Aug 2026· Frontiers in Immunology· 0 citations· 87 references
TL;DR
Results demonstrated that the chimeric vaccine provides preliminary protection against a local B2 UPEC isolate, and modulating gut microbiota via faecal transplantation markedly enhances the immunogenicity and protective efficacy of vaccination, suggesting its adjuvanticity.
Abstract
Escherichia coli
remains amongst the most globally important pathogens implicated in severe clinical manifestations. The progressive rise in multidrug-resistant strains highlights the urgent need for new vaccines. Therefore, this study was designed to develop a new multi-epitope vaccine containing the most conserved epitopes across
E. coli
pathotypes. Consequently, the study aimed to investigate the immunoadjuvant role of faecal microbiota transplantation in enhancing vaccine efficacy.
Eighteen of the most conserved B-cell and T-cell epitopes of FimH, LptD, and BamA proteins were selected and included in a single construct. During the epitope selection process, HLA alleles predominant in the Iraqi population, as reported in previous studies, were used as criteria for selecting T-cell epitopes. The chimeric protein was expressed in BL21
E. coli
and purified using affinity chromatography. Vaccine cross-protective immunity and protection were tested in
in vivo
experiments. Different formulations were used in the experimental evaluation: three doses of 100 μg of purified chimeric protein, injected intraperitoneally alone or encapsulated in PLGA nanoparticles, after faecal microbiota transplantation with and without gut microbiota modulation mediated by a cocktail of antibiotics. IgG1, IL-4, INF-γ, and NLRP3 levels were measured at 30 and 75 days after the first immunisation dose. Immunised mice were challenged with the local B2 UPEC phylogroup, and protection efficacy was considered 48 h later. Finally, the histological effects of the different chimeric protein formulations on the liver were assessed.
All vaccine formulations except those after faecal microbiota transplantation without gut microbiota modulation induce significant increases in IgG1, IL-4, and INF-γ levels at different times. Only vaccination after faecal microbiota transplantation with gut microbiota modulation elicited robust NLRP3 levels at 30 and 75 days after, and this was linked to the highest reduction in bladder bacterial load by 813-fold compared to the other formulations, as well as the mildest effect on liver histological changes.
These results demonstrated that the chimeric vaccine provides preliminary protection against a local B2 UPEC isolate. Furthermore, modulating gut microbiota via faecal transplantation markedly enhances the immunogenicity and protective efficacy of vaccination, suggesting its adjuvanticity.
Toxoplasma gondii
is a significant zoonotic pathogen responsible for severe disease in immunocompromised individuals, adverse pregnancy outcomes, and substantial economic losses in the livestock industry. Given the limitations of current therapeutic strategies and vaccines, this study utilized immunoinformatics and reverse vaccinology approaches to design a multi-epitope candidate vaccine.
A total of 49 T. gondii proteins from the SAG, GRA, MIC, and ROP families were screened. Epitopes were selected based on antigenicity, immunogenicity, cytokine-inducing potential, toxicity, and allergenicity. The selected epitopes were assembled using AAY, GPGPG, and KK linkers, with the 50S ribosomal protein L7/L12 as an adjuvant. Physicochemical properties, molecular docking, molecular dynamics simulations, immune simulations, and codon optimization were subsequently evaluated.
We identified 9 cytotoxic T lymphocyte (CTL), 6 helper T lymphocyte (HTL), and 11 B-cell epitopes. The finalized 556-amino-acid construct (61.13 kDa) demonstrated favorable antigenicity (VaxiJen score: 0.6843), stability (instability index: 39.05), solubility (0.663), and hydrophilicity (GRAVY: -0.502), while maintaining safety profiles. Molecular docking and dynamics simulations confirmed robust and stable binding to TLR2 (-32.8 kcal/mol) and TLR4 (-72.37 kcal/mol). Furthermore, immune simulations predicted a strong, memory-forming humoral and cellular immune response. Codon optimization (CAI: 0.93, GC content: 56.43%) suggested high expression efficiency in
Escherichia coli
.
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
Mycobacterium tuberculosis infects one-fourth of the global population, and current challenges such as latent infections, multidrug-resistant strains, and the limited efficacy of the BCG vaccine emphasize the urgent need for next-generation vaccines. This study aimed to introduce novel vaccine candidates, immunoreactive epitopes, and a novel multi-epitope vaccine (MEV). New immunogenic targets were identified based on different characteristics, including subcellular localization, antigenicity, non-similarity to the host proteome, sequence conservation, prevalence, and B-cell and T-cell epitopes. In the next step, IFN-γ releasing immunoreactive epitopes with a high similarity to TCR-interacting epitopes were identified. The MEV was generated using shortlisted epitopes and the C-terminal fragment of Clostridium perfringens enterotoxin (CPE). Finally, the interactions of MEV epitopes with human MHC I and MHC II alleles were investigated. In the first step, a total of seven proteins with desired immunogenic properties were introduced as novel immunogenic targets. Comparison of surface-exposed proteins to 4718 immunoreactive linear B-cell epitopes of M. tuberculosis resulted in identification of 719 non-redundant immunoreactive epitopes. Finally, seven immunoreactive, IFN-γ releasing epitopes with significant homology to TCR binding epitopes were employed to design a MEV. This MEV showed desirable structural and immunogenic properties. Moreover, it revealed promising interactions with human MHC I and MHC II alleles in molecular docking. This study suggests PE/PPE proteins and TCR-recognized immunoreactive peptides as promising vaccine components against tuberculosis. In addition, the designed MEV with the C-terminal fragment of CPE may represent a potential candidate for future development as a mucosal vaccine against M. tuberculosis.
