Immunogenicity of latency-associated antigens of Mycobacterium tuberculosis in DNA-vaccinated mice

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), persists within infected macrophages for long periods of time in a metabolically inactive but reversible state known as dormancy. Since the majority of adult pulmonary TB is caused by the reactivation of persistent Mtb, novel vaccines to protect against disease reactivation and novel biomarkers to provide the basis of new diagnosis of latent infection are urgently needed. To meet this demand, we assessed the immunogenicity of 32 latency-associated proteins in DNA-vaccinated mice. By using a Helios gene gun, BALB/c and C57BL/6 mice were vaccinated with plasmids carrying DNAs for latency-associated antigens encoded by the DosR regulon. Of the 32 antigens tested, 12 induced antigen-specific T-cell responses in vaccinated BALB/c mice and 9 induced responses in C57BL/6 mice. Five antigens (Rv1998c, Rv2031c, Rv2032, Rv2623, and Rv3132c) induced T-cell responses in both mice strains. In addition, at least 12 and 3 antigens induced antigen-specific antibody production in vaccinated BALB/c and C57BL/6 mice, respectively. Of these, 3 antigens (Rv2029c, Rv2626c, and Rv3132c) induced strong antibody production in both mice strains. These results might be applicable for the future development of a novel vaccine and biomarkers for latent TB infection, although further analyses in human blood samples are necessary.