Vc7 has been identified as a structurally stable and highly immunogenic construct, suggesting its potential as a universal multi-epitope vaccine candidate for the prevention of brucellosis.
Abstract
Introduction Brucella spp. are Gram-negative bacteria accountable for brucellosis in immunocompromised individuals and livestock. Due to the slow-growing latent phenotype, current antibiotics are insufficient to treat the infection. The lack of an approved vaccine for human use against this pathogen represents a significant public health concern and indicates the urgent need for novel prophylactic interventions. Methodology In this study, the reverse vaccinology method was combined with pan-genome analysis to identify potential vaccine targets. Proteins have been screened for antigenicity, solubility, immunogenicity, and subcellular localization. B cell and T cell epitopes exhibiting high immunogenicity and solubility have been identified. Multi-epitope vaccine constructs have been evaluated and further analyzed depending on their physicochemical properties. Molecular docking, conformational dynamics, in silico cloning, and immune simulations were conducted to identify the optimal vaccine candidate. Results Four proteins, trigger factor, outer membrane protein assembly factor BamA, urease subunit beta (UreB), and urease subunit alpha (UreC1) were considered for potential vaccine targets. A total of 26 B cell and 97 T cell epitopes with notable immunogenicity and solubility have been shortlisted. Twelve multi-epitope vaccine constructs were generated, among which Vc7 has been chosen based on structural and physicochemical properties. Molecular docking analysis revealed a good correlation with 2FSE and 2Z65, which were further analyzed to reveal that Vc7 exhibited stronger binding affinity (−135.24 kcal/mol) towards 2FSE, mediated by hydrophobic contacts, salt bridges, and intermolecular hydrogen bonds, making it the ideal vaccine complex and validated through a 150 ns molecular dynamics simulation. In silico cloning established construct compatibility, and immune simulation confirmed Vc7’s potential to elicit T cell, B cell, antibody, and cytokine-mediated responses. Conclusion Vc7 has been identified as a structurally stable and highly immunogenic construct, suggesting its potential as a universal multi-epitope vaccine candidate for the prevention of brucellosis.
The rationally designed multi-epitope vaccine demonstrates robust theoretical potential to elicit comprehensive, long-lasting immunity in humans, although its safety and effectiveness require additional experimental validation.
Chenchen Yi, Yu Shen, Ye Luo et al.· Frontiers in Cellular and In...· 0 citations
Among infectious diseases, tuberculosis is the biggest cause of death worldwide. Thus, controlling TB, a global epidemic, is a major public health concern on a worldwide scale. According to epidemiological modelling, a new vaccination that can prevent TB, especially in adults and adolescents, is necessary to control the disease’s spread, even while medication therapies for the disease are still improving. The development of novel vaccines with broader applicability and improved, long-lasting effectiveness becomes increasingly crucial as strains resistant to various drugs emerge. This work designed a multi-epitope subunit vaccine (MESV) candidateusing immunoinformatic approaches that targets five virulence-associated proteins, Rv0227c, Rv0584, Lipoprotein LprA, Phospholipase C, and Antigen 85 C. Antigenicity, non-allergenicity, and non-toxicity were the criteria used to identify and filter potential CTL, HTL, and B-cell epitopes. High-affinity epitopes connected with suitable spacers and an adjuvant for improved immunogenicity were included in the carried-out vaccine formulation. Validation and structural modelling verified the MESV’s quality and stability. TLR2 and TLR4 receptors have strong interactions, which were further demonstrated through molecular docking, and molecular dynamics simulations showed low fluctuations and good structural stability. Further, the MMPBSA analysis was introduced to determine the binding affinity of the vaccine construct, and a more pronounced binding affinity was established by the designed vaccine with TLR4. Increased cytokine release, memory cell development, and the developed MESV candidateare viable options warranting further experimental validation, as it may elicit potent humoral and cellular immune responses against M. tuberculosis.
