The role of immunoinformatics in the development of T-cell peptide-based vaccines against<i>Mycobacterium tuberculosis</i>

Ortega-Tirado, David; Arvizu‐Flores, Aldo A.; Velázquez, Carlos; Garibay‐Escobar, Adriana

doi:10.1080/14760584.2020.1825950

Cited by 11 publications

(5 citation statements)

References 85 publications

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“…They allow the identification of proteins and antigenic epitopes in B cells to find those responsible for stimulating both humoral and cell-mediated immunity [ 42 , 43 ]. The most efficient way to control diseases such as TB and many intracellular infections is through the identification of T-cell peptides that interact with the peptide-HLA complex and that can cause a cellular immune response [ 46 , 47 ]. In a previous study, the PE_PGRS49 and PE_PGRS56 proteins were identified as highly antigenic in the MTB proteome; consequently, their epitopes were identified and analyzed [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

Design of a Multi-Epitope Vaccine against Tuberculosis from Mycobacterium tuberculosis PE_PGRS49 and PE_PGRS56 Proteins by Reverse Vaccinology

Ruaro-Moreno,

Monterrubio-López,

Reyes-Gastellou

et al. 2023

Microorganisms

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Tuberculosis is a disease caused by Mycobacterium tuberculosis, representing the second leading cause of death by an infectious agent worldwide. The available vaccine against this disease has insufficient coverage and variable efficacy, accounting for a high number of cases worldwide. In fact, an estimated third of the world’s population has a latent infection. Therefore, developing new vaccines is crucial to preventing it. In this study, the highly antigenic PE_PGRS49 and PE_PGRS56 proteins were analyzed. These proteins were used for predicting T- and B-cell epitopes and for human leukocyte antigen (HLA) protein binding efficiency. Epitopes GGAGGNGSLSS, FAGAGGQGGLGG, GIGGGTQSATGLG (PE_PGRS49), and GTGWNGGKGDTG (PE_PGRS56) were selected based on their best physicochemical, antigenic, non-allergenic, and non-toxic properties and coupled to HLA I and HLA II structures for in silico assays. A construct with an adjuvant (RS09) plus each epitope joined by GPGPG linkers was designed, and the stability of the HLA-coupled construct was further evaluated by molecular dynamics simulations. Although experimental and in vivo studies are still necessary to ensure its protective effect against the disease, this study shows that the vaccine construct is dynamically stable and potentially effective against tuberculosis.

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Section: Discussionmentioning

confidence: 99%

Design of a Multi-Epitope Vaccine against Tuberculosis from Mycobacterium tuberculosis PE_PGRS49 and PE_PGRS56 Proteins by Reverse Vaccinology

Ruaro-Moreno,

Monterrubio-López,

Reyes-Gastellou

et al. 2023

Microorganisms

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“…These findings encourage the identification of overlapping reactive epitopes to construct new chimeric vaccine antigens [49,50] as well as other applications related to diagnostics, design of individualized vaccines or as therapeutic targets [51]. The epitope structure is important for chimeric antigen vaccine development and confers the ability to direct the immune response to more effectively target epitopes [34,52].…”

Section: Discussionmentioning

confidence: 99%

“…A limitation of the methodology applied in this study is its restriction to linear epitopes; thus, even if a significant part of an epitope is a short linear peptide, this does not ensure that the peptide represents the entire epitope or that it does not require a different conformation [55]. Even short linear peptides may depend on their three-dimensional conformation for bioactivity [50]. Furthermore, the identification of protective B-cell epitopes may uncover or localize pathogenic functions, especially if the antibodies block targeted B-cell epitopes involved in host-pathogen interaction [56] or interaction with other proteins of the interactome network (protein-protein physical and functional interactions) [44,57], which makes this tool very useful in the control of ticks and tick-borne pathogens.…”

