A novel method for enhancement of peptide vaccination utilizing T-cell epitopes from conventional vaccines.
A novel method for enhancement of peptide vaccination utilizing T-cell epitopes from conventional vaccines.
复制标题
DOI：
10.1016/j.vaccine.2012.12.083
复制
发表时间：
2013-03
期刊：
影响因子：
5.5
通讯作者：
A. Yano;Yoshikatsu Miwa;Yoshito Kanazawa;Kaori Ito;M. Makino;S. Imai;N. Hanada;T. Nisizawa
中科院分区：
文献类型：
--
作者：
A. Yano;Yoshikatsu Miwa;Yoshito Kanazawa;Kaori Ito;M. Makino;S. Imai;N. Hanada;T. Nisizawa
多肽疫苗有两个基本缺点，即抗原性低和MHC限制。在我们之前的研究中，我们提出了疫苗多肽的设计来克服这些缺点。疫苗按N-末端、精氨酸-甘氨酸-天冬氨酸(RGD)、T细胞表位多肽、二赖氨酸连接物(KK)和B细胞表位多肽的顺序构建。虽然疫苗多肽基本上可以在没有免疫佐剂的情况下通过腹腔、皮下和鼻腔给药诱导针对宿主的B细胞表位多肽特异性抗体，但一些多肽抗原需要佐剂才能诱导产生抗体。在这项研究中，我们提出了一种新的方案，利用宿主对传统类毒素疫苗的免疫反应，即淋巴细胞对T细胞表位多肽的活性来增强多肽的免疫原性。我们从白喉类毒素(一种常规疫苗抗原)和部分淀粉样β蛋白(A-β)中选择了多表位类型的T细胞表位作为B细胞表位。在多肽免疫前接种常规类毒素疫苗。利用该方案，我们成功地增强了C57BL/6和BALB/c小鼠鼻腔免疫诱导的抗Aβ抗体。此外，疫苗多肽诱导从健康志愿者身上收集的外周血淋巴细胞向白喉类毒素转化。这些结果表明，采用新方案的多肽疫苗将为抗体诱导提供一种有效的方法。
Peptide vaccines have two fundamental weak points, namely low antigenicity and MHC-restriction. In our previous study, we proposed the design of vaccine peptide to overcome these weakpoints. The vaccine was constructed in the following order, N-terminal, Arg-Gly-Asp (RGD), T-cell epitope peptide, di-lysine linker (KK) to B-cell epitope peptide. Although the vaccine peptide can basically induce B-cell epitope peptide specific antibodies to the host without immune adjuvants via intraperitoneal, subcutaneous and intranasal administration, some peptide antigens require adjuvants for antibody induction. In this study, we propose a novel protocol to enhance the immunogenicity of the peptide utilizing the host immune response to a conventional toxoid vaccine, which are lymphocyte activities to the T-cell epitope peptide. We selected multiagretope-type T-cell epitopes from diphtheria toxoid, a conventional vaccine antigen, and a part of amyloid-beta peptide (Aβ) as a B-cell epitope. The conventional toxoid vaccine was immunized before the peptide immunization. Using this protocol, we succeeded in the enhancement of the anti-Aβ antibodies induction by intranasal immunization without any immune adjuvants in C57BL/6 and Balb/c mice. Furthermore, the vaccine peptide induced the transformation of peripheral blood lymphocytes collected from healthy volunteers carrying immunities to diphtheria toxoid. These results suggested that our peptide vaccines with the novel protocol would provide an effective method for antibody induction.