Humoral and cellular immune response to RNA immunization with flavivirus Replicons derived from tick-borne encephalitis virus
Humoral and cellular immune response to RNA immunization with flavivirus Replicons derived from tick-borne encephalitis virus
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DOI：
10.1128/jvi.79.24.15107-15113.2005
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发表时间：
2005-12-01
影响因子：
5.4
通讯作者：
Mandl, CW
中科院分区：
文献类型：
--
作者：
Aberle, JH;Aberle, SW;Mandl, CW
最近提出了一种新的针对黄病毒的疫苗原理，该原理基于壁虱传播的脑炎病毒(TBEV)自我复制的产生亚病毒颗粒的非传染性RNA疫苗(R.M.Kofler，J.H.Aberle，S.W.Aberle，S.L.Allison，F.X.Heinz和C.W.Mandl，Proc.)。娜塔莉。阿卡德。SCI。美国7：1951-1956,2004)。在这项研究中，我们评估了在小鼠身上自我复制的RNA疫苗的潜力，并与活的、减毒的疫苗和福尔马林灭活的全病毒疫苗(免疫注射)进行了比较。为此，用基因枪介导的RNA疫苗免疫小鼠，并测试CD8(+)T细胞反应、长期持续时间、中和能力、特定抗体的同型特征和对致死性病毒攻击的保护作用。我们证明，自我复制的RNA疫苗诱导了与活疫苗相似的广泛的、不道德的和细胞(Th1和CD8(+)T细胞反应)免疫反应，并保护小鼠免受攻击。即使是1毫克复制子的单次免疫，也会引起以高中和抗体效价为特征的长期抗体反应，并持续至少1年。然而，即使在伴随CD8(+)T细胞应答的情况下，通过第二次注射RNA疫苗也有可能进一步增强这种应答。通过这种方式，可以诱导一种平衡的不道德和细胞免疫反应，类似于感染诱导的免疫，但没有感染剂的安全危险。这些结果也证明了TBEV复制子RNA在诱导保护性长效抗病毒反应方面的价值。
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, Immoral 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 mu g 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 Immoral 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.