Adenylate kinase: a novel antigen for immunodiagnosis and subunit vaccine against tuberculosis

Mycobacterium tuberculosis (M.tb)-derived antigens capable of inducing strong cellular and/or humoral responses are potential targets for both immunodiagnosis and vaccine development against tuberculosis (TB). In the present study, we identified adenylate kinase (ADK, Rv0733) as an antigen that induces high cellular and antibody responses in active TB patients. We consequently tested the use of ADK-specific T cells and antibodies as biomarkers for TB diagnosis. The ADK-specific IFN-γ-producing cells detected by ELISPOT assay showed a sensitivity of 85.0 % and specificity of 94.15 % for TB diagnosis while ADK-specific IgG antibody showed a sensitivity of 40.35 % and specificity of 96.43 %. Combining ADK-specific cellular and antibody responses increased the sensitivity to 91.59 % and the specificity to 96.15 %. Immunogenicity and protection against M.tb infection were further tested in a murine model. Immunization with ADK protein elicited strong specific T- and B-cell responses, and provided protection against the virulent H37Rv stain of M.tb resulting in lower bacilli load in the spleens and lungs. More ADK-specific polyfunctional Th1 cells were observed in the lungs when compared to adjuvant-immunized mice. ADK thus may serve as a novel M.tb antigen for TB immunodiagnosis and development of subunit vaccines.

ADK induces strong immune responses both in humans and mice. ADK-specific IFN-γ production and B-cell responses have high potential for TB diagnosis. ADK immunization provides protection against M.tb infection.