Pasetti M F, Anderson R J, Noriega F R, Levine M M, Sztein M B
Department of Pediatrics, University of Maryland, School of Medicine, Baltimore, Maryland 21201, USA.
Clin Immunol. 1999 Jul;92(1):76-89. doi: 10.1006/clim.1999.4733.
Attenuated Salmonella typhi strain CVD 915, harboring a deletion in guaBA that interrupts the biosynthesis of guanine nucleotides, was evaluated as a live vector vaccine for delivering foreign antigens utilizing prokaryotic or eukaryotic expression systems. Plasmids pTETnir15 and pcDNA3tetC encoding fragment C (Frag C) of tetanus toxin under the control of prokaryotic or eukaryotic promoters, respectively, were introduced into CVD 915 and administered intranasally to mice. Purified pcDNA3tetC and Frag C were given intramuscularly. High titers of serum IgG1, IgG2a, and IgG2b antibodies against Frag C were elicited by CVD 915(pTETnir15) and CVD 915(pcDNA3tetC). These responses were significantly higher than those induced by pcDNA3tetC. Proliferative responses and IL-2 and IFN-gamma production were observed in splenocytes exposed to S. typhi antigens and Frag C. We conclude that CVD 915 is a highly efficient live vector to carry foreign genes under eukaryotic or prokaryotic control and elicit potent immune responses.
携带guaBA缺失从而中断鸟嘌呤核苷酸生物合成的减毒伤寒沙门氏菌菌株CVD 915，被评估作为一种活载体疫苗，用于利用原核或真核表达系统递送外源抗原。分别在原核或真核启动子控制下编码破伤风毒素片段C（Frag C）的质粒pTETnir15和pcDNA3tetC被导入CVD 915，并经鼻内给予小鼠。纯化的pcDNA3tetC和Frag C通过肌肉内注射给予。CVD 915(pTETnir15)和CVD 915(pcDNA3tetC)诱导产生了高滴度的针对Frag C的血清IgG1、IgG2a和IgG2b抗体。这些反应显著高于pcDNA3tetC诱导的反应。在暴露于伤寒沙门氏菌抗原和Frag C的脾细胞中观察到增殖反应以及IL-2和IFN-γ的产生。我们得出结论，CVD 915是一种高效的活载体，可在真核或原核控制下携带外源基因并引发强烈的免疫反应。
