Designing a Novel Multi-epitope DNA- Based Vaccine Against Tuberculosis: In Silico Approach

Moradi, Jale; Tabrizi, Mina; Izad, Maryam; Mosavari, Nader; Feizabadi, Mohammad Mehdi

doi:10.5812/jjm.43950

Cited by 13 publications

(13 citation statements)

References 52 publications

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“…The problems associated with subunit vaccines are high production costs, inefficient bioavailability, low antigen stability during formulation or hydrolysis, and inactivation process (6). Therefore, computational analysis is the first choice for rational design and is considered as the best economical option to predict and process synthetic subunit vaccine properties (16). Multi-epitope subunit vaccines are new strategies which are developed to produce highly efficient vaccines.…”

Section: Discussionmentioning

confidence: 99%

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In Silico Design of Multi-Epitope ESAT-6:Ag85b:Fcγ2a Fusion Protein as a Novel Candidate for Tuberculosis Vaccine

Karbalaei

Keikha

Ghazvini

2020

Arch Clin Infect Dis

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: Mycobacterium tuberculosis (MTB), which is the causative agent of tuberculosis (TB), is among the most important infectious bacteria with high morbidity and mortality rates worldwide. Bacilli Calmette-Guerin (BCG) vaccine has been discovered for about a century, and it is considered as a major vaccine for humans. However, some factors, such as its attenuated nature and its inefficacy against the latent form of the disease, have led to the use of alternative vaccines. Multi-epitope subunit vaccines are new-generation vaccines that are being developed in clinical trial phases. For the production of a subunit vaccine, the selection of immunodominant antigens and targeted delivery systems to antigen presenting cells (APCs) are considered as basic parameters. In the present study, we designed the novel multi-epitope ESAT-6:Ag85B:Fcγ2a, which was evaluated completely by various online tools as an optimum vaccine against TB. The early secreted antigenic target of 6 kDa (ESAT-6) and antigen 85B (Ag85B) are two immunodominant antigens, and Fcγ2a is a targeted delivery system. This vaccine candidate can be used for future preclinical studies.

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Section: Discussionmentioning

confidence: 99%

“…Modification of the new construct may affect the structure of constructs. Therefore, modified structures were predicted by several online servers, which are listed in Table 1 (15,16).…”

Section: Post-translational Modification (Ptms) Of Multi-epitopes Conmentioning

confidence: 99%

In Silico Design of Multi-Epitope ESAT-6:Ag85b:Fcγ2a Fusion Protein as a Novel Candidate for Tuberculosis Vaccine

Karbalaei

Keikha

Ghazvini

2020

Arch Clin Infect Dis

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“…It is, therefore, essential to screen prevalent HLA alleles in the population of interest and to assess the binding affinities of putative epitopes with these alleles (Braciale et al 1987). These strategies help in designing population-specific vaccines and have been successful for various pathogens (Ashraf et al 2016;Chakraborty et al 2010;Khan et al 2015;Mahmood et al 2019;Moradi et al 2017). In the recent past, a few studies on epitope-based vaccine designing for Mtb have come forward, Mistry and Flower, in 2017, designed an epitope ensemble against TB, however, they did not mention the allergenic natures as well as the population specificity for this epitope ensemble (Mistry and Flower 2017).…”

Section: Discussionmentioning

confidence: 99%

Analysis of Putative Epitope Candidates of Mycobacterium tuberculosis Against Pakistani Human Leukocyte Antigen Background: An Immunoinformatic Study for the Development of Future Vaccine

