration of the OspA221–240 epitope into a multivalent-OspC based chimeric epitope based vaccine antigen (chimeritope) could result in a subunit vaccine that protects against Lyme disease through synergistic mechanisms.
登录
查看更多内容
DOI：
10.1073/pnas.90.9.4092
发表时间：
1993-05-01
影响因子：
11.1
作者：
FIKRIG, E;TAO, H;FLAVELL, RA
通讯作者：
FLAVELL, RA
影响因子：
9.4
作者：
Lagal, V;Postic, D;Baranton, G
通讯作者：
Baranton, G
影响因子：
2.1
作者：
Kiss, Timea;Cadar, Daniel;Spinu, Marina
通讯作者：
Spinu, Marina
影响因子：
3.1
作者：
Bockenstedt, LK;Hodzic, E;Barthold, SW
通讯作者：
Barthold, SW
影响因子：
2.6
作者：
Funk RA;Pleasant RS;Witonsky SG;Reeder DS;Werre SR;Hodgson DR
通讯作者：
Hodgson DR