Immunoinformatic approach employing modeling and simulation to design a novel vaccine construct targeting MDR efflux pumps to confer wide protection against typhoidal<i>Salmonella</i>serovars

Mahapatra, Soumya Ranjan; Dey, Jyotirmayee; Kushwaha, G.S.; Puhan, Puspasree; Mohakud, Nirmal Kumar; Panda, Santosh Kumar; Lata, Surabhi; Misra, Namrata; Suar, Mrutyunjay

doi:10.1080/07391102.2021.1964600

Cited by 34 publications

(15 citation statements)

References 44 publications

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“…There was a rise in the levels of IFN-g, TGF-B, IL-10, and IL-12, which are in line with the report of high levels of cytokines in the recovered individuals from Pseudomonas infection. The decrease in Simpson value ‘D’ over time suggests a complex immune response, which is understandable given the chimera vaccine’s several epitopes [ 33 ]. This immunogenicity profile shows the emergence of immunological memory and, as a result, higher antigen clearance in subsequent exposures.…”

Section: Resultsmentioning

confidence: 99%

Molecular Characterization and Designing of a Novel Multiepitope Vaccine Construct Against Pseudomonas aeruginosa

Dey

Mahapatra

Patnaik

et al. 2022

Int J Pept Res Ther

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Pseudomonas aeruginosa , an ESKAPE pathogen causes many fatal clinical diseases in humans across the globe. Despite an increase in clinical instances of Pseudomonas infection, there is currently no effective vaccine or treatment available. The major membrane protein candidate of the P. aeruginosa bacterial cell is known to be a critical component for cellular bacterial susceptibility to antimicrobial peptides and survival inside the host organisms. Therefore, the current computational study aims to examine P. aeruginosa’s major membrane protein, OprF, and OprI, in order to design linear B-cell, cytotoxic T-cell, and helper T-cell peptide-based vaccine constructs. Utilizing various immune-informatics tools and databases, a total of two B-cells and twelve T-cells peptides were predicted. The final vaccine design was simulated to generate a high-quality three-dimensional structure, which included epitopes, adjuvant, and linkers. The vaccine was shown to be nonallergenic, antigenic, soluble, and had the best biophysical properties. The vaccine and Toll-like receptor 4 have a strong and stable interaction, according to protein-protein docking and molecular dynamics simulations. Additionally, in silico cloning was employed to see how the developed vaccine expressed in the pET28a (+) vector. Ultimately, an immune simulation was performed to see the vaccine efficacy. In conclusion, the newly developed vaccine appears to be a promising option for a vaccine against P. aeruginosa infection. Graphical Abstract Supplementary Information The online version contains supplementary material available at 10.1007/s10989-021-10356-z.

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Section: Resultsmentioning

confidence: 99%

Molecular Characterization and Designing of a Novel Multiepitope Vaccine Construct Against Pseudomonas aeruginosa

Dey

Mahapatra

Patnaik

et al. 2022

Int J Pept Res Ther

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“…Vaccination is a widely employed technique for improving the host immune mechanism against a specific pathogen [ 40 , 41 ]. Producing a range of vaccines, such as live or attenuated vaccines, is expensive, time-consuming, and takes a long time to reach the market [ 42 , 43 ]. Moreover, the attenuated vaccine delivers poor passive immunization and causes allergic responses due to the large antigenic load [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Designing a novel multi-epitope vaccine to evoke a robust immune response against pathogenic multidrug-resistant Enterococcus faecium bacterium

et al. 2022

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Enterococcus faecium is an emerging ESKAPE bacterium that is capable of causing severe public health complications in humans. There are currently no licensed treatments or vaccinations to combat the deadly pathogen. We aimed to design a potent and novel prophylactic chimeric vaccine against E. faecium through an immunoinformatics approach The antigenic Penicillin-binding protein 5 (PBP 5) protein was selected to identify B and T cell epitopes, followed by conservancy analysis, population coverage, physiochemical assessment, secondary and tertiary structural analysis. Using various immunoinformatics methods and tools, two linear B-cell epitopes, five CTL epitopes, and two HTL epitopes were finally selected for vaccine development. The constructed vaccine was determined to be highly immunogenic, cytokine-producing, antigenic, non-toxic, non-allergenic, and stable, as well as potentially effective against E. faecium. In addition, disulfide engineering, codon adaptation, and in silico cloning, were used to improve stability and expression efficiency in the host E. coli. Molecular docking and molecular dynamics simulations indicated that the structure of the vaccine is stable and has a high affinity for the TLR4 receptor. The immune simulation results revealed that both B and T cells had an increased response to the vaccination component. Conclusively, the in-depth in silico analysis suggests, the proposed vaccine to elicit a robust immune response against E. faecium infection and hence a promising target for further experimental trials.

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“…Selecting a suitable linker is crucial for the appropriate binding of protein fragments in a multi-epitope structure. The linkers are responsible for connecting protein segments and have an essential role in maintaining the biological activity and increasing the expression of the structure (Chen et al 2013 ; Li et al 2016 ; Mahapatra et al 2021 ). The EAAAK (Glu–Ala–Ala–Ala–Lys) sequence is a tough and helix-forming linker.…”

Section: Discussionmentioning

confidence: 99%

B-Cell Epitope Mapping from Eight Antigens of Candida albicans to Design a Novel Diagnostic Kit: An Immunoinformatics Approach

Vahedi

Ghasemi

Atapour

et al. 2022

Int J Pept Res Ther

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Invasive candidiasis is an emerging fungal infection and a leading cause of morbidity in health care facilities. Despite advances in antifungal therapy, increased antifungal drug resistance in Candida albicans has enhanced patient fatality. The most common method for Candida albicans diagnosing is blood culture, which has low sensitivity. Therefore, there is an urgent need to establish a valid diagnostic method. Our study aimed to use the bioinformatics approach to design a diagnostic kit for detecting Candida albicans with high sensitivity and specificity. Eight antigenic proteins of Candida albicans (HYR1, HWP1, ECE1, ALS, EAP1, SAP1, BGL2, and MET6) were selected. Next, a construct containing different immunodominant B-cell epitopes was derived from the antigens and connected using a suitable linker. Different properties of the final construct, such as physicochemical properties, were evaluated. Moreover, the designed construct underwent 3D modeling, reverse translation, and codon optimization. The results confirmed that the designed construct could identify Candida albicans with high sensitivity and specificity in serum samples of patients with invasive candidiasis. However, experimental studies are needed for final confirmation. Supplementary Information The online version contains supplementary material available at 10.1007/s10989-022-10413-1.

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Immunoinformatic approach employing modeling and simulation to design a novel vaccine construct targeting MDR efflux pumps to confer wide protection against typhoidalSalmonellaserovars

Cited by 34 publications

References 44 publications

Molecular Characterization and Designing of a Novel Multiepitope Vaccine Construct Against Pseudomonas aeruginosa

Molecular Characterization and Designing of a Novel Multiepitope Vaccine Construct Against Pseudomonas aeruginosa

Designing a novel multi-epitope vaccine to evoke a robust immune response against pathogenic multidrug-resistant Enterococcus faecium bacterium

B-Cell Epitope Mapping from Eight Antigens of Candida albicans to Design a Novel Diagnostic Kit: An Immunoinformatics Approach

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