Immunoinformatics Analysis and In-silico Design of Multi- Epitopes Vaccine Against Lassa Virus

Omoniyi, Akinyemi Ademola; Adebisi, Samuel Sunday; Musa, Sunday Abraham; Nzalak, James Oliver; Danborno, Barnabas; Bauchi, Zainab Maryam; Badmus, Iswat Taiwo; Olatomide, Oluwasegun Davis; Oladimeji, Olalekan Jerry; Nyengaard, Jens Randel

doi:10.21203/rs.3.rs-355782/v1

Cited by 3 publications

(3 citation statements)

References 112 publications

(146 reference statements)

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“…This server was used for antigen characterization and its profiling to calculate immune responses of a host, i.e., human. The server was used to run the process of simulation for three separate mammalian organs, i.e., lymph nodes, thymus, and bone marrow, while the parameters used for the process of the simulation were by default [76].…”

Section: C-immune Simulationmentioning

confidence: 99%

Designing a Recombinant Vaccine against Providencia rettgeri Using Immunoinformatics Approach

et al. 2022

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Antibiotic resistance (AR) is the resistance mechanism pattern in bacteria that evolves over some time, thus protecting the bacteria against antibiotics. AR is due to bacterial evolution to make itself fit to changing environmental conditions in a quest for survival of the fittest. AR has emerged due to the misuse and overuse of antimicrobial drugs, and few antibiotics are now left to deal with these superbug infections. To combat AR, vaccination is an effective method, used either therapeutically or prophylactically. In the current study, an in silico approach was applied for the design of multi-epitope-based vaccines against Providencia rettgeri, a major cause of traveler’s diarrhea. A total of six proteins: fimbrial protein, flagellar hook protein (FlgE), flagellar basal body L-ring protein (FlgH), flagellar hook-basal body complex protein (FliE), flagellar basal body P-ring formation protein (FlgA), and Gram-negative pili assembly chaperone domain proteins, were considered as vaccine targets and were utilized for B- and T-cell epitope prediction. The predicted epitopes were assessed for allergenicity, antigenicity, virulence, toxicity, and solubility. Moreover, filtered epitopes were utilized in multi-epitope vaccine construction. The predicted epitopes were joined with each other through specific GPGPG linkers and were joined with cholera toxin B subunit adjuvant via another EAAAK linker in order to enhance the efficacy of the designed vaccine. Docking studies of the designed vaccine construct were performed with MHC-I (PDB ID: 1I1Y), MHC-II (1KG0), and TLR-4 (4G8A). Findings of the docking study were validated through molecular dynamic simulations, which confirmed that the designed vaccine showed strong interactions with the immune receptors, and that the epitopes were exposed to the host immune system for proper recognition and processing. Additionally, binding free energies were estimated, which highlighted both electrostatic energy and van der Waals forces to make the complexes stable. Briefly, findings of the current study are promising and may help experimental vaccinologists to formulate a novel multi-epitope vaccine against P. rettgeri.

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Section: C-immune Simulationmentioning

confidence: 99%

Designing a Recombinant Vaccine against Providencia rettgeri Using Immunoinformatics Approach

et al. 2022

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“…In multi-epitope designing and processing, a multi-epitope vaccine was constructed and then processed [37,38]. In the construction phase, the filtered epitopes were linked through "GPGPG" linkers and linked with "cholera toxin B-subunit adjuvant (CTBS)" via an EAAK linker [20,39,40].…”

Section: Multi-epitope-based Vaccine Designing and Processing Phasementioning

confidence: 99%

Computer-Aided Multi-Epitope Vaccine Design against Enterobacter xiangfangensis

Alshammari

Alharbi

Al-Ghamdi

et al. 2022

IJERPH

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Antibiotic resistance is a global public health threat and is associated with high mortality due to antibiotics’ inability to treat bacterial infections. Enterobacter xiangfangensis is an emerging antibiotic-resistant bacterial pathogen from the Enterobacter genus and has the ability to acquire resistance to multiple antibiotic classes. Currently, there is no effective vaccine against Enterobacter species. In this study, a chimeric vaccine is designed comprising different epitopes screened from E. xiangfangensis proteomes using immunoinformatic and bioinformatic approaches. In the first phase, six fully sequenced proteomes were investigated by bacterial pan-genome analysis, which revealed that the pathogen consists of 21,996 core proteins, 3785 non-redundant proteins and 18,211 redundant proteins. The non-redundant proteins were considered for the vaccine target prioritization phase where different vaccine filters were applied. By doing so, two proteins; ferrichrome porin (FhuA) and peptidoglycan-associated lipoprotein (Pal) were shortlisted for epitope prediction. Based on properties of antigenicity, allergenicity, water solubility and DRB*0101 binding ability, three epitopes (GPAPTIAAKR, ATKTDTPIEK and RNNGTTAEI) were used in multi-epitope vaccine designing. The designed vaccine construct was analyzed in a docking study with immune cell receptors, which predicted the vaccine’s proper binding with said receptors. Molecular dynamics analysis revealed that the vaccine demonstrated stable binding dynamics, and binding free energy calculations further validated the docking results. In conclusion, these in silico results may help experimentalists in developing a vaccine against E. xiangfangensis in specific and Enterobacter in general.

