المؤلفون: Morteza Hakimian, Abbas Doosti, Ali Sharifzadeh

المصدر: BMC Immunology, Vol 25, Iss 1, Pp 1-20 (2024)

مصطلحات موضوعية: Klebsiella pneumoniaee, Reverse vaccinology, In silico analysis, Multi-epitopes chimeric vaccine, Immunologic diseases. Allergy, RC581-607

الوصف: Abstract Background Due to antibiotic resistance, the Klebsiella genus is linked to morbidity and death, necessitating the development of a universally protective vaccine against Klebsiella pathogens. Methods Core sequence analysis prioritized non-redundant host molecules and expected lipid bilayer peptides from fully sequenced Klebsiella genomes. These proteins were refined to identify epitopes, examining their immunogenicity, toxicity, solubility, and interaction with MHC alleles. Epitopes were linked to CPG ODN C274 via EAAAK, HEYGAEALERAG, and GGGS linkers to enhance immunological responses. The vaccine’s tertiary structure was modelled and docked with MHC-I and MHC-II. Results Fifty-five proteins were recognized in the Vaxign collection as having remarkable features. Twenty-three proteins with potential pathogenicity were then identified. Eight options for vaccines emerged after the immunogenicity of proteins was examined. The best antigens were three proteins: MrkD, Iron-regulated lipid membrane polypeptides, and RmpA. These compounds were selected for their sensitivity. The structural protein sequences of K. pneumoniae were utilized to identify seven CTL epitopes, seven HTL epitopes, and seven LBL epitopes, respectively. The produced immunization displayed a stable contact with the receptors, based on molecular dynamic simulations lasting 250 nanoseconds. Intermolecular binding free energies also indicated the dominance of the van der Waals and electrostatic energies. Conclusion In summary, the results of this study might help scientists develop a novel vaccine to prevent K. pneumoniae infections.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1471-2172Test

الوصول الحر: https://doaj.org/article/fc43fdacc79048efa6d5c3472754b20bTest

المؤلفون: Marta Filipa Silva, Gonçalo Pereira, Luísa Mateus, Luís Lopes da Costa, Elisabete Silva

المصدر: BMC Veterinary Research, Vol 20, Iss 1, Pp 1-11 (2024)

مصطلحات موضوعية: Bovine genital campylobacteriosis, Campylobacter fetus subsp. venerealis, Reverse vaccinology, Vaccine, Veterinary medicine, SF600-1100

الوصف: Abstract Background Bovine Genital Campylobacteriosis (BGC), a worldwide distributed venereal disease caused by Campylobacter fetus subsp. venerealis (Cfv), has a relevant negative economic impact in cattle herds. The control of BGC is hampered by the inexistence of globally available effective vaccines. The present in silico study aimed to develop a multi-epitope vaccine candidate against Cfv through reverse vaccinology. Results The analysis of Cfv strain NCTC 10354 proteome allowed the identification of 9 proteins suitable for vaccine development. From these, an outer membrane protein, OmpA, and a flagellar protein, FliK, were selected for prediction of B-cell and T-cell epitopes. The top-ranked epitopes conservancy was assessed in 31 Cfv strains. The selected epitopes were integrated to form a multi-epitope fragment of 241 amino acids, which included 2 epitopes from OmpA and 13 epitopes from FliK linked by GPGPG linkers and connected to the cholera toxin subunit B by an EAAAK linker. The vaccine candidate was predicted to be antigenic, non-toxic, non-allergenic, and soluble upon overexpression. The protein structure was predicted and optimized, and the sequence was successfully cloned in silico into a plasmid vector. Additionally, immunological simulations demonstrated the vaccine candidate’s ability to stimulate an immune response. Conclusions This study developed a novel vaccine candidate suitable for further in vitro and in vivo experimental validation, which may become a useful tool for the control of BGC.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1746-6148Test

الوصول الحر: https://doaj.org/article/bb251cd6e3234fc6b8d75ef83ea10598Test

المؤلفون: Peng Chao, Xueqin Zhang, Lei Zhang, Aiping Yang, Yong Wang, Xiaoyang Chen

