Aberle Judith H, Aberle Stephan W, Kofler Regina M, Mandl Christian W
Institute of Virology, Kinderspitalgasse 15, A-1095 Vienna, Austria.
J Virol. 2005 Dec;79(24):15107-13. doi: 10.1128/JVI.79.24.15107-15113.2005.
A new vaccination principle against flaviviruses, based on a tick-borne encephalitis virus (TBEV) self-replicating noninfectious RNA vaccine that produces subviral particles, has recently been introduced (R. M. Kofler, J. H. Aberle, S. W. Aberle, S. L. Allison, F. X. Heinz, and C. W. Mandl, Proc. Natl. Acad. Sci. USA 7:1951-1956, 2004). In this study, we evaluated the potential of the self-replicating RNA vaccine in mice in comparison to those of live, attenuated vaccines and a formalin-inactivated whole-virus vaccine (ImmunInject). For this purpose, mice were immunized using gene gun-mediated application of the RNA vaccine and tested for CD8+ T-cell responses, long-term duration, neutralizing capacity, and isotype profile of specific antibodies and protection against lethal virus challenge. We demonstrate that the self-replicating RNA vaccine induced a broad-based, humoral and cellular (Th1 and CD8+ T-cell response) immune response comparable to that induced by live vaccines and that it protected mice from challenge. Even a single immunization with 1 microg of the replicon induced a long-lasting antibody response, characterized by high neutralizing antibody titers, which were sustained for at least 1 year. Nevertheless, it was possible to boost this response further by a second injection with the RNA vaccine, even in the presence of a concomitant CD8+ T-cell response. In this way it was possible to induce a balanced humoral and cellular immune response, similar to infection-induced immunity but without the safety hazards of infectious agents. The results also demonstrate the value of TBEV replicon RNA for inducing protective long-lasting antiviral responses.
最近引入了一种针对黄病毒的新型疫苗接种原理，该原理基于一种蜱传脑炎病毒（TBEV）自我复制的非感染性RNA疫苗，这种疫苗可产生亚病毒颗粒（R.M.科夫勒、J.H.阿伯勒、S.W.阿伯勒、S.L.艾利森、F.X.海因茨和C.W.曼德尔，《美国国家科学院院刊》7:1951 - 1956，2004年）。在本研究中，我们将自我复制RNA疫苗在小鼠体内的潜力与减毒活疫苗和福尔马林灭活全病毒疫苗（ImmunInject）进行了比较评估。为此，使用基因枪介导的方式对小鼠接种RNA疫苗，并检测其CD8 + T细胞反应、长期持续时间、中和能力、特异性抗体的亚型谱以及对致死性病毒攻击的保护作用。我们证明，自我复制RNA疫苗诱导了广泛的体液和细胞（Th1和CD8 + T细胞反应）免疫反应，与减毒活疫苗诱导的反应相当，并且能保护小鼠免受攻击。即使单次接种1微克复制子也能诱导持久的抗体反应，其特征是具有高中和抗体滴度，这种滴度至少维持1年。然而，即使在存在伴随的CD8 + T细胞反应的情况下，通过第二次注射RNA疫苗仍有可能进一步增强这种反应。通过这种方式，可以诱导出平衡的体液和细胞免疫反应，类似于感染诱导的免疫反应，但没有感染性病原体的安全隐患。结果还证明了TBEV复制子RNA在诱导保护性持久抗病毒反应方面的价值。
