Immunogenicity of 60 novel latency-related antigens of Mycobacterium tuberculosis

Abstract

The aim of our work here was to evaluate the immunogenicity of 60 mycobacterial antigens, some of which have not been previously assessed, notably a novel series of in vivo-expressed Mycobacterium tuberculosis (IVE-TB) antigens. We enrolled 505 subjects and separated them in individuals with and without latent tuberculosis infection (LTBI) vs. patients with active tuberculosis (TB). Following an overnight and 7 days stimulation of whole blood with purified recombinant M. tuberculosis antigens, interferon-γ (IFN-γ) levels were determined by ELISA. Several antigens could statistically significantly differentiate the groups of individuals. We obtained promising antigens from all studied antigen groups [dormancy survival regulon (DosR regulon) encoded antigens; resuscitation-promoting factors (Rpf) antigens; IVE-TB antigens; reactivation associated antigens]. Rv1733, which is a probable conserved transmembrane protein encoded in DosR regulon, turned out to be very immunogenic and able to discriminate between the three defined TB status, thus considered a candidate biomarker. Rv2389 and Rv2435n, belonging to Rpf family and IVE-TB group of antigens, respectively, also stood out as LTBI biomarkers. Although more studies are needed to support our findings, the combined use of these antigens would be an interesting approach to TB immunodiagnosis candidates.

New Genome-Wide Algorithm Identifies Novel In-Vivo Expressed Mycobacterium Tuberculosis Antigens Inducing Human T-Cell Responses with Classical and Unconventional Cytokine Profiles

“…For comparative purposes we also included ten additional Mtb antigens identified previously (Rv0867, Rv1009, Rv1733, Rv1737, Rv2029, Rv2032, Rv2034, Rv2389, Rv2450, and Rv3353)2324414748495051525354. Diluted whole blood samples were stimulated for six days and the cytokine levels were assessed by a seven-plex assay (data shown only for IFN-γ, IL-17, TNF-α and IP-10 Fig.…”

Proteomic analysis of protein purified derivative of Mycobacterium bovis

“…Fourteen of them belong to a novel series of in vivo expressed M. tuberculosis (IVE-TB) T cell antigens [31, 32]. Two reactivation associated antigens, namely Mb0391c (gene name: clpB) and Mb2492c (gene name: rplB) and three lipoprotein T cell antigens, namely Mb0959 (gene name: pstS1), Mb0956c (gene name: pstS2) and Mb0951 (gene name: pstS3), known to generate very high levels of cytokine secretion [33], were also detected.…”

Mycobacterium Tuberculosis Virulence: Insights and Impact on Vaccine Development

“…Taken together these data indicate that the antigen repertoire expressed by M. tuberculosis changes over time and space. Beyond the antigens preferentially expressed during active growth, the other set of antigens are those included in the DosR and EHR [55,60], those induced by starvation [63] and those induced during reactivation [64,65]. This antigen variability during infection poses a serious problem in the design of a vaccine able to target the bacteria during the whole course of infection [66,67].…”