Section: Discussionmentioning

confidence: 99%

The Correlation between Subolesin-Reactive Epitopes and Vaccine Efficacy

Contreras

Kasaija

Kabi³

et al. 2022

Vaccines

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Vaccination is an environmentally-friendly alternative for tick control. The tick antigen Subolesin (SUB) has shown protection in vaccines for the control of multiple tick species in cattle. Additionally, recent approaches in quantum vaccinomics have predicted SUB-protective epitopes and the peptide sequences involved in protein–protein interactions in this tick antigen. Therefore, the identification of B-cell–reactive epitopes by epitope mapping using a SUB peptide array could be essential as a novel strategy for vaccine development. Subolesin can be used as a model to evaluate the effectiveness of these approaches for the identification of protective epitopes related to vaccine protection and efficacy. In this study, the mapping of B-cell linear epitopes of SUB from three different tick species common in Uganda (Rhipicephalus appendiculatus, R. decoloratus, and Amblyomma variegatum) was conducted using serum samples from two cattle breeds immunized with SUB-based vaccines. The results showed that in cattle immunized with SUB from R. appendiculatus (SUBra) all the reactive peptides (Z-score > 2) recognized by IgG were also significant (Z-ratio > 1.96) when compared to the control group. Additionally, some of the reactive peptides recognized by IgG from the control group were also recognized in SUB cocktail–immunized groups. As a significant result, cattle groups that showed the highest vaccine efficacy were Bos indicus immunized with a SUB cocktail (92%), and crossbred cattle were immunized with SUBra (90%) against R. appendiculatus ticks; the IgG from these groups recognized overlapping epitopes from the peptide SPTGLSPGLSPVRDQPLFTFRQVGLICERMMKERESQIRDEYDHVLSAKLAEQYDTFVKFTYDQKRFEGATPSYLS (Z-ratio > 1.96), which partially corresponded to a Q38 peptide and the SUB protein interaction domain. These identified epitopes could be related to the protection and efficacy of the SUB-based vaccines, and new chimeras containing these protective epitopes could be designed using this new approach.

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“…As the derivative of big data and artificial intelligence (AI) technology, bioinformatics tools can also be utilized to screen effective antigen epitopes for fabricating potential vaccine candidates for tuberculosis ( 145 ). Owing to the important function of DNA binding proteins in the process of DNA replication, transcription, regulation and repair, Sunita et al applied DNABIND tool to identify 1453 DNA binding proteins from the genes of Mtb for screening potential tuberculosis vaccines.…”

Section: Subunit Vaccinesmentioning

confidence: 99%

Advance in strategies to build efficient vaccines against tuberculosis

Guo²,

Xu³

et al. 2022

Front. Vet. Sci.

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Tuberculosis is a chronic consumptive infectious disease, which can cause great damage to human and animal health all over the world. The emergence of multi-drug resistant strains, the unstable protective effect of Bacillus Calmette-Guérin (BCG) vaccine on adults, and the mixed infection with HIV all warn people to exploit new approaches for conquering tuberculosis. At present, there has been significant progress in developing tuberculosis vaccines, such as improved BCG vaccine, subunit vaccine, DNA vaccine, live attenuated vaccine and inactivated vaccine. Among these candidate vaccines, there are some promising vaccines to improve or replace BCG vaccine effect. Meanwhile, the application of adjuvants, prime-boost strategy, immunoinformatic tools and targeting components have been studied concentratedly, and verified as valid means of raising the efficiency of tuberculosis vaccines as well. In this paper, the latest advance in tuberculosis vaccines in recent years is reviewed to provide reliable information for future tuberculosis prevention and treatment.

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The role of immunoinformatics in the development of T-cell peptide-based vaccines againstMycobacterium tuberculosis

Cited by 11 publications

References 85 publications

Design of a Multi-Epitope Vaccine against Tuberculosis from Mycobacterium tuberculosis PE_PGRS49 and PE_PGRS56 Proteins by Reverse Vaccinology

Design of a Multi-Epitope Vaccine against Tuberculosis from Mycobacterium tuberculosis PE_PGRS49 and PE_PGRS56 Proteins by Reverse Vaccinology

The Correlation between Subolesin-Reactive Epitopes and Vaccine Efficacy

Advance in strategies to build efficient vaccines against tuberculosis

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