Allsopp C E, Plebanski M, Gilbert S, Sinden R E, Harris S, Frankel G, Dougan G, Hioe C, Nixon D, Paoletti E, Layton G, Hill A V
Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, GB.
Eur J Immunol. 1996 Aug;26(8):1951-9. doi: 10.1002/eji.1830260841.
A variety of vaccine delivery systems including peptides with various adjuvants, recombinant particles, live recombinant viruses and bacteria and plasmid DNA were tested for their ability to induce CD8+ cytotoxic T lymphocytes (CTL) against a well-defined epitope (amino acids 252-260) from the circumsporozoite (CS) protein of Plasmodium berghei. We compared routes of immunization that would be applicable for the administration of a malaria vaccine in humans. The majority of these vaccines did not induce high CTL responses in the spleens of immunized mice. However, both a yeast-derived Ty virus-like particle expressing the optimal nine-amino acid epitope SYIPSAEKI from the CS protein (CSP-VLP) and a lipid-tailed peptide of this same sequence induced high levels of the major histocompatibility complex (MHC) class I-restricted CTL with one and three subcutaneous immunizations, respectively. Moreover, these CTL were able to recognize naturally processed antigen expressed by a recombinant vaccinia virus. The levels of CTL induced by CSP-VLP could be augmented by co-immunization with certain cytokines. Target cells pulsed with CSP-VLP were recognized and lysed, showing that the particles were effectively processed and presented through MHC class I presentation pathway. The levels of CTL induced using CSP-VLP and lipopeptides are comparable to those observed after immunization with multiple doses of irradiated sporozoites.
测试了多种疫苗递送系统，包括与各种佐剂结合的肽、重组颗粒、活重组病毒和细菌以及质粒DNA，以评估它们诱导针对来自伯氏疟原虫环子孢子（CS）蛋白的明确表位（氨基酸252 - 260）的CD8 + 细胞毒性T淋巴细胞（CTL）的能力。我们比较了适用于人类疟疾疫苗接种的免疫途径。这些疫苗中的大多数在免疫小鼠的脾脏中并未诱导出高CTL反应。然而，一种表达来自CS蛋白的最佳九氨基酸表位SYIPSAEKI的酵母衍生Ty病毒样颗粒（CSP - VLP）和该相同序列的脂尾肽，分别通过一次和三次皮下免疫诱导出高水平的主要组织相容性复合体（MHC）I类限制性CTL。此外，这些CTL能够识别由重组痘苗病毒表达的天然加工抗原。通过与某些细胞因子共同免疫，可以增强CSP - VLP诱导的CTL水平。用CSP - VLP脉冲的靶细胞被识别并裂解，表明这些颗粒通过MHC I类呈递途径被有效加工和呈递。使用CSP - VLP和脂肽诱导的CTL水平与多次接种辐照子孢子后观察到的水平相当。
