title: T cell recall response of two hypothetical proteins (Rv2251 and Rv2721c) from Mycobacterium tuberculosis in healthy household contacts of TB - Possible subunit vaccine candidates.
abstract: The demonstrated variable efficacy of the only licensed TB vaccine Mycobacterium bovis bacillus Calmette-Guérin (M. bovis BCG) encourages the need for new vaccine candidates against TB. Antigen specific cellular immune response is often considered imperative during Mycobacterium tuberculosis (M. tuberculosis) infection and antigens that are strongly associated with the latent phase of infection are drawing increasing attention for anti-TB vaccine development. Here, we investigated the phenotypic and functional profiles of two novel mycobacterial antigens Rv2251 and Rv2721c during T cell recall response via multi-color flow cytometry. Healthy household contacts of TB (latent/HHC) and active pulmonary TB (PTB) patients were recruited to investigate the difference in antigen specific T cell recall response. These two antigens induced expansion of CD45RA-CCR7+central memory subtypes and CD45RA-CCR7-effector memory cells in latent population which suggests their possible association with HHC. Rv2251 and Rv2721c antigen specific IFN-γ, TNF-α and IL-2 response was also significantly high in HHC when compared to the PTB (p < 0.005, p < 0.05 and p < 0.05 respectively). The frequency of multifunctional T cells also was high in HHC compared to the PTB with statistical significance only for the antigen Rv2251. Often, the dominant Th1 immune response in HHC is correlated with the protection against the active TB disease. Collectively, we report the first insights into Rv2251 and Rv2721c antigen specific immune response in human donors of TB and provide the immunologic rationale for selecting them for vaccine development against TB.
authors.affiliation: Department of Immunology, National Institute for Research in Tuberculosis (ICMR), (Formerly Tuberculosis Research Centre), No.1, Mayor Sathyamoorthy Road, Chetpet, Chennai 600 031, India.
authors.forename: D
authors.initials: D
authors.lastname: Santhi
authors.affiliation: Department of Immunology, National Institute for Research in Tuberculosis (ICMR), (Formerly Tuberculosis Research Centre), No.1, Mayor Sathyamoorthy Road, Chetpet, Chennai 600 031, India. Electronic address: alamelur@nirt.res.in.
authors.forename: Alamelu
authors.initials: A
authors.lastname: Raja
mesh_terms: D000328:Adult; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D018791:CD4 Lymphocyte Count; D017931:DNA Primers; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D007194:India; D007371:Interferon-gamma; D007376:Interleukin-2; D055985:Latent Tuberculosis / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D013601:T-Lymphocytes; D032581:Tuberculosis Vaccines; D014397:Tuberculosis, Pulmonary / Q000235:genetics / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D017931:DNA Primers; D007376:Interleukin-2; D032581:Tuberculosis Vaccines; D007371:Interferon-gamma
keywords: Latent and active tuberculosis; M. tuberculosis; Multicolur flow cytometry; T cell response; Whole blood culture