Bruce Christine B, Akrigg Alan, Sharpe Sally A, Hanke Tomáš, Wilkinson Gavin W G, Cranage Martin P
Centre for Applied Microbiology and Research, Porton Down, Salisbury SP4 0JG, UK1.
Institute of Molecular Medicine, University of Oxford, The John Radcliffe Hospital, Headley Way, Oxford OX3 9DS, UK 2.
J Gen Virol. 1999 Oct;80 ( Pt 10):2621-2628. doi: 10.1099/0022-1317-80-10-2621.
An effective vaccine against infection with human immunodeficiency virus type 1 (HIV-1) is thought likely to require both a humoral and a CTL immune response. A non-replicating adenovirus vector system has been developed that can induce both a humoral and CTL response to HIV-1 envelope in mice. It is demonstrated that the stimulatory tat/rev 5' splice-donor site sequence is required for efficient expression of HIV-1 env by this adenovirus vector system. rev can be provided bicistronically or in trans to result in good expression of env in vitro. A humoral immune response was detected after two immunizations with a bicistronic recombinant adenovirus (RAd142). The response was dose dependent, 5x10(7) p.f.u. inducing a response in some, but not all, animals and 1x10(8) p.f.u. giving a consistent antibody response. However, CTLs were induced by the lower dose of virus and after only one immunization with the higher dose. A positive CTL response was also seen consistently when the two monocistronic adenoviruses (RAd501 expressing env and RAd46 expressing rev) were given together, although two immunizations were required to give approximately the same level of response as seen with the bicistronic virus. RAd501 on its own also gave a low CTL response when two immunizations were given. It is suggested that a lower level of env expression is required to produce a CTL response than a humoral response and that this nonreplicating adenovirus vector is a good system for inducing CTL.
一种有效的抗1型人类免疫缺陷病毒（HIV-1）感染疫苗可能需要体液免疫和细胞毒性T淋巴细胞（CTL）免疫反应。已经开发出一种非复制型腺病毒载体系统，该系统可在小鼠体内诱导针对HIV-1包膜的体液免疫和CTL反应。结果表明，这种腺病毒载体系统高效表达HIV-1 env需要刺激性的tat/rev 5'剪接供体位点序列。rev可以通过双顺反子方式提供或反式提供，从而在体外实现env的良好表达。用双顺反子重组腺病毒（RAd142）进行两次免疫后检测到体液免疫反应。该反应呈剂量依赖性，5×10⁷ 噬斑形成单位（p.f.u.）可在部分而非全部动物中诱导反应，而1×10⁸ p.f.u.可产生一致的抗体反应。然而，较低剂量的病毒可诱导CTL产生，且高剂量仅免疫一次后即可诱导CTL产生。当同时给予两种单顺反子腺病毒（表达env的RAd501和表达rev的RAd46）时，也始终能观察到阳性CTL反应，不过需要两次免疫才能产生与双顺反子病毒大致相同水平的反应。单独使用RAd501进行两次免疫时也会产生较低的CTL反应。研究表明，产生CTL反应所需的env表达水平低于产生体液免疫反应所需的水平，并且这种非复制型腺病毒载体是诱导CTL的良好系统。
