Peng S, Frazer I H, Fernando G J, Zhou J
Centre for Immunology and Cancer Research, University of Queensland, Princess Alexandra Hospital, Woolloongabba, Qld., Australia.
Virology. 1998 Jan 5;240(1):147-57. doi: 10.1006/viro.1997.8912.
To evaluate an antigen delivery system in which exogenous antigen can target the major histocompatibility complex (MHC) class I pathway, a single human papillomavirus (HPV) 16 E7 cytotoxic T lymphocyte (CTL) epitope and a single HIV gp160 CTL epitope were separately fused to the C-terminus of bovine papillomavirus 1 (BPV1) L1 sequence to form hybrid BPV1L1 VLPs. Mice immunized with these hybrid VLPs mounted strong CTL responses against the relevant target cells in the absence of any adjuvants. In addition, the CTL responses induced by immunization with BPV1L1/HPV16E7CTL VLPs protected mice against challenge with E7-transformed tumor cells. Furthermore, a high titer-specific antibody response against BPV1L1 VLPs was also induced, and this antiserum could inhibit papillomavirus-induced agglutination of mouse erythrocytes, suggesting that the antibody may recognize conformational determinates relevant to virus neutralization. These data demonstrate that hybrid BPV1L1 VLPs can be used as carriers to target antigenic epitopes to both the MHC class I and class II pathways, providing a promising strategy for the design of vaccines to prevent virus infection, with the potential to elicit therapeutic virus-specific CTL responses.
为了评估一种能使外源性抗原靶向主要组织相容性复合体（MHC）I类途径的抗原递送系统，将单个16型人乳头瘤病毒（HPV）E7细胞毒性T淋巴细胞（CTL）表位和单个HIV gp160 CTL表位分别与牛乳头瘤病毒1（BPV1）L1序列的C末端融合，以形成杂交BPV1L1病毒样颗粒（VLP）。用这些杂交VLP免疫的小鼠在没有任何佐剂的情况下对相关靶细胞产生了强烈的CTL反应。此外，用BPV1L1/HPV16E7CTL VLP免疫诱导的CTL反应保护小鼠免受E7转化肿瘤细胞的攻击。此外，还诱导了针对BPV1L1 VLP的高滴度特异性抗体反应，并且这种抗血清能够抑制乳头瘤病毒诱导的小鼠红细胞凝集，这表明该抗体可能识别与病毒中和相关的构象决定簇。这些数据表明，杂交BPV1L1 VLP可作为载体，将抗原表位靶向MHC I类和II类途径，为设计预防病毒感染的疫苗提供了一种有前景的策略，具有引发治疗性病毒特异性CTL反应的潜力。