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“…In addition, drug-resistant strains of B. melitensis are making the situation worse. Thus, considering this, herein we applied an integrated approach comprising comparative genomics, subtractive proteomics, reverse vaccinology, immunoinformatic, and biophysics techniques to identify protective antigens from B. melitensis completely sequenced genomes and designed a multi-epitopes vaccine [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ]. The designed vaccine construct then was examined for interactions with host immune receptors to check whether the vaccine is able to be presented to the host immunity system.…”

Section: Introductionmentioning

confidence: 99%

Proteome-Wide Screening of Potential Vaccine Targets against Brucella melitensis

et al. 2023

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The ongoing antibiotic-resistance crisis is becoming a global problem affecting public health. Urgent efforts are required to design novel therapeutics against pathogenic bacterial species. Brucella melitensis is an etiological agent of brucellosis, which mostly affects sheep and goats but several cases have also been reported in cattle, water buffalo, yaks and dogs. Infected animals also represent the major source of infection for humans. Development of safer and effective vaccines for brucellosis remains a priority to support disease control and eradication in animals and to prevent infection to humans. In this research study, we designed an in-silico multi-epitopes vaccine for B. melitensis using computational approaches. The pathogen core proteome was screened for good vaccine candidates using subtractive proteomics, reverse vaccinology and immunoinformatic tools. In total, 10 proteins: catalase; siderophore ABC transporter substrate-binding protein; pyridoxamine 5’-phosphate oxidase; superoxide dismutase; peptidylprolyl isomerase; superoxide dismutase family protein; septation protein A; hypothetical protein; binding-protein-dependent transport systems inner membrane component; and 4-hydroxy-2-oxoheptanedioate aldolase were selected for epitopes prediction. To induce cellular and antibody base immune responses, the vaccine must comprise both B and T-cells epitopes. The epitopes were next screened for antigenicity, allergic nature and water solubility and the probable antigenic, non-allergic, water-soluble and non-toxic nine epitopes were shortlisted for multi-epitopes vaccine construction. The designed vaccine construct comprises 274 amino acid long sequences having a molecular weight of 28.14 kDa and instability index of 27.62. The vaccine construct was further assessed for binding efficacy with immune cell receptors. Docking results revealed that the designed vaccine had good binding potency with selected immune cell receptors. Furthermore, vaccine-MHC-I, vaccine-MHC-II and vaccine-TLR-4 complexes were opted based on a least-binding energy score of −5.48 kcal/mol, 0.64 kcal/mol and −2.69 kcal/mol. Those selected were then energy refined and subjected to simulation studies to understand dynamic movements of the docked complexes. The docking results were further validated through MMPBSA and MMGBSA analyses. The MMPBSA calculated −235.18 kcal/mol, −206.79 kcal/mol, and −215.73 kcal/mol net binding free energy, while MMGBSA estimated −259.48 kcal/mol, −206.79 kcal/mol and −215.73 kcal/mol for TLR-4, MHC-I and MHC-II complexes, respectively. These findings were validated by water-swap and entropy calculations. Overall, the designed vaccine construct can evoke proper immune responses and the construct could be helpful for experimental researchers in formulation of a protective vaccine against the targeted pathogen for both animal and human use.

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Immunoinformatics Analysis and In-silico Design of Multi- Epitopes Vaccine Against Lassa Virus

Cited by 3 publications

References 112 publications

Designing a Recombinant Vaccine against Providencia rettgeri Using Immunoinformatics Approach

Designing a Recombinant Vaccine against Providencia rettgeri Using Immunoinformatics Approach

Computer-Aided Multi-Epitope Vaccine Design against Enterobacter xiangfangensis

Proteome-Wide Screening of Potential Vaccine Targets against Brucella melitensis

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