In silico and in vivo approaches to recombinant multi-epitope immunogen of GroEL provides efficient cross protection against S. Typhimurium, S. flexneri, and S. dysenteriae

Ardestani, Hassan; Nazarian, Shahram; Hajizadeh, Abbas; Sadeghi, Davoud; Kordbacheh, Emad

doi:10.1016/j.molimm.2022.02.013

Cited by 5 publications

(4 citation statements)

References 42 publications

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“…Moreover, multi-epitope vaccines incorporate some components with adjuvant capacity that can enhance the immunogenicity and long-lasting immune responses and reduce unwanted components that can trigger either pathological immune responses or adverse effects (25). Due to these several advantages, many trials have been performed to explore the efficacy of this new form of vaccine, where a significant activation at humoral and cellular arms of the immune system was observed against several tested pathogens such as E. coli (26), Salmonella Typhimurium and Shigella flexneri (27), and HIV-1 infection (28).…”

Section: Introductionmentioning

confidence: 99%

Mining of Marburg Virus Proteome for Designing an Epitope-Based Vaccine

Soltan

Abdulsahib²,

Amer

et al. 2022

Front. Immunol.

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Marburg virus (MARV) is one of the most harmful zoonotic viruses with deadly effects on both humans and nonhuman primates. Because of its severe outbreaks with a high rate of fatality, the world health organization put it as a risk group 4 pathogen and focused on the urgent need for the development of effective solutions against that virus. However, up to date, there is no effective vaccine against MARV in the market. In the current study, the complete proteome of MARV (seven proteins) was analyzed for the antigenicity score and the virulence or physiological role of each protein where we nominated envelope glycoprotein (Gp), Transcriptional activator (VP30), and membrane-associated protein (VP24) as the candidates for epitope prediction. Following that, a vaccine construct was designed based on CTL, HTL, and BCL epitopes of the selected protein candidates and to finalize the vaccine construct, several amino acid linkers, β-defensin adjuvant, and PADRE peptides were incorporated. The generated potential vaccine was assessed computationally for several properties such as antigenicity, allergenicity, stability, and other structural features where the outcomes of these assessments nominated this potential vaccine to be validated for its binding affinity with two molecular targets TLR-8 and TLR-4. The binding score and the stability of the vaccine-receptor complex, which was deeply studied through molecular docking-coupled dynamics simulation, supported the selection of our designed vaccine as a putative solution for MARV that should be validated through future wet-lab experiments. Here, we describe the computational approach for designing and analysis of this potential vaccine.

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Section: Introductionmentioning

confidence: 99%

Mining of Marburg Virus Proteome for Designing an Epitope-Based Vaccine

Soltan

Abdulsahib²,

Amer

et al. 2022

Front. Immunol.

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“…However, the results of docking analysis showed the binding affinity of promiscuous epitopes with different HLA alleles. An important TLR in mammals, TLR2/4 can identify lipoproteins from bacteria, viruses, fungi, and parasites [77]. Therefore, the shortlisted vaccine construct was used for the binding affinity and stability estimation of the of the vaccine and TLR4 complex.…”

Section: Discussionmentioning

confidence: 99%

Immunoinformatic-guided designing of multi-epitope vaccine construct against Brucella Suis 1300

2022

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Brucella suis mediates the transmission of brucellosis in humans and animals and a significant facultative zoonotic pathogen found in livestock. It has the capacity to survive and multiply in a phagocytic environment and to acquire resistance under hostile conditions thus becoming a threat globally. Antibiotic resistance is posing a substantial public health threat, hence there is an unmet and urgent clinical need for immune-based non-antibiotic methods to treat brucellosis. Hence, we aimed to explore the whole proteome of Brucella suis to predict antigenic proteins as a vaccine target and designed a novel chimeric vaccine (multi-epitope vaccine) through subtractive genomics-based reverse vaccinology approaches. The applied subsequent hierarchical shortlisting resulted in the identification of Multidrug efflux Resistance-nodulation-division (RND) transporter outer membrane subunit (gene BepC) that may act as a potential vaccine target. T-cell and B-cell epitopes have been predicted from target proteins using a number of immunoinformatic methods. Six MHC I, ten MHC II, and four B-cell epitopes were used to create a 324-amino-acid MEV construct, which was coupled with appropriate linkers and adjuvant. To boost the immunological response to the vaccine, the vaccine was combined with the TLR4 agonist HBHA protein. The MEV structure predicted was found to be highly antigenic, non-toxic, non-allergenic, flexible, stable, and soluble. To confirm the interactions with the receptors, a molecular docking simulation of the MEV was done using the human TLR4 (toll-like receptor 4) and HLAs. The stability and binding of the MEV-docked complexes with TLR4 were assessed using molecular dynamics (MD) simulation. Finally, MEV was reverse translated, its cDNA structure was evaluated, and then, in silico cloning into an E. coli expression host was conducted to promote maximum vaccine protein production with appropriate post-translational modifications. These comprehensive computer calculations backed up the efficacy of the suggested MEV in protecting against B. suis infections. However, more experimental validations are needed to adequately assess the vaccine candidate's potential. Highlights• Subtractive genomic analysis and reverse vaccinology for the prioritization of novel vaccine target • Examination of chimeric vaccine in terms of allergenicity, antigenicity, MHC I, II binding efficacy, and structural-based studies • Molecular docking simulation method to rank based vaccine candidate and understand their binding modes

