Thomson S A, Sherritt M A, Medveczky J, Elliott S L, Moss D J, Fernando G J, Brown L E, Suhrbier A
The Cooperative Research Centre for Vaccine Technology, Queensland Institute of Medical Research, Brisbane, Australia.
J Immunol. 1998 Feb 15;160(4):1717-23.
Development of CD8 alphabeta CTL epitope-based vaccines requires an effective strategy capable of co-delivering large numbers of CTL epitopes. Here we describe a DNA plasmid encoding a polyepitope or "polytope" protein, which contained multiple contiguous minimal murine CTL epitopes. Mice vaccinated with this plasmid made MHC-restricted CTL responses to each of the epitopes, and protective CTL were demonstrated in recombinant vaccinia virus, influenza virus, and tumor challenge models. CTL responses generated by polytope DNA plasmid vaccination lasted for 1 yr, could be enhanced by co-delivering a gene for granulocyte-macrophage CSF, and appeared to be induced in the absence of CD4 T cell-mediated help. The ability to deliver large numbers of CTL epitopes using relatively small polytope constructs and DNA vaccination technology should find application in the design of human epitope-based CTL vaccines, in particular in vaccines against EBV, HIV, and certain cancers.
基于CD8αβ细胞毒性T淋巴细胞（CTL）表位的疫苗开发需要一种能够共同递送大量CTL表位的有效策略。在此，我们描述了一种编码多表位或“多聚表位”蛋白的DNA质粒，该蛋白包含多个连续的最小化小鼠CTL表位。用该质粒接种的小鼠对每个表位产生了MHC限制的CTL反应，并且在重组痘苗病毒、流感病毒和肿瘤攻击模型中证实了保护性CTL的存在。多聚表位DNA质粒接种产生的CTL反应持续了1年，可以通过共同递送粒细胞巨噬细胞集落刺激因子（GM-CSF）基因来增强，并且似乎是在没有CD4 T细胞介导的辅助的情况下诱导产生的。利用相对较小的多聚表位构建体和DNA接种技术递送大量CTL表位的能力，应该会在基于人类表位的CTL疫苗设计中得到应用，特别是在针对EB病毒、HIV和某些癌症的疫苗中。