المصدر: Scientific Reports, Vol 14, Iss 1, Pp 1-15 (2024)

مصطلحات موضوعية: Immunoinformatics, Reverse vaccinology, Pan-genome, Multi-epitope vaccine, Medicine, Science

الوصف: Abstract Streptococcus gallolyticus is a non-motile, gram-positive bacterium that causes infective endocarditis. S. gallolyticus has developed resistance to existing antibiotics, and no vaccine is currently available. Therefore, it is essential to develop an effective S. gallolyticus vaccine. Core proteomics was used in this study together with subtractive proteomics and reverse vaccinology approach to find antigenic proteins that could be utilized for the design of the S. gallolyticus multi-epitope vaccine. The pipeline identified two antigenic proteins as potential vaccine targets: penicillin-binding protein and the ATP synthase subunit. T and B cell epitopes from the specific proteins were forecasted employing several immunoinformatics and bioinformatics resources. A vaccine (360 amino acids) was created using a combination of seven cytotoxic T cell lymphocyte (CTL), three helper T cell lymphocyte (HTL), and five linear B cell lymphocyte (LBL) epitopes. To increase immune responses, the vaccine was paired with a cholera enterotoxin subunit B (CTB) adjuvant. The developed vaccine was highly antigenic, non-allergenic, and stable for human use. The vaccine's binding affinity and molecular interactions with the human immunological receptor TLR4 were studied using molecular mechanics/generalized Born surface area (MMGBSA), molecular docking, and molecular dynamic (MD) simulation analyses. Escherichia coli (strain K12) plasmid vector pET-28a ( +) was used to examine the ability of the vaccine to be expressed. According to the outcomes of these computer experiments, the vaccine is quite promising in terms of developing a protective immunity against diseases. However, in vitro and animal research are required to validate our findings.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2045-2322Test

الوصول الحر: https://doaj.org/article/057b73d582f546029a1a1945c0238a44Test

المؤلفون: Alaa Karkashan

المصدر: Frontiers in Immunology, Vol 15 (2024)

مصطلحات موضوعية: computer-assisted vaccine designing, reverse vaccinology, immunoinformatics, molecular docking, MD simulation, Immunologic diseases. Allergy, RC581-607

الوصف: Emerging infectious diseases represent a significant threat to global health, with West Nile virus (WNV) being a prominent example due to its potential to cause severe neurological disorders alongside mild feverish conditions. Particularly prevalent in the continental United States, WNV has emerged as a global concern, with outbreaks indicating the urgent need for effective prophylactic measures. The current problem is that the absence of a commercial vaccine against WNV highlights a critical gap in preventive strategies against WNV. This study aims to address this gap by proposing a novel, multivalent vaccine designed using immunoinformatics approaches to elicit comprehensive humoral and cellular immune responses against WNV. The objective of the study is to provide a theoretical framework for experimental scientists to formulate of vaccine against WNV and tackle the current problem by generating an immune response inside the host. The research employs reverse vaccinology and subtractive proteomics methodologies to identify NP_041724.2 polyprotein and YP_009164950.1 truncated flavivirus polyprotein NS1 as the prime antigens. The selection process for epitopes focused on B and T-cell reactivity, antigenicity, water solubility, and non-allergenic properties, prioritizing candidates with the potential for broad immunogenicity and safety. The designed vaccine construct integrates these epitopes, connected via GPGPG linkers, and supplemented with an adjuvant with the help of another linker EAAAK, to enhance immunogenicity. Preliminary computational analyses suggest that the proposed vaccine could achieve near-universal coverage, effectively targeting approximately 99.74% of the global population, with perfect coverage in specific regions such as Sweden and Finland. Molecular docking and immune simulation studies further validate the potential efficacy of the vaccine, indicating strong binding affinity with toll-like receptor 3 (TLR-3) and promising immune response profiles, including significant antibody-mediated and cellular responses. These findings present the vaccine construct as a viable candidate for further development and testing. While the theoretical and computational results are promising, advancing from in-silico predictions to a tangible vaccine requires comprehensive laboratory validation. This next step is essential to confirm the vaccine’s efficacy and safety in eliciting an immune response against WNV. Through this study, we propose a novel approach to vaccine development against WNV and contribute to the broader field of immunoinformatics, showcasing the potential to accelerate the design of effective vaccines against emerging viral threats. The journey from hypothesis to practical solution embodies the interdisciplinary collaboration essential for modern infectious disease management and prevention strategies.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fimmu.2024.1395870/fullTest; https://doaj.org/toc/1664-3224Test

