Oldstone M B, Tishon A, Eddleston M, de la Torre J C, McKee T, Whitton J L
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037.
J Virol. 1993 Jul;67(7):4372-8. doi: 10.1128/JVI.67.7.4372-4378.1993.
Persistent virus infections are increasingly being recognized as a significant cause of human morbidity and mortality. To establish persistence, a virus must establish infection and evade eradication by the host immune response, in particular by cytotoxic T lymphocytes (CTL). We have studied a virus that establishes persistence in part by suppressing the CTL response of the infected host. The virus persists in many cell types, including lymphocytes and macrophages. We show that prior immunization with a vaccine designed to induce CTL (in the absence of antiviral antibody) confers complete protection against subsequent establishment of persistence in all tissues analyzed. The vaccine can be designed to express as few as 10 amino acids of a viral protein that comprise the CTL epitope. Further, two CTL epitopes for two discrete MHC haplotypes can be successfully used in a single vaccine that protects both strains of mice. Hence, a "string of CTL epitopes" (beads) concept for vaccination is feasible. Finally, the CTL vaccine provided protection against the establishment of persistence by an immunosuppressive virus.
持续性病毒感染日益被认为是导致人类发病和死亡的重要原因。为了建立持续性感染，病毒必须建立感染并逃避宿主免疫反应的清除，特别是细胞毒性T淋巴细胞（CTL）的清除。我们研究了一种病毒，它部分通过抑制受感染宿主的CTL反应来建立持续性感染。这种病毒在许多细胞类型中持续存在，包括淋巴细胞和巨噬细胞。我们表明，预先用旨在诱导CTL（在没有抗病毒抗体的情况下）的疫苗进行免疫接种，可对随后在所有分析的组织中建立持续性感染提供完全保护。该疫苗可以设计成表达仅包含CTL表位的病毒蛋白的10个氨基酸。此外，针对两种不同MHC单倍型的两个CTL表位可以成功地用于一种保护两种小鼠品系的单一疫苗中。因此，“一串CTL表位”（珠子）的疫苗接种概念是可行的。最后，CTL疫苗对免疫抑制病毒建立持续性感染提供了保护。
