Effective induction of HIV-specific CTL by multi-epitope using gene gun in a combined vaccination regime
Effective induction of HIV-specific CTL by multi-epitope using gene gun in a combined vaccination regime
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DOI：
10.1016/s0264-410x(98)00238-2
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发表时间：
1999-02-12
期刊：
影响因子：
5.5
通讯作者：
McMichael, A
中科院分区：
文献类型：
--
作者：
Hanke, T;Neumann, VC;McMichael, A
可靠有效地诱导细胞毒性 T 淋巴细胞 (CTL) 是疫苗研究的主要目标之一。此前，新型 HIV 候选疫苗被构建为使用 DNA 载体传递的一系列 CTL 表位（20 只人类、3 只猕猴和 1 只小鼠）[Hanke T、Schneider J、Gilbert SG、Hill AVS、McMichael A。 HIV 和恶性疟原虫的 DNA 多 CTL 表位疫苗：小鼠的免疫原性。疫苗 1998;16:426-435.] 或改良痘苗安卡拉 (MVA [Hanke T, Blanchard TJ, Schneider J, Ogg GS, Tan R, Becker MSG, Gilbert SG, Hill AVS, Smith GL, McMichael A. 基于 MVA 的多 CTL 表位疫苗静脉内和肌肉内注射的免疫原性 老鼠。 J Gen Virol 1998；79：83-90.]），即可接受用于人类的疫苗载体。在小鼠中，单独肌内（i.m.）针注射任一疫苗均引发良好的 CTL 反应。这里，证明当使用Accell 基因枪皮内递送时，多表位DNA也诱导CTL。重新免疫后和三次分娩后 CTL 反应增加，与单次肌内注射诱导的反应相当。注射。最近的证据表明，结合途径和疫苗载体可以增强疫苗递送或编码抗原的免疫原性。此处，显示通过肌内引发/基因枪加强施用DNA比基因枪引发/肌内注射更有效地诱导CTL。助推。通过使用基因枪递送 DNA 和重组 MVA 进行连续疫苗接种，获得了类似的增量。因此，特定的路线或疫苗载体序列而不是单一疫苗的简单初免-加强递送对于有效引发 CTL 至关重要。 (C) 1999 Elsevier Science Ltd. 保留所有权利。
Reliable and effective induction of cytotoxic T-lymphocytes (CTL) is one of the prime objectives of vaccine research. Previously, novel HIV vaccine candidates were constructed as a string of CTL epitopes (20 human, 3 macaque and 1 mouse) delivered using a DNA vector [Hanke T, Schneider J, Gilbert SG, Hill AVS, McMichael A. DNA multi-CTL epitope vaccines for HIV and Plasmodium falciparum: immunogenicity in mice. Vaccine 1998;16:426-435.] or modified vaccinia Ankara (MVA [Hanke T, Blanchard TJ, Schneider J, Ogg GS, Tan R, Becker MSG, Gilbert SG, Hill AVS, Smith GL, McMichael A. Immunogenicities of intravenous and intramuscular administrations of MVA-based multi-CTL epitope vaccine for HIV in mice. J Gen Virol 1998;79:83-90.]), i.e. vaccine vehicles acceptable for use in humans, In mice, a single intramuscular (i.m.) needle injection of either vaccine alone elicited good CTL responses. Here, it is demonstrated that the multi-epitope DNA also induced CTL when delivered intradermally using the Accell(R): gene gun. The CTL responses increased after re-immunization and after three deliveries were comparable to those induced by a single i.m. injection. Recent evidence indicates that combining routes and vaccine vehicles enhances the immunogenicity of vaccine-delivered or -encoded antigens. Here, it is shown that administration of DNA by an i.m, priming/gene gun boosting more efficiently induced CTL than gene gun pr iming/i.m. boosting. A similar increment was obtained by sequential vaccinations using a gene gun-delivered DNA followed by recombinant MVA. Thus particular sequences of routes or vaccine vehicles rather than simple prime-boost delivery of a single vaccine is critical for an effective elicitation of CTL. (C) 1999 Elsevier Science Ltd. All rights reserved.