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“…We evaluated the immune responses of full-length GroEL of S. typhi against EPEC and EHEC bacteria by encapsulation in PLGA. The increased antimicrobial resistance among EPEC and EHEC has limited the efficacy of traditionally used antibiotics 25 , 26 . This has prompted the development and use of vaccines as an alternative key strategy to overcome the drug resistance 27 .…”

Section: Discussionmentioning

confidence: 99%

“…This has prompted the development and use of vaccines as an alternative key strategy to overcome the drug resistance 27 . The HSPs elicit both humoral as well as cell-mediated immune responses with potential to develop as new generation prophylactic and therapeutic vaccines against infectious agents 20 , 25 . In this context, the immune responses of GroEL from S. typhi against EPEC and EHEC could be a strategy of choice.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of PLGA-Encapsulated Recombinant GroEL of S. typhi immune Responses Against Enterohaemorrhagic and Enteropathogenic Escherichia coli

Parvane¹,

Nazarian²,

Kordbache³

et al. 2022

AJMB

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Background: Heat Shock Proteins (HSPs) elicit humoral and cellular immune responses. Due to their high sequence homology, they can be developed as a new immunogen for cross prophylactic and vaccination effects against infectious agents such as Enteropathogenic and Enterohemorrhagic Escherichia coli (EPEC and EHEC). This study aimed to evaluate the immunogenicity and cross-protective efficacy of rGroEL of Salmonella typhi (S. typhi) encapsulated in poly lactic-co-glycolic acid (PLGA) nanoparticles against EPEC and EHEC. Methods: Recombinant GroEL was expressed in Escherichia coli (E. coli) and purified using Ni-NTA affinity chromatography. The protein was encapsulated in PLGA by the double emulsion method, and the nanoparticles were characterized physicochemically. BALB/c mice were immunized, and the efficacy of the protein to elicit immune responses was assessed. Results: Over-expression in E. coli led to corresponding 64.5 kDa protein bands in Sodium Dodecyl Sulphate-Polyacrylamide Gel Electrophoresis (SDS-PAGE). Non-ag-gregated nanoparticles had a spherical shape with a mean diameter of 194.3±3 nm and encapsulation efficiency of 89.5±2.5%. Antibody isotyping revealed that GroEL immunization induced both IgG1 and IgG2a antibodies. Moreover, immunization of the mice with recombinant GroEL protein conferred 80 and 60% protection against lethal infections by EPEC and EHEC, respectively. Furthermore, organ burden studies revealed a significant reduction in infection in the immunized mice compared to the non-immunized ones. Passive immunization with anti-GroEL sera also protected 50% of the mice against the lethal doses of EHEC and EPEC strains. Conclusion: The findings indicated that immunization of the mice with recombinant GroEL of S. typhi elicited cross-protection against other bacterial infections. This represented the immense potential of GroEL to be developed as a single vaccine against multiple pathogens.

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In silico and in vivo approaches to recombinant multi-epitope immunogen of GroEL provides efficient cross protection against S. Typhimurium, S. flexneri, and S. dysenteriae

Cited by 5 publications

References 42 publications

Mining of Marburg Virus Proteome for Designing an Epitope-Based Vaccine

Mining of Marburg Virus Proteome for Designing an Epitope-Based Vaccine

Immunoinformatic-guided designing of multi-epitope vaccine construct against Brucella Suis 1300

Evaluation of PLGA-Encapsulated Recombinant GroEL of S. typhi immune Responses Against Enterohaemorrhagic and Enteropathogenic Escherichia coli

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