Mahmood

Bin-T-Abid

Irshad

et al. 2020

Int J Pept Res Ther

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Tuberculosis (TB), a chronic disease caused by Mycobacterium tuberculosis (Mtb), is a global health issue across the world. Pakistan ranks fifth among the countries, which are facing, a significantly great number of mortalities and morbidities due to TB. Unfortunately, all previously reported treatments are not successful for the eradication of TB. Here in this study, we report an emerging treatment option for this disease. We have applied immunoinformatics to predict highly conserved B and T-cell epitopes from Mtb, showing significant binding affinities to the frequent HLA alleles in the Pakistani population. A total of ten highly referenced and experimentally validated epitopes were selected from the Immune Epitope Database (IEDB), followed by their conservancy analysis using weblogos. The consensus sequences and variants derived from these sequences were examined, for their binding affinities, with prevalent HLA alleles of Pakistan. Moreover, the antigenic and allergenic natures of these peptides were also evaluated via Vaxijen and AllerTOP, respectively. Consequently, all potentially allergenic and non-antigenic, peptide fragments, were excluded from the analysis. Among all putative epitopes, three CD8 + T-cell epitopes were selected, as ideal vaccine candidates and, population coverage analysis revealed that the combination of these three peptides was covering, 67.28% Pakistani Asian and 57.15% mixed Pakistani populations. Likewise, eleven linear and six conformational or discontinuous B-cell epitopes were also marked as potential vaccine candidates based on their prediction score, non-allergenic nature, and antigenic properties. These epitopes, however, need the final validation via wet-lab studies. After their approval, these epitopes would be effective candidates for the future designing of epitope-based vaccines against Mtb infections in Pakistan.

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“…MHC class I and II epitopes were fused together tandemly with appropriate linkers to avoid interferences in epitope processing ( Figure 1A). In another design, LC3 was directly fused to the C-terminus of the multi-epitope peptide [22]. In this study, the latest peptides were utilized for reverse translation and codon optimization.…”

Section: Design and Construction Of Dna Plasmidsmentioning

confidence: 99%

“…In the previous study, a multi-epitope DNA with or without LC3 was designed and analyzed [22]. In this study, codon-optimized genes were synthetized and DNA constructs were created and the immunogenicity of DNA constructs was evaluated in BALB/c mice.…”

Section: Introductionmentioning

confidence: 99%

Specific immune responses induced by multi-epitope DNA derived from Mycobacterium tuberculosis DosR antigens

Moradi

Izad

Tabrizi

et al. 2018

AMicr

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One third of the world population are latently infected with Mycobacterium tuberculosis and are at the risk of reactivation of tuberculosis (TB). The most effective strategy for control of TB worldwide is the development of a vaccine that inhibits progression of latent TB to active infection. In this study, two optimized constructs consisting of multi-epitopes DNA derived from three latency antigens Rv2029c, Rv2031c, and Rv2627c fused with or without light chain 3 (LC3) are synthetized. The immunogenicity effectiveness of two DNA constructs was evaluated in the mouse model. LC3-fused multi-epitope DNA construct induced strong specific Th1 immune responses with high increase in IFN-γ CD4 and IL-2 CD4 T cell populations (both with p < 0.0001) and IFN-γ IL-2 CD4 T cell population (p < 0.0001) compared with empty vector, BCG, and multi-epitope DNA construct groups. The LC3-fused construct induced IFN-γ CD8 T cell population (p < 0.0001) compared with empty vector and BCG groups but could not induce the T cell population compared with construct without LC3. Importantly, LC3-fused DNA construct did not induce epitope-specific IL-4 and IL-10 from CD4 and CD8 T cell populations. The results indicated that LC3-fused multi-epitope DNA construct has a potential to be investigated for future development of a new TB vaccine.

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Designing a Novel Multi-epitope DNA- Based Vaccine Against Tuberculosis: In Silico Approach

Cited by 13 publications

References 52 publications

In Silico Design of Multi-Epitope ESAT-6:Ag85b:Fcγ2a Fusion Protein as a Novel Candidate for Tuberculosis Vaccine

In Silico Design of Multi-Epitope ESAT-6:Ag85b:Fcγ2a Fusion Protein as a Novel Candidate for Tuberculosis Vaccine

Analysis of Putative Epitope Candidates of Mycobacterium tuberculosis Against Pakistani Human Leukocyte Antigen Background: An Immunoinformatic Study for the Development of Future Vaccine

Specific immune responses induced by multi-epitope DNA derived from Mycobacterium tuberculosis DosR antigens

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