Prediction and evaluation of multi epitope based sub-unit vaccine against Salmonella typhimurium

Zafar, Samavia; Ajab, Huma; Mughal, Zaib-un-nisa; Zai, Jawaid Ahmed; Baig, Sofia; Baig, Ayesha; Habib, Zeshan; Jamil, Farrukh; Ibrahim, Muhammad; Kanwal, Sumaira; Rasheed, Muhammad

doi:10.1016/j.sjbs.2021.09.061

Cited by 18 publications

(7 citation statements)

References 49 publications

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“…Several previous studies have employed similar approaches to design multi-epitope vaccine, however, unlike our present studies, they targeted a particular strain of Salmonella [91]- [94]. Here, to develop a pan-Salmonella vaccine, we targeted the core proteome of Salmonella to design a vaccine that will be effective against a broad spectrum of Salmonella infections.…”

Section: Discussionmentioning

confidence: 99%

“…Multi-epitope-based vaccines were preferred over conventional vaccines due to their cost-effectiveness, superior safety, and the ability to tailor epitopes intelligently for increased potency [89], [90]. Several previous studies have employed similar approaches to design multi-epitope vaccine, however, unlike our present studies, they targeted a particular strain of Salmonella [91]–[94]. Here, to develop a pan- Salmonella vaccine, we targeted the core proteome of Salmonella to design a vaccine that will be effective against a broad spectrum of Salmonella infections.…”

Section: Discussionmentioning

confidence: 99%

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An Integrated Comparative Genomics, Subtractive Proteomics and Immunoinformatics Framework for the Rational Design of a Pan-SalmonellaMulti-Epitope Vaccine

Bhattacharjee,

Hosen,

Lamisa

et al. 2023

Preprint

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Salmonella infections are a global public health issue due to the high cost of illness surveillance, prevention, and treatment. In this study, we explored the core proteome in Salmonella to design a multi-epitope vaccine through Subtractive Proteomics and immunoinformatics approaches. A total of 2395 core proteins presents in 30 different strains of Salmonella (reference strain-NZ CP014051) were curated. Utilizing the subtractive proteomics approach on the Salmonella core proteome, Curlin major subunit A (CsgA) was selected as the vaccine candidate. csgA is a conserved gene that is related with biofilm formation. Immunodominant B and T cell epitopes from CsgA were predicted using numerous immunoinformatics tools. T lymphocyte epitopes had adequate population coverage and their corresponding MHC alleles showed significant binding scores after peptide-protein based molecular docking. Afterward, a multiepitope vaccine was constructed with peptide linkers and Human Beta Defensin-2 (as an adjuvant). The vaccine was found to be highly antigenic, non-toxic, non-allergic, and had physicochemical properties. Additionally, Molecular Dynamics Simulation and Immune Simulation demonstrated that the vaccine can bind with Toll Like Receptor 4 and elicit robust immune response. Using in vitro, in vivo, and clinical trials, our results would yield a Pan-Salmonella vaccine that will provide protection against various Salmonella species.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

An Integrated Comparative Genomics, Subtractive Proteomics and Immunoinformatics Framework for the Rational Design of a Pan-SalmonellaMulti-Epitope Vaccine

Bhattacharjee,

Hosen,

Lamisa

et al. 2023

Preprint

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“…Establishing an effective immunological response relies significantly on the interaction between a vaccine protein and host immune cells ( 60 ). To assess how well your MEV could bind to human immunological receptors, molecular docking research was conducted ( 61 ). One specific immunological receptor investigated in this research is Toll-like receptor 4 (TLR4) ( 62 ).…”

Section: Methodsmentioning

confidence: 99%

Designing of a multi-epitopes based vaccine against Haemophilius parainfluenzae and its validation through integrated computational approaches

Ghaffar,

Tahir,

Muhammad

et al. 2024

Front. Immunol.

