Kwissa Marcin, Lindblad Erik B, Schirmbeck Reinhold, Reimann Joerg
Institute for Medical Microbiology, University of Ulm, Albert Einstein Allee 11, 89081 Ulm, Germany.
J Mol Med (Berl). 2003 Aug;81(8):502-10. doi: 10.1007/s00109-003-0452-9. Epub 2003 Jul 16.
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.
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。