الوصول الحر: https://doaj.org/article/ca27bfd161634e6aa8bd60ebcbf36d49Test

المؤلفون: Mansoor Kodori, Jafar Amani, Ali Ahmadi

المصدر: BMC Infectious Diseases, Vol 23, Iss 1, Pp 1-15 (2023)

مصطلحات موضوعية: Coxiella burnetii, Reverse vaccinology, Immunogenic proteins, Q Fever, Infectious and parasitic diseases, RC109-216

الوصف: Abstract Background Coxiella burnetii, an intracellular pathogen, serves as the causative agent of zoonotic Q fever. This pathogen presents a significant threat due to its potential for airborne transmission, environmental persistence, and pathogenicity. The current whole-cell vaccine (WCV) utilized in Australia to combat Q fever exhibits notable limitations, including severe adverse reactions and limited regulatory approval for human use. This research employed the reverse vaccinology (RV) approach to uncover antigenic proteins and epitopes of C. burnetii, facilitating the development of more potent vaccine candidates. Methods The potential immunogenic proteins derived from C. burnetii RSA493/Nine Mile phase I (NMI) were extracted through manual, automated RV, and virulence factor database (VFDB) methods. Web tools and bioinformatics were used to evaluate physiochemical attributes, subcellular localization, antigenicity, allergenicity, human homology, B-cell epitopes, MHC I and II binding ratios, functional class scores, adhesion probabilities, protein-protein interactions, and molecular docking. Results Out of the 1850 proteins encoded by RSA493/NMI, a subset of 178 demonstrated the potential for surface or membrane localization. Following a series of analytical iterations, 14 putative immunogenic proteins emerged. This collection included nine proteins (57.1%) intricately involved in cell wall/membrane/envelope biogenesis processes (CBU_0197 (Q83EW1), CBU_0311 (Q83EK8), CBU_0489 (Q83E43), CBU_0939 (Q83D08), CBU_1190 (P39917), CBU_1829 (Q83AQ2), CBU_1412 (Q83BU0), CBU_1414 (Q83BT8), and CBU_1600 (Q83BB2)). The CBU_1627 (Q83B86 ) (7.1%) implicated in intracellular trafficking, secretion, and vesicular transport, and CBU_0092 (Q83F57) (7.1%) contributing to cell division. Additionally, three proteins (21.4%) displayed uncharacterized functions (CBU_0736 (Q83DJ4), CBU_1095 (Q83CL9), and CBU_2079 (Q83A32)). The congruent results obtained from molecular docking and immune response stimulation lend support to the inclusion of all 14 putative proteins as potential vaccine candidates. Notably, seven proteins with well-defined functions stand out among these candidates. Conclusions The outcomes of this study introduce promising proteins and epitopes for the forthcoming formulation of subunit vaccines against Q fever, with a primary emphasis on cellular processes and the virulence factors of C. burnetii.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1471-2334Test

الوصول الحر: https://doaj.org/article/a31f4ef8b0bd4a2b93d47d6451d151c4Test

المؤلفون: Niloofar Sadat Tabibpour, Abbas Doosti, Ali Sharifzadeh

المصدر: BMC Immunology, Vol 24, Iss 1, Pp 1-18 (2023)

مصطلحات موضوعية: Multi-epitope polypeptide, Reverse vaccinology, Acinetobacter baumannii, Immunologic diseases. Allergy, RC581-607

