Study on anti-tuburculosis DNA vaccines using attenuated Listeria strain as the carrier

在这项研究中，我们表明，诱导特异性保护性细胞免疫结核分枝杆菌接种重组减毒单核细胞增生李斯特菌菌株。我们构建了自毁衰减L。携带Ag 85复合物真核表达质粒的单核细胞增多症Δ2菌株这些重组菌感染小鼠J774A.1细胞后，可诱导小鼠产生PPD特异性细胞免疫反应，如足垫反应、足垫反应、足垫反应等。脾细胞的增殖反应和脾细胞产生干扰素-γ，表明用这些重组L.携带Ag 85家族分子的真核表达质粒的单核细胞增多症。此外，静脉接种这些重组细菌携带表达质粒的Ag 85 A，Ag 85 B，或MPB/MPT 51到BALB/c小鼠引起显着的保护性反应，这些诱发的活卡介苗。值得注意的是，这是第一份显示MPB/MPT 51是一种主要的保护性抗原以及据报道是主要的分枝杆菌保护性抗原的Ag 85 A和Ag 85 B的报告。

In this study, we showed the induction of specific protective cellular immunity against Mycobacterium tuberculosis employing vaccination with recombinant attenuated Listeria monocytogenes strains. We constructed self-destructing attenuated L. monocytogenes Δ2 strains carrying eukaryotic expression plasmids for Ag85 complex (Ag85A and Ag85B) and MPB/MPT51 molecules.Infection of these recombinant bacteria allowed expression of the genes in J774A.1 murine macrophage cell line.The intraperitoneal vaccination of C57BL/6 mice with these recombinant bacteria was capable of inducing purified protein derivative (PPD)-speciflc cellular immunities such as footpad reaction, proliferative responses of splenocytes and interferon-γ production from splenocyles, suggesting the efficacy of the vaccination against mycobacterial infection with these recombinant L. monocytogenes carrying eukaryotic expression plasmids for Ag85 family molecules. Furthermore, intravenous vaccination of these recombinant bacteria carrying expression plasmids for Ag85A, Ag85B, or MPB/MPT51 into BALB/c mice elicited significant protective responses comparable to those evoked by live BCG vaccine. Of note, it is the first report showing MPB/MPT51 is a major protective Ag as well as Ag85A and Ag85B, which have been reported to be major mycobacterial protective Ags.