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Haemophilus parainfluenzae is a Gram-negative opportunist pathogen within the mucus of the nose and mouth without significant symptoms and has an ability to cause various infections ranging from ear, eye, and sinus to pneumonia. A concerning development is the increasing resistance of H. parainfluenzae to beta-lactam antibiotics, with the potential to cause dental infections or abscesses. The principal objective of this investigation is to utilize bioinformatics and immuno-informatic methodologies in the development of a candidate multi-epitope Vaccine. The investigation focuses on identifying potential epitopes for both B cells (B lymphocytes) and T cells (helper T lymphocytes and cytotoxic T lymphocytes) based on high non-toxic and non-allergenic characteristics. The selection process involves identifying human leukocyte antigen alleles demonstrating strong associations with recognized antigenic and overlapping epitopes. Notably, the chosen alleles aim to provide coverage for 90% of the global population. Multi-epitope constructs were designed by using suitable linker sequences. To enhance the immunological potential, an adjuvant sequence was incorporated using the EAAAK linker. The final vaccine construct, comprising 344 amino acids, was achieved after the addition of adjuvants and linkers. This multi-epitope Vaccine demonstrates notable antigenicity and possesses favorable physiochemical characteristics. The three-dimensional conformation underwent modeling and refinement, validated through in-silico methods. Additionally, a protein-protein molecular docking analysis was conducted to predict effective binding poses between the multi-epitope Vaccine and the Toll-like receptor 4 protein. The Molecular Dynamics (MD) investigation of the docked TLR4-vaccine complex demonstrated consistent stability over the simulation period, primarily attributed to electrostatic energy. The docked complex displayed minimal deformation and enhanced rigidity in the motion of residues during the dynamic simulation. Furthermore, codon translational optimization and computational cloning was performed to ensure the reliability and proper expression of the multi-Epitope Vaccine. It is crucial to emphasize that despite these computational validations, experimental research in the laboratory is imperative to demonstrate the immunogenicity and protective efficacy of the developed vaccine. This would involve practical assessments to ascertain the real-world effectiveness of the multi-epitope Vaccine.

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“…Typhimurium outbreaks have become increasingly prevalent, with a significant proportion associated with multidrug-resistant strains [ 6–9 ]. Despite ongoing endeavours to develop novel treatment strategies, antibiotics such as fluoroquinolones, aminoglycosides, and β-lactams remain pivotal in Salmonella Typhimurium therapy [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Tobramycin-resistant small colony variant mutant of Salmonella enterica serovar Typhimurium shows collateral sensitivity to nitrofurantoin

Wang,

Zhang,

Chu

et al. 2024

Virulence

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The increasing antibiotic resistance poses a significant global health challenge, threatening our ability to combat infectious diseases. The phenomenon of collateral sensitivity, whereby resistance to one antibiotic is accompanied by increased sensitivity to another, offers potential avenues for novel therapeutic interventions against infections unresponsive to classical treatments. In this study, we elucidate the emergence of tobramycin (TOB)-resistant small colony variants (SCVs) due to mutations in the hemL gene, which render S . Typhimurium more susceptible to nitrofurantoin (NIT). Mechanistic studies demonstrate that the collateral sensitivity in TOB-resistant S . Typhimurium SCVs primarily stems from disruptions in haem biosynthesis. This leads to dysfunction in the electron transport chain (ETC) and redox imbalance, ultimately inducing lethal accumulation of reactive oxygen species (ROS). Additionally, the upregulation of nfsA/B expressions facilitates the conversion of NIT prodrug into its active form, promoting ROS-mediated bacterial killing and contributing to this collateral sensitivity pattern. Importantly, alternative NIT therapy demonstrates a significant reduction of bacterial load by more than 2.24-log 10 cfu/g in the murine thigh infection and colitis models. Our findings corroborate the collateral sensitivity of S . Typhimurium to nitrofurans as a consequence of evolving resistance to aminoglycosides. This provides a promising approach for treating infections due to aminoglycoside-resistant strains.

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Prediction and evaluation of multi epitope based sub-unit vaccine against Salmonella typhimurium

Cited by 18 publications

References 49 publications

An Integrated Comparative Genomics, Subtractive Proteomics and Immunoinformatics Framework for the Rational Design of a Pan-SalmonellaMulti-Epitope Vaccine

An Integrated Comparative Genomics, Subtractive Proteomics and Immunoinformatics Framework for the Rational Design of a Pan-SalmonellaMulti-Epitope Vaccine

Designing of a multi-epitopes based vaccine against Haemophilius parainfluenzae and its validation through integrated computational approaches

Tobramycin-resistant small colony variant mutant of Salmonella enterica serovar Typhimurium shows collateral sensitivity to nitrofurantoin

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