Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Vaccine. 2013 Oct 1;31(42):4795-801. doi: 10.1016/j.vaccine.2013.07.085. Epub 2013 Aug 12.
Helicobacter pylori neutrophil-activating protein (NAP) is a toll-like receptor 2 (TLR2) agonist and potent immunomodulator inducing Th1-type immune response. Here we present data about characterization of the humoral immune response against NAP-tagged antigens, encoded by attenuated measles virus (MV) vector platform, in MV infection susceptible type I interferon receptor knockout and human CD46 transgenic (Ifnarko-CD46Ge) mice. Immunogenicity of MV expressing a full-length human immunoglobulin lambda light chain (MV-lambda) was compared to that of MV expressing lambda-NAP chimeric protein (MV-lambda-NAP). MV-lambda-NAP immunized Ifnarko-CD46Ge mice developed significantly higher (6-20-fold) anti-lambda ELISA titers as compared to the MV-lambda-immunized control animal group, indicating that covalently-linked NAP co-expression significantly enhanced lambda immunogenicity. In contrast, ELISA titers against MV antigens were not significantly different between the animals vaccinated with MV-lambda or MV-lambda-NAP. NAP-tagged antigen expression did not affect development of protective anti-measles immunity. Both MV-lambda and MV-lambda-NAP-immunized groups showed strong virus neutralization serum titers in plaque reduction microneutralization test. These results demonstrated that MV-encoded lambda-NAP is highly immunogenic as compared to the unmodified full-length lambda chain. Boost of immune response to poor immunogens using live vectors expressing NAP-tagged chimeric antigens is an attractive approach with potential application in immunoprophylaxis of infectious diseases and cancer immunotherapy.
幽门螺杆菌中性粒细胞激活蛋白(NAP)是 Toll 样受体 2(TLR2)激动剂和有效的免疫调节剂,可诱导 Th1 型免疫反应。在此,我们介绍了关于减毒麻疹病毒(MV)载体平台编码的 NAP 标记抗原的体液免疫反应特征的数据,该载体在 MV 感染易感的 I 型干扰素受体敲除和人 CD46 转基因(Ifnarko-CD46Ge)小鼠中。比较了表达全长人免疫球蛋白 lambda 轻链的 MV(MV-lambda)与表达 lambda-NAP 嵌合蛋白的 MV(MV-lambda-NAP)的免疫原性。与接受 MV-lambda 免疫的对照动物组相比,接受 MV-lambda-NAP 免疫的 Ifnarko-CD46Ge 小鼠中针对 lambda 的 ELISA 滴度显著升高(6-20 倍),表明共价连接的 NAP 共表达显著增强了 lambda 的免疫原性。相比之下,接种 MV-lambda 或 MV-lambda-NAP 的动物之间针对 MV 抗原的 ELISA 滴度没有显着差异。NAP 标记抗原的表达不会影响保护性抗麻疹免疫的发展。在斑块减少微量中和试验中,接受 MV-lambda 或 MV-lambda-NAP 免疫的组均显示出强烈的病毒中和血清滴度。这些结果表明,与未修饰的全长 lambda 链相比,MV 编码的 lambda-NAP 具有更高的免疫原性。使用表达 NAP 标记嵌合抗原的活载体来增强对低免疫原性抗原的免疫反应是一种很有吸引力的方法,具有在传染病和癌症免疫治疗中的免疫预防中的潜在应用。