N. Noori Goodarzi, Sepideh Fereshteh, Behzad Shahbazi et al.· Genomics & Informatics· 0 citations
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.
Rhitam Biswas, Swapno Surabhi Sinha, Aditi Roy et al.· Frontiers in Bioinformatics· 0 citations
The purpose of this study was to design an epitope-based vaccine targeting the currently circulating genotypes of Newcastle disease virus (NDV) in West Africa using immunoinformatic approaches. Complete fusion protein sequences from West African NDV isolates were retrieved and aligned using MEGA11 software. Then, conserved immunodominant B cell, T helper and T cytotoxic epitopes were predicted for the construction of the vaccine candidate, NDVaxWA. Subsequently, antigenicity, allergenicity, toxicity and other physicochemical properties of NDVaxWA were evaluated using an array of in silico tools. Our findings revealed a total of 11 immuno-conserved epitopes comprising 3 BCL, 2 CTL and 6 HTL epitopes used for NDVaxWA construction. A molecular docking of Toll-like receptor-7 with the NDVaxWA indicated successful binding. An in silico immune simulation revealed robust humoral and cell mediated responses following vaccination with NDVaxWA. Taken together, NDVaxWA is a potential vaccine candidate for improved protective efficacy against the currently circulating NDV strains in West Africa.
M.B. Bello, N. Lawal· Journal of Agriculture and E...· 0 citations
Livestock production is a major contributor to food security and livelihoods worldwide. Among the parasitic diseases affecting livestock, Taenia solium infection remains a significant veterinary and public health concern, causing substantial economic losses. Therefore, effective and affordable vaccine development is required for disease prevention and improved livestock health. A multi-epitopic chimeric vaccine for livestock against Taenia spp. was computationally designed using subtractive proteomics and immuno-informatics. Antigenic proteins were selected based on antigenicity, allergenicity, and physicochemical profiling. HTL, CTL, and B-cell epitopes were predicted and assembled into a chimeric structure along with a suitable adjuvant. Structure modeling and physical characteristics, such as docking tendency with TLRs, along with the immune stimulatory response, were analysed. Molecular dynamics simulations for the TLR4-Vaccine complexes were also done for 100 ns. Immune simulation and codon optimisation predicted immunogenicity and expression potential in E. coli. 11 epitopes were identified from 3 antigenic homologous proteins. A multiepitope chimeric vaccine was designed by adding β-defensin adjuvant to mount a robust immune response. The proposed vaccine construct had 272 Amino acid residues and a molecular weight of 28.94 kDa. Upon binding with TLR4 receptors, it establishes a stable conformation, and molecular dynamics simulations also demonstrated a dynamic interplay. A multi-epitope vaccine capable of disrupting the life cycle of Taenia species across all known hosts was designed. 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
BACKGROUND
The tick-borne viruses are primarily transmitted through the bites of infected ticks. Wetland virus (WELV) is a newly identified tick-borne pathogen with no licensed vaccines and limited preventive strategies.
METHODS
In this study, a reverse vaccinology approach was used to design a multi-epitope vaccine using the conserved regions of key viral proteins of WELV.
RESULTS
Multiple sequence alignment identified 51, 31, and 5 conserved regions in the RNA-dependent RNA polymerase (R), glycoprotein (G), and nucleocapsid (N) proteins, respectively. The epitope prediction across these regions identified 784 CTL, 933 HTL, and 123 B-cell epitopes, from which antigenic, non-allergenic, and non-toxic candidates were selected for vaccine construction. The final construct was predicted to have favourable antigenicity, solubility, and physicochemical properties. Structural analysis revealed that the construct has a high percentage of random coils (49.02%). Then, the tertiary structure was refined to improve its stereochemical quality, and in the refined structure 96.2% residues were in the most favoured regions. The conformational epitope prediction identified thirteen surface-accessible B-cell epitopes. Molecular docking analysis using HADDOCK showed possible interactions with multiple Toll-like receptors with predicted binding free energies ranging from -13.1 to -15.3 kcal/mol. Codon optimization and in silico cloning were performed to insert the construct into the pET-28a(+) vector. The immune simulation analysis predicted the possibility for inducing effective response, with antibody production, T-cell activation, and long-term immunological memory.
CONCLUSION
These computational results suggest that the construct has the potential to induce effective immunity against WELV, however further experimental validations in future have to be performed in order to confirm its efficacy against the pathogen.
Kadhirmathiyan Velumani, Sarumathi Umapathi, B. Shanmugaraj· Human Immunology· 0 citations
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A new machine-learning framework aims to improve the success rate of computational protein design while moving away from results that reproduce sequences found in nature.