الوصف: Abstract Multi-epitope polypeptide vaccines, a fusion protein, often have a string-of-beads system composed of various specific peptide epitopes, potential adjuvants, and linkers. When choosing the sequence of various segments and linkers, many alternatives are available. These variables can influence the vaccine’s effectiveness through their effects on physicochemical properties and polypeptide tertiary structure. The most conserved antigens were discovered using BLASTn. To forecast the proteins’ subcellular distribution, PSORTb 3.0.2 was used. Vaxign was used for the preliminary screening and antigenicity assessment. Protein solubility was also predicted using the ccSOL omics. Using PRED-TMBB, it was anticipated that the protein would localize across membranes. The IEDB and BepiPred-2.0 databases were used to predict the immunogenicity of B cell epitopes. A multi-epitope construct was developed and analyzed to evaluate. Twenty epitopes from A. baumannii’s outer membrane protein (omp) were included in the vaccination. TLR4 agonist explosibility was investigated. The physicochemical characteristics, secondary and tertiary structures, and B-cell epitopes of vaccine constructs were assessed. Additionally, docking and MD experiments were used to examine the relationship between TLR4 and its agonist. Thirteen antigens were discovered, and eight of the 13 chosen proteins were predicted to be surface proteins. The 34 kDa outer membrane protein, Omp38, Omp W, CarO, putative porin, OmpA, were chosen as having the right antigenicity (≥0.5). FhuE and CdiA were eliminated from further study because of their low antigenicity. The vaccine design was developed by combining the most effective 10 B-cell and 10 MHC-I/MHCII combined coverage epitopes. The molecular formula of the vaccine was determined to be C1718H2615N507O630S17. The vaccine form has a molecular weight of 40,996.70 Da and 47 negatively charged residues (Asp + Glu), whereas 28 positively charged residues (Arg + Lys). The estimated half-life was 7.2 hours (mammalian reticulocytes, in vitro), > 20 hours (yeast, in vivo) and > 10 hours (Escherichia coli, in vivo) for the vaccine. The multi-epitope vaccine insertion is carried via the expression vector pcDNA3.1 (+). The multi-epitope vaccine may stimulate humoral and cellular immune responses, according to our findings, and it may be a candidate for an A. baumannii vaccine.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1471-2172Test

الوصول الحر: https://doaj.org/article/52ed2ee96bb94a20b60874e521c60c2eTest

المؤلفون: Mahamudul Hasan, Shakil Ahmed, Md. Imranuzzaman, Rezaul Bari, Shiplu Roy, Md. Mahadi Hasan, Md. Mukthar Mia

المصدر: Journal of Genetic Engineering and Biotechnology, Vol 22, Iss 3, Pp 100398- (2024)

مصطلحات موضوعية: Avian rotavirus, Reoviridae, Reverse vaccinology, Peptide vaccine, Molecular docking, Biotechnology, TP248.13-248.65, Genetics, QH426-470

الوصف: Background: Enteric avian rotavirus (ARV) is the etiological agent of several health problems that pose a global threat to commercial chickens. Therefore, to avoid these widespread epidemics and high mortality rates, only vaccine and strict biosecurity are required. Method: The present study employs computational techniques to design a unique multi-epitope-based vaccine candidate that successfully activates immune cells against the ARV by combining adjuvant, linker, and B and T-cell epitopes. Starting, homologous sequences in the various ARV serotypes were revealed in the NCBI BLAST database, and then the two surface proteins (VP4 and VP7) of the ARV were retrieved from the UniprotKB database. The Clustal Omega server was then used to identify the conserved regions among the homologous sequences, and the B and T-cell epitopes were predicted using IEDB servers. Then, superior epitopes—2 MHC-1 epitopes, 2 MHC-2 epitopes, and 3B-cell epitopes—were combined with various adjuvants to create a total of four unique vaccine candidates. Afterward, the designed vaccine candidates underwent computational validation to assess their antigenicity, allergenicity, and stability. The vaccine candidate (V2) that demonstrated non-antigenicity, a high VaxiJen score, and non-allergenicity was ultimately chosen for molecular docking and dynamic simulation. Results: Although the V2 and V4 vaccine candidates were highly immunogenic, V2 had a higher solubility rate. The predicted values of the aliphatic index and GRAVY value were 30.4 and 0.417, respectively. In terms of binding energy, V2 outperformed V4. Being successfully docked with TLRs, V2 was praised as the finest. After adaptation, the sequence’s 50.73 % GC content outside of the BglII or ApaI restriction sites indicated that it was equivalently safe to clone. The chosen sequence was then inserted into the pET28a(+) vector within the BglII and ApaI restriction sites. This resulted in a final clone that was 4914 base pairs long, with the inserted sequence accounting for 478 bp and the vector accounting for the remainder. Conclusions: The immune-mediated simulation results for the selected vaccine construct showed significant response; thus, the study confirmed that the selected V2 vaccine candidate could enhance the immune response against ARV.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S1687157X2400101XTest; https://doaj.org/toc/1687-157XTest

