Characterization of recombinant OspA in two different Borrelia vaccines with respect to immunological response and its relationship to functional parameters.
Characterization of recombinant OspA in two different Borrelia vaccines with respect to immunological response and its relationship to functional parameters.
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DOI：
10.1186/s12917-018-1625-7
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发表时间：
2018-10-16
影响因子：
2.6
通讯作者：
David F
中科院分区：
文献类型：
--
作者：
Grosenbaugh DA;De Luca K;Durand PY;Feilmeier B;DeWitt K;Sigoillot-Claude C;Sajous ML;Day MJ;David F
在北美，预防狗的莱姆病取决于有效的疫苗接种，以防止蜱虫传播的螺旋体伯氏疏螺旋体感染。大多数疫苗基于B的外表面脂蛋白A（OspA）的免疫，在蜱虫喂养期间有效预防螺旋体传播给犬。burgdorferi。最近，已经引入了含有另外的OspC蛋白部分的疫苗。这些被设计为通过在脊椎动物宿主内形成第二道防线来增强保护，其中OspC表达取代OspA作为主要表面抗原。然而，仍然缺乏证明OspC介导的保护作用的支持性数据。由于OspA免疫原性对于防止螺旋体传播至关重要;本研究旨在比较两种市售疫苗对伯氏疏螺旋体OspA的免疫原性。我们进一步表征了这些疫苗的OspA抗原组分的生化和生物物理特性。施用两组比格犬（n = 9）：（1）无佐剂/单价重组OspA疫苗（Recombitek® Lyme）或（2）有佐剂的重组OspA /OspC嵌合融合疫苗（Vanguard® crLyme）。由无佐剂/单价OspA疫苗引发的抗OspA抗体应答的开始显著早于二价OspA /OspC疫苗，并且在所有接种后时间点血清杀疏螺旋体活性显著更大。正如预期的那样，只有接种二价OspA/OspC疫苗的犬产生了体液抗OspC应答。然而，该组中只有九分之三的狗有积极的反应。OspA疫苗结构的比较显示，无佐剂/单价疫苗中的OspA主要为脂化形式，以高分子量洗脱（SEC-HPLC），表明胶束形成。相反，发现OspA/OspC疫苗的OspA部分是非脂化的，并作为单体蛋白洗脱。我们假设，这些结构差异可能是无佐剂单价重组OspA疫苗在犬中上级免疫原性优于OspA/OspC疫苗的含佐剂OspA组分的原因。
Prevention of Lyme disease in dogs in North America depends on effective vaccination against infection by the tick vector-born spirochete Borrelia burgdorferi. Most vaccines effectively prevent spirochete transmission to dogs during tick feeding based on immunization with the outer-surface lipoprotein A (OspA) of B. burgdorferi. More recently, vaccines containing additional OspC protein moieties have been introduced. These are designed to enhance protection by forming a second line of defense within the vertebrate host, where OspC expression replaces OspA as the dominant surface antigen. However, supportive data for demonstration of OspC mediated protection is still lacking. Since OspA immunogenicity is of paramount importance to protection against spirochete transmission; this study was designed to compare the immunogenicity of two commercially available vaccines against the Borrelia burgdorferi OspA. We further characterized OspA antigen fractions of these vaccines with respect to their biochemical and biophysical properties. Two groups of beagle dogs (n = 9) were administered either: (1) a nonadjuvanted/monovalent, recombinant OspA vaccine (Recombitek® Lyme) or (2) an adjuvanted, recombinant OspA /OspC chimeric fusion vaccine (Vanguard® crLyme). The onset of the anti-OspA antibody response elicited by the nonadjuvanted/monovalent OspA vaccine was significantly earlier than that for the bivalent OspA /OspC vaccine and serum borreliacidal activity was significantly greater at all post-vaccination time points. As expected, only dogs inoculated with the bivalent OspA/OspC vaccine mounted a humoral anti-OspC response. However, only three out of nine dogs in that group had a positive response. Comparison of the OspA vaccine structures revealed that the OspA in the nonadjuvanted/monovalent vaccine was primarily in the lipidated form, eluting (SEC-HPLC) at a high molecular weight, suggestive of micelle formation. Conversely, the OspA moiety of the OspA/OspC vaccine was found to be nonlipidated and eluted as the monomeric protein. We hypothesize that these structural differences may account for the superior immunogenicity of the nonadjuvanted monovalent recombinant OspA vaccine in dogs over the adjuvanted OspA fraction of the OspA/OspC vaccine.
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影响因子：
--
作者：
Baum, Elisabeth;Grosenbaugh, Deborah A.;Barbour, Alan G.
通讯作者：
Barbour, Alan G.
影响因子：
6.4
作者：
Rousselle, JC;Callister, SM;Wieneke, CA
通讯作者：
Wieneke, CA
影响因子：
--
作者：
LaFleur, Rhonda L.;Dant, Jennifer C.;Schell, Ronald F.
通讯作者：
Schell, Ronald F.
影响因子：
5.5
作者：
Toepfer, Katharina H.;Straubinger, Reinhard K.
通讯作者：
Straubinger, Reinhard K.
基于阳离子胶束的疫苗通过增强抗原摄取和生发中心的形成诱导有效的体液免疫反应
影响因子：
5.8
作者：
Luo, Zichao;Shi, Shuai;Li, Xingyi
通讯作者：
Li, Xingyi