In silicoanalysis of potential human T Cell antigens fromMycobacterium tuberculosisfor the development of subunit vaccines against tuberculosis

Abstract

In silico analysis was used to predict MHC class I and class II promiscuous epitopes and potential antigens, from 24 novel T cell antigens of Mycobacterium tuberculosis. Majority of the antigens (16/24) had high affinity peptides to both MHC class I and class II alleles and higher population coverage compared to well-proven T cell antigens ESAT-6, CFP-10 and Ag85B. Among these, highest population coverage were calculated for three novel T cell antigens Rv0733 (97.24%), Rv0462 (96.9%) and Rv2251 (96.3%). The prediction results were experimentally tested by in vitro stimulation of these novel T cell antigens with blood drawn from QuantiFERON-TB Gold In-Tube (QFT-IT) positive healthy household contacts of tuberculosis patients and pulmonary TB patients. Significantly higher level interferon-γ (IFN-γ) was observed, with these novel T cell antigens, in healthy household contacts compared to pulmonary TB subjects (p = 0.0001). In silico analysis also resulted in prediction of 36 promiscuous epitopes from the novel 24 T cell antigens. Population coverage for 4 out of the 36 promiscuous epitopes was >90% [67 VVLLWSPRS (Rv1324), 42 VVGVTTNPS (Rv1448c), 178 MRFLLSAKS (Rv0242c) and 842 IRLMALVEY (Rv3800c)]. Our results shows that these novel antigens and promiscuous epitopes identified from our analysis can further be investigated for their usefulness for subunit vaccine development.

Dihydrolipoamide dehydrogenase-Lpd (Rv0462)-specific T cell recall responses are higher in healthy household contacts of TB: a novel immunodominant antigen from M. tuberculosis

“…ESAT-6 and CFP-10 were received as recombinant plasmids from Colorado State University (Fort Collins, Colorado, USA), and the test antigen Lpd (Rv0462) was obtained by in vitro cloning and overexpression [14]. ESAT-6 and CFP-10 were received as recombinant plasmids from Colorado State University (Fort Collins, Colorado, USA), and the test antigen Lpd (Rv0462) was obtained by in vitro cloning and overexpression [14].…”

“…The potential of Lpd to induce dendritic cells, a key component in bridging innate and adaptive immune responses toward Th1 polarization, is already proven [13]. However, Lpd-specific T cell profiles were not explicitly analyzed [14]. In silico analysis of T cell antigens from culture filtrate antigens of M. tuberculosis resulted in a higher percentage of class I and class II MHC alleles and higher population coverage by Lpd compared with standard mycobacterial antigens ESAT-6, CFP-10, and Ag85B.…”

Identification of putative unique immunogenic ZIKV and DENV1-4 peptides for diagnostic cellular based tests

“…Prior work with H1N1 [ref. 12], Hepatitis B 13 , and Mycobacterial infections 14, 15 has demonstrated the utility of epitope recognition in the development of novel diagnostics and vaccines. Therefore, we propose that detection of a specific lingering cytotoxic T-lymphocyte (CTL) memory response against Zika and/or Dengue, unlike antibody responses, would allow these infections to be distinguished.…”

Multiantigenic subunitary vaccines against tuberculosis in clinical trials: Where do we stand and where do we need to go?

“…18 Other mycobacterial antigens, relevant at different stages of infection, have also been evaluated, such as the combination of Mtb32 (a secreted serine protease) plus Mtb39, termed M72, which in combination with adjuvant AS01 E has shown an acceptable safety profile and induced a potent M72-specific CD4C T cell response in clinical trials performed in adults, even Mtb-infected people, [19][20][21][22] and recently shown to induce robust T cell and antibody responses in HIV-negative adolescents living a TBendemic setting. 23 More recently, approaches to propose new vaccine candidates have been refined by finding T-cell epitopes recognized by individuals suffering from active or latent disease, with bioinformatics being fundamental in predicting new potential targets for the immune system, 24 either from the dominant class of antigens or those that are not as strong as the so called dominant but that still play a relevant role during some part of the interaction with the host critical for establishment of persistence of infection. OMICs technologies (genomics, transcriptomics, proteomics and metabolomics) also start to play a highly prominent role, by making possible to unravel very discrete yet quintessential molecules for M. tuberculosis life cycle that would result in rationally designed vaccine candidates.…”