الوصول الحر: https://doaj.org/article/97427a8b7be848939e30174b20c29277Test

المؤلفون: Cena Aram, Parsa Alijanizadeh, Kiarash Saleki, Leila Karami

المصدر: Biochemistry and Biophysics Reports, Vol 39, Iss , Pp 101745- (2024)

مصطلحات موضوعية: Immunoinformatics, Multi-epitope, SARS-CoV, Reverse vaccinology, SARS-CoV-2, Computational immunology, Biology (General), QH301-705.5, Biochemistry, QD415-436

الوصف: The oldest human coronavirus that started pandemics is severe acute respiratory syndrome virus (SARS-CoV). While SARS-CoV was eradicated, its new version, SARS-CoV2, caused the global pandemic of COVID-19. Evidence highlights the harmful events orchestrated by these viruses are mediated by Spike (S)P protein. Experimental epitopes of the S protein which were overlapping and ancestral between SARS-CoV and SARS-CoV-2 were obtained from the immune epitopes database (IEDB). The epitopes were then assembled in combination with a 50 S ribosomal protein L7/L12 adjuvant, a Mycobacterium tuberculosis-derived element and mediator of dendritic cells (DCs) and toll-like receptor 4 (TLR4). The immunogenic sequence was modeled by the GalaxyWeb server. After the improvement and validation of the protein structure, the physico-chemical properties and immune simulation were performed. To investigate the interaction with TLR3/4, Molecular Dynamics Simulation (MDS) was used. By merging the 17 B- and T-lymphocyte (HTL/CTL) epitopes, the vaccine sequence was created. Also, the Ramachandran plot presented that most of the residues were located in the most favorable and allowed areas. Moreover, SnapGene was successful in cloning the DNA sequence linked to our vaccine in the intended plasmid. A sequence was inserted between the XhoI and SacI position of the pET-28a (+) vector, and simulating the agarose gel revealed the existence of the inserted gene in the cloned plasmid with SARS vaccine (SARSV) construct, which has a 6565 bp in length overall. In terms of cytokines/IgG response, immunological simulation revealed a strong immune response. The stabilized vaccine showed strong interactions with TLR3/4, according to Molecular Dynamics Simulation (MDS) analysis. The present ancestral vaccine targets common sequences which seem to be valuable targets even for the new variant SARS-CoV-2.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2405580824001092Test; https://doaj.org/toc/2405-5808Test

الوصول الحر: https://doaj.org/article/b1d36de4b7cb4ff4a88097718bf5b639Test

المؤلفون: A. G. Galeeva, N. I. Khammadov, M. A. Efimova

المصدر: Проблемы особо опасных инфекций, Vol 0, Iss 3, Pp 66-72 (2023)

مصطلحات موضوعية: rabies virus, recombinant vaccines, bioinformatics analysis, reverse vaccinology, Infectious and parasitic diseases, RC109-216

