<i>In silico</i> designing of a multitope vaccine against <i>Rhizopus</i> microspores

Escherichia fergusonii a gram-negative rod-shaped bacterium in the Enterobacteriaceae family, infect humans, causing serious illnesses such as urinary tract infection, cystitis, biliary tract infection, pneumonia, meningitis, hemolytic uremic syndrome, and death. Initially treatable with penicillin, antibiotic misuse led to evolving resistance, including resistance to colistin, a last-resort drug. With no licensed vaccine, the study aimed to design a multi-epitope vaccine against E. fergusonii. The study started with the retrieval of the complete proteome of all known strains and proceeded to filter the surface exposed virulent proteins. Seventeen virulent proteins (4 extracellular, 4 outer membranes, 9 periplasmic) with desirable physicochemical properties were identified from the complete proteome of known strains. Further, these proteins were processed for B-cell and T-cell epitope mapping. Obtained epitopes were evaluated for antigenicity, allergenicity, solubility, MHC-binding, and toxicity and the filtered epitopes were fused by specific linkers and an adjuvant into a vaccine construct. Structure of the vaccine candidate was predicted and refined resulting in 78.1% amino acids in allowed regions and VERIFY3D score of 81%. Vaccine construct was docked with TLR-4, MHC-I, and MHC-II, showing binding energies of -1040.8 kcal/mol, -871.4 kcal/mol, and -1154.6 kcal/mol and maximum interactions. Further, molecular dynamic simulation of the docked complexes was carried out resulting in a significant stable nature of the docked complexes (high B-factor and deformability values, lower Eigen and high variance values) in terms of intermolecular binding conformation and interactions. The vaccine was also reported to stimulate a variety of immunological pathways after administration. In short, the designed vaccine revealed promising predictions about its immune protective potential against E. fergusonii infections however experimental validation is needed to validate the results.

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Construction of an aerolysin-based multi-epitope vaccine against Aeromonas hydrophila: an in silico machine learning and artificial intelligence-supported approach

Alawam,

Alwethaynani

2024

Front. Immunol.

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Aeromonas hydrophila, a gram-negative coccobacillus bacterium, can cause various infections in humans, including septic arthritis, diarrhea (traveler’s diarrhea), gastroenteritis, skin and wound infections, meningitis, fulminating septicemia, enterocolitis, peritonitis, and endocarditis. It frequently occurs in aquatic environments and readily contacts humans, leading to high infection rates. This bacterium has exhibited resistance to numerous commercial antibiotics, and no vaccine has yet been developed. Aiming to combat the alarmingly high infection rate, this study utilizes in silico techniques to design a multi-epitope vaccine (MEV) candidate against this bacterium based on its aerolysin toxin, which is the most toxic and highly conserved virulence factor among the Aeromonas species. After retrieval, aerolysin was processed for B-cell and T-cell epitope mapping. Once filtered for toxicity, antigenicity, allergenicity, and solubility, the chosen epitopes were combined with an adjuvant and specific linkers to create a vaccine construct. These linkers and the adjuvant enhance the MEV’s ability to elicit robust immune responses. Analyses of the predicted and improved vaccine structure revealed that 75.5%, 19.8%, and 1.3% of its amino acids occupy the most favored, additional allowed, and generously allowed regions, respectively, while its ERRAT score reached nearly 70%. Docking simulations showed the MEV exhibiting the highest interaction and binding energies (−1,023.4 kcal/mol, −923.2 kcal/mol, and −988.3 kcal/mol) with TLR-4, MHC-I, and MHC-II receptors. Further molecular dynamics simulations demonstrated the docked complexes’ remarkable stability and maximum interactions, i.e., uniform RMSD, fluctuated RMSF, and lowest binding net energy. In silico models also predict the vaccine will stimulate a variety of immunological pathways following administration. These analyses suggest the vaccine’s efficacy in inducing robust immune responses against A. hydrophila. With high solubility and no predicted allergic responses or toxicity, it appears safe for administration in both healthy and A. hydrophila-infected individuals.

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In silico designing of a multitope vaccine against Rhizopus microspores

Cited by 3 publications

References 19 publications

Computational exploration and design of a multi-epitopes vaccine construct against Chlamydia psittaci

Computational exploration and design of a multi-epitopes vaccine construct against Chlamydia psittaci

Design of a novel multi-epitopes vaccine against Escherichia fergusonii: a pan-proteome based in- silico approach

Construction of an aerolysin-based multi-epitope vaccine against Aeromonas hydrophila: an in silico machine learning and artificial intelligence-supported approach

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