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

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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.