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将DNA疫苗和蛋白质疫苗与磷酸铝共同递送可刺激产生强效且多价的免疫反应。

Codelivery of a DNA vaccine and a protein vaccine with aluminum phosphate stimulates a potent and multivalent immune response.

作者信息

Kwissa Marcin, Lindblad Erik B, Schirmbeck Reinhold, Reimann Joerg

机构信息

Institute for Medical Microbiology, University of Ulm, Albert Einstein Allee 11, 89081 Ulm, Germany.

出版信息

J Mol Med (Berl). 2003 Aug;81(8):502-10. doi: 10.1007/s00109-003-0452-9. Epub 2003 Jul 16.

Abstract

The study explores the possibility of efficiently codelivering DNA vaccines and protein-based vaccines by formulation with aluminum phosphate (AlPO4). When mixed with aluminum adjuvants, plasmid DNA bound tightly onto aluminum hydroxide [Al(OH)3] but not to AlPO4. Different doses of DNA vaccines formulated with AlPO4 [but not Al(OH)3] induced enhanced humoral responses and supported priming of MHC class I restricted cellular immunity. Different proteins mixed with the plasmid DNA vaccine in the AlPO4 formulation did not impair its immunogenicity. Coinjection of two different vaccine-relevant antigens in the same AlPO4 formulation, one as a DNA vaccine and the other as a recombinant protein, elicited polyvalent, humoral, and cellular immune responses to all antigens delivered. The isotype profiles of the induced humoral responses and the cytokine profiles of the specifically primed T cell responses indicated that the combined vaccines supported copriming of Th1- and Th2-biased as well as balanced responses. These findings indicate that the AlPO4 adjuvant, a widely accepted adjuvant in human vaccination practice, can be used to combine protein- and DNA-based vaccination to prime an enhanced and balanced specific immunity.

摘要

本研究探讨了通过与磷酸铝(AlPO4)制剂联合使用来高效共递送DNA疫苗和基于蛋白质的疫苗的可能性。当与铝佐剂混合时,质粒DNA紧密结合在氢氧化铝[Al(OH)3]上,但不与AlPO4结合。用AlPO4(而非Al(OH)3)配制的不同剂量的DNA疫苗可诱导增强的体液反应,并支持MHC I类限制性细胞免疫的启动。与AlPO4制剂中的质粒DNA疫苗混合的不同蛋白质不会损害其免疫原性。在同一AlPO4制剂中同时注射两种不同的与疫苗相关的抗原,一种作为DNA疫苗,另一种作为重组蛋白,可引发对所有递送抗原的多价、体液和细胞免疫反应。诱导的体液反应的同种型谱和特异性启动的T细胞反应的细胞因子谱表明,联合疫苗支持Th1和Th2偏向以及平衡反应的共启动。这些发现表明,AlPO4佐剂作为人类疫苗接种实践中广泛接受的佐剂,可用于联合基于蛋白质和DNA的疫苗接种,以启动增强且平衡的特异性免疫。

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