In silico identification of potential antigenic proteins and promiscuous CTL epitopes in Mycobacterium tuberculosis

Sundaramurthi, Jagadish Chandrabose; Brindha, S.; Shobitha, S.R.; Swathi, A.; Ramanandan, P.; Hanna, Luke Elizabeth

doi:10.1016/j.meegid.2012.03.023

Cited by 15 publications

(9 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…With the advent of rapid genome sequencing , in silico antigen screens have been used to predict MTB antigens for new vaccines and diagnostics (Cole, ; Chaitra et al ., ; Ewer et al ., ; Zvi et al ., ; Wang et al ., ; Tang et al ., ; Sundaramurthi et al ., ). Many of these screens have focused on the prediction of CD4 and CD8 T‐cell epitopes in an effort to discover antigens capable of stimulating a robust cell‐mediated immune response (Wang et al ., ; Tang et al ., ; Sundaramurthi et al ., ). Inevitably, these studies either incorporate existing published data demonstrating the expression of the protein either in vitro or in vivo or require additional testing to verify actual protein expression.…”

Section: Introductionmentioning

confidence: 99%

Mycobacterium tuberculosispellicles express unique proteins recognized by the host humoral response

et al. 2014

View full text Add to dashboard Cite

Mycobacterium tuberculosis (MTB) causes both acute and chronic infections in humans characterized by tolerance to antibiotics and reactivation to cause secondary tuberculosis. These characteristics have led to renewed interested in the in vitro pellicle, or biofilm mode of growth, where bacteria grow to produce a thick aggregate at the air-liquid interface and exhibit increased phenotypic resistance to antibiotics. We infected guinea pigs with the virulent H37Rv strain of MTB for 60 days at which point we collected blood. To identify antigenic proteins, membrane protein extracts of MTB H37Ra pellicles and shaken cultures grown for 3, 5, or 7 weeks were probed with the infected animals’ sera after the proteins were separated by two-dimensional gel electrophoresis (2DGE). Antigenic proteins were then identified using MALDI-TOF/TOF mass spectrometry peptide mass fingerprinting. Antigenic pellicle proteins were compared across the three timepoints to identify those that were produced consistently during pellicle growth. They were also compared to those membrane proteins identified from harvested shaken cultures to determine pellicle-specific versus universally-expressed proteins. Using this technique we identified 44 distinct antigenic proteins, nine of which were pellicle-specific. The sequence of antigenic pellicle-specific proteins was checked for sequence conservation across 15 sequenced MTB clinical isolates, three other members of the MTB complex, as well as Mycobacterium avium and Mycobacterium smegmatis. The antigenic pellicle-specific protein Rv0097 was found to have very high sequence conservation within the MTB complex but not with related mycobacteria while FabG4 was highly conserved in all mycobacteria analyzed. These conserved pellicle-specific proteins represent targets for the development of future diagnostic tests and vaccines.

show abstract

Section: Introductionmentioning

confidence: 99%

Mycobacterium tuberculosispellicles express unique proteins recognized by the host humoral response

et al. 2014

View full text Add to dashboard Cite

show abstract

“…The immunity sought is a protective response that is cellular. Therefore, immunoinformatics is based on the study of T-cell epitopes [22,[48][49][50].…”

Section: Tuberculosismentioning

confidence: 99%

The Impact of Bioinformatics on Vaccine Design and Development

María¹,

Arturo²,

Alicia³

et al. 2017

Vaccines

View full text Add to dashboard Cite

Vaccines are the pharmaceutical products that ofer the best cost-beneit ratio in the prevention or treatment of diseases. In that a vaccine is a pharmaceutical product, vaccine development and production are costly and it takes years for this to be accomplished. Several approaches have been applied to reduce the times and costs of vaccine development, mainly focusing on the selection of appropriate antigens or antigenic structures, carriers, and adjuvants. One of these approaches is the incorporation of bioinformatics methods and analyses into vaccine development. This chapter provides an overview of the application of bioinformatics strategies in vaccine design and development, supplying some successful examples of vaccines in which bioinformatics has furnished a cuting edge in their development. Reverse vaccinology, immunoinformatics, and structural vaccinology are described and addressed in the design and development of speciic vaccines against infectious diseases caused by bacteria, viruses, and parasites. These include some emerging or re-emerging infectious diseases, as well as therapeutic vaccines to ight cancer, allergies, and substance abuse, which have been facilitated and improved by using bioinformatics tools or which are under development based on bioinformatics strategies.

show abstract

“…The “in silico” algorithms (ProPred1) predicted a number of HLA class I-permissive epitopes in histone or proteins of undefined function from Mtb (37). ProPred prediction of Mycobacterium leprae epitopes identified a number of both class I and II, HLA-permissive T-cell reactivity, in leprosy endemic populations in Brazil, Ethiopia, and Nepal (38).…”

Section: Mhc-permissive Epitopesmentioning

confidence: 99%

Function and Potentials of M. tuberculosis Epitopes

Iványi

2014

Front. Immunol.

View full text Add to dashboard Cite

Study of the function of epitopes of Mycobacterium tuberculosis antigens contributed significantly toward better understanding of the immunopathogenesis and to efforts for improving infection and disease control. Characterization of genetically permissively presented immunodominant epitopes has implications for the evolution of the host–parasite relationship, development of immunodiagnostic tests, and subunit prophylactic vaccines. Knowledge of the determinants of cross-sensitization, relevant to other pathogenic or environmental mycobacteria and to host constituents has advanced. Epitope-defined IFNγ assay kits became established for the specific detection of infection with tubercle bacilli both in humans and cattle. The CD4 T-cell epitope repertoire was found to be more narrow in patients with active disease than in latently infected subjects. However, differential diagnosis of active TB could not be made reliably merely on the basis of epitope recognition. The mechanisms by which HLA polymorphism can influence the development of multibacillary tuberculosis (TB) need further analysis of epitopes, recognized by Th2 helper cells for B-cell responses. Future vaccine development would benefit from better definition of protective epitopes and from improved construction and formulation of subunits with enhanced immunogenicity. Epitope-defined serology, due to its operational advantages is suitable for active case finding in selected high disease incidence populations, aiming for an early detection of infectious cases and hence for reducing the transmission of infection. The existing knowledge of HLA class I binding epitopes could be the basis for the construction of T-cell receptor-like ligands for immunotherapeutic application. Continued analysis of the functions of mycobacterial epitopes, recognized by T cells and antibodies, remains a fertile avenue in TB research.

show abstract

In silico identification of potential antigenic proteins and promiscuous CTL epitopes in Mycobacterium tuberculosis

Cited by 15 publications

References 46 publications

Mycobacterium tuberculosispellicles express unique proteins recognized by the host humoral response

Mycobacterium tuberculosispellicles express unique proteins recognized by the host humoral response

The Impact of Bioinformatics on Vaccine Design and Development

Function and Potentials of M. tuberculosis Epitopes

Contact Info

Product

Resources

About