Swagat Ranjan Maharana, S. Khan, Kiran Mahapatra et al.· Scientific Reports· 0 citations
The Middle East is a significant hotspot for human hydatidosis caused by Echinococcus granulosus, a complex multi-stage pathogen exhibiting antigenic variation with diverse epitopes. Multi-epitope vaccines, designed using immunoinformatics, represent a promising approach to effectively control this challenging parasite. A total of 1150 secreted, non-toxic, antigenic proteins were obtained from database and analyzed for their immunogenic potential, leading to the identification of 1024 CTL, 80 HTL, and 172 LBL prioritized epitopes, which were then ranked and clustered to prefer the most immunogenicity epitopes to include in novel vaccine construct. The chosen Construct (Con2) was modified for dual-plasmid insertion, facilitating the expression of three different vaccine constructs which were predicted by C-ImmSim to stimulate robust IFN-γ/IL-2 production and enhance IgM/IgG antibody secretion. Utilizing in silico, next-generation vaccine design, we propose several vaccine candidates that warrant further validation through in vitro laboratory testing and in vivo studies to assess their immunological efficacy.
Dania Skhal, S. Al Nahhas, Osama Skhal et al.· Scientific Reports· 0 citations
Vibrio alginolyticus is an opportunistic marine pathogen that causes severe vibriosis in aquatic animals and occasionally in humans, leading to substantial economic losses in aquaculture. Despite progress in antimicrobial therapy, the emergence of multidrug-resistant (MDR) strains and the lack of effective vaccines have emphasized the need for novel approaches. The objective of this study was to identify and assess vaccine candidates in V. alginolyticus ATCC 17749 using an integrative strategy that integrates reverse vaccinology and immune-informatics. The complete proteome of V. alginolyticus ATCC 17749 was retrieved from NCBI databases, and computational pipelines were used to predict subcellular localization, transmembrane topology, and antigenicity. Surface-exposed, non-allergenic and non-toxic outer membrane and secretory proteins with high antigenicity scores were selected for epitope prediction. Cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL), and B-cell epitopes were identified through NetMHCpan 4.1, IEDB, and ABCpred, respectively. Robust humoral and cellular immune responses were predicted by immune simulation. The target proteins were docked with TLR2 and TLR4 using HDOCK, and the simulation was performed using the iMODS server for the highest-scoring docking complex for each receptor. In silico cloning to express the target protein was performed using the SnapGene tool. This integrated computational vaccinology approach reliably identifies promising antigenic targets for V. alginolyticus, providing a foundation for the rational development of next-generation polyvalent vaccines against Vibrio infections in aquaculture and related fields.
Y. Kumar, Anusha Suresh, Vandana Rajshree et al.· Journal of Pure and Applied...· 0 citations
Brucellosis remains one of the most prevalent zoonotic diseases worldwide, causing substantial economic losses and significant human morbidity. Despite decades of research, no licensed human vaccine against Brucella infection exists, and current veterinary vaccines exhibit considerable safety limitations including residual virulence, pregnancy complications, and diagnostic interference. Here we report the development of a multi-epitope messenger RNA (mRNA) vaccine candidate targeting Brucella melitensis, the most pathogenic species responsible for human brucellosis. Using an integrated immunoinformatics pipeline, we screened ten outer membrane proteins (OMPs) and identified Omp25, Omp31, and BP26 as the most immunodominant antigens. A fusion construct incorporating 24 HLA class I and 31 HLA class II predicted epitopes achieved 87.3% global HLA population coverage. Codon optimization improved the codon adaptation index from 0.55 to 0.93. Molecular dynamics simulations over 200 ns confirmed structural stability of the vaccine-TLR4 complex, with a binding free energy of -65.7 kcal/mol. In vitro assays demonstrated robust Th1-biased immune activation, with IFN-gamma reaching 125.6 pg/mL. In a BALB/c mouse challenge model, the mRNA vaccine conferred 80.0% protection, comparable to the live-attenuated S19 vaccine (92.3%) but without associated safety risks. These findings establish a promising platform for Brucella vaccine development warranting further evaluation in large animal models and human clinical trials.
Zhiheng Dong, Sha Li, Jiarong Guo et al.· Research in Veterinary Scien...· 0 citations
The computationally designed vaccine meets all essential criteria and has shown immense potential to be an effective vaccine through in silico analysis, however, additional In-vitro and In-vivo validations are imperative.
Swati Sharma, Prerna Verma, A. K. Keshri et al.· Discover Life· 0 citations
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