الوصف: There is a need to develop a new generation of anti-rabies vaccines that provide a protective level of antibodies after a single injection. Prospects for solving this problem are opened by the latest developments in the field of “reverse vaccinology”. The main parameter that determines the effectiveness of recombinant vaccines is the design of the antigen-coding sequence. In this regard, the aim of the work was to conduct a bioinformatic analysis of rabies virus (Rabies lyssavirus, Rhabdoviridae) peptides to identify immunogenic epitopes.Materials and methods. Analysis of 5 candidate protein sequences of more than 100 strains and epizootic isolates of the rabies virus was performed using standard in silico prediction methods using Immune Epitope Database (IEDB) (NIH, USA).Results and discussion. As a result of the analysis of primary amino acid sequences, carried out using the most commonly used bioinformatics tools, the number of immunogenic epitopes and the types of immune response detected (T- and B-cell epitopes, class I MHCbinding epitopes) were established for viral proteins: glycoprotein (G), nucleoprotein (N), phosphoprotein (P), matrix protein (M), RNA-dependent RNA polymerase (L). In the amino acid structure of these proteins, N- and O-glycosylation sites, signal peptides, and transmembrane domains were additionally identified. In order to predict the safety and efficacy of these proteins as components of recombinant vaccines, an in silico assessment of their physicochemical properties was carried out. Despite the fact that the predominant number of epitopes is concentrated in the structure of the glycoprotein, the epitopes of other proteins, ranging according to the level of antigenicity and conservatism, may also be of interest as components of preventive drugs or diagnostics. The presented data can be used in the design of the insert during the construction of a candidate virus-vector vaccine or control positive samples in diagnostic methods based on the indication of viral genome fragments.

وصف الملف: electronic resource

العلاقة: https://journal.microbe.ru/jour/article/view/1856Test; https://doaj.org/toc/0370-1069Test; https://doaj.org/toc/2658-719XTest

الوصول الحر: https://doaj.org/article/a47a4afec35a48d6a19f1d4d7cdd28f4Test

المؤلفون: Sudais Rahman, Chien-Chun Chiou, Shabir Ahmad, Zia Ul Islam, Tetsuya Tanaka, Abdulaziz Alouffi, Chien-Chin Chen, Mashal M. Almutairi, Abid Ali

المصدر: Bioengineering, Vol 11, Iss 5, p 505 (2024)

مصطلحات موضوعية: Bartonella henselae, subtractive proteome analysis, reverse vaccinology, immune simulation, in silico cloning, Technology, Biology (General), QH301-705.5

الوصف: Bartonella henselae is a Gram-negative bacterium causing a variety of clinical symptoms, ranging from cat-scratch disease to severe systemic infections, and it is primarily transmitted by infected fleas. Its status as an emerging zoonotic pathogen and its capacity to persist within host erythrocytes and endothelial cells emphasize its clinical significance. Despite progress in understanding its pathogenesis, limited knowledge exists about the virulence factors and regulatory mechanisms specific to the B. henselae strain Houston-1. Exploring these aspects is crucial for targeted therapeutic strategies against this versatile pathogen. Using reverse-vaccinology-based subtractive proteomics, this research aimed to identify the most antigenic proteins for formulating a multi-epitope vaccine against the B. henselae strain Houston-1. One crucial virulent and antigenic protein, the PAS domain-containing sensor histidine kinase protein, was identified. Subsequently, the identification of B-cell and T-cell epitopes for the specified protein was carried out and the evaluated epitopes were checked for their antigenicity, allergenicity, solubility, MHC binding capability, and toxicity. The filtered epitopes were merged using linkers and an adjuvant to create a multi-epitope vaccine construct. The structure was then refined, with 92.3% of amino acids falling within the allowed regions. Docking of the human receptor (TLR4) with the vaccine construct was performed and demonstrated a binding energy of −1047.2 Kcal/mol with more interactions. Molecular dynamic simulations confirmed the stability of this docked complex, emphasizing the conformation and interactions between the molecules. Further experimental validation is necessary to evaluate its effectiveness against B. henselae.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2306-5354/11/5/505Test; https://doaj.org/toc/2306-5354Test

الوصول الحر: https://doaj.org/article/b3f2fe3121e9452ea10d46e1a1fa6f84Test