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Results for “Multi-epitope vaccine”

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PubMed2026

Integrated immunoinformatics for the design of novel multi-epitope vaccine and identification of new drug targets against Stenotrophomonas maltophilia, a multidrug-resistant superbug.

BACKGROUND: Stenotrophomonas maltophilia is a multidrug-resistant opportunistic pathogen causing severe hospital-acquired infections, especially in immunocompromised patients. The absence of an effective vaccine and rising antibiotic resistance underscore the need for novel interventions. This study employed an integrated reverse vaccinology and computational analyses to identify new immunogenic targets, design a multi-epitope vaccine (MEV), and propose potential drug targets. METHODS: A comprehensive immunoinformatics pipeline was employed to assess antigenicity, allergenicity, human similarity, and physicochemical properties of S. maltophilia proteins. Both B- and T-cell epitopes were screened; however, only the top B-cell epitopes were selected for MEV construction, given the extracellular nature of S. maltophilia. MEV-TLR interactions were analyzed through molecular docking and dynamics simulations. In parallel, cytoplasmic proteins were screened via a subtractive genomics approach to identify essential, non-human homologous, and non-microbiome-similar proteins, which were further evaluated for druggability and interaction networks to propose novel therapeutic targets. RESULTS: From a total of 4111 proteins, seven potential immunogenic targets were identified: GspD (WP_108270537.1), FhuE (WP_049451370.1), fimbrial protein (WP_012479122.1), TonB-dependent receptor (WP_169448402.1), TolC family protein (WP_108270106.1), autotransporter beta-barrel OMP (WP_169448945.1), and a hypothetical protein (WP_005407892.1). Subsequently, an MEV was designed using five immunogenic epitopes derived from four of these targets: WP_005407892.1 (ADQDSSNM), WP_049451370.1 (SGKAEQ and GEESKTPS), WP_108270537.1 (GVTSTQSDSERT), and WP_169448945.1 (RELGGDRNE). Molecular docking and molecular dynamics simulations demonstrated strong, stable, and feasible interactions between the MEV and TLR-2 and TLR-4 receptors. Moreover, nine novel drug targets were predicted for S. maltophilia, providing new therapeutic insights. CONCLUSION: The designed MEV and identified immunogenic targets represent promising vaccine candidates against S. maltophilia. Further in vitro and in vivo studies are essential to confirm their safety, immunogenicity, and protective efficacy. Additionally, subtractive genomics analysis revealed nine novel, non-homologous drug targets, offering safer and more specific therapeutic avenues.

Drug targets↗
PubMed2026

An immunoinformatics-based multi-epitope vaccine candidate confers cross-protection against two Actinobacillus pleuropneumoniae serovars.

Porcine contagious pleuropneumonia (PCP) is caused by Actinobacillus pleuropneumoniae (APP) and inflicts heavy economic losses on the swine industry. However, existing inactivated vaccines provide limited cross-protection, highlighting the need for improved vaccine strategies. In this study, we combined pangenome analysis with subtractive proteomics to screen the APP core genome and identified 11 potential antigens. Seven of them showed immunoreactivity by ELISA and Western blotting. These antigens, together with the ApxI-III toxins, were used for T and B cell epitope prediction. On this basis, a multi-epitope fusion protein MVAPP was constructed. In silico molecular docking with swine immune receptors and immune simulations suggested that MVAPP has the potential to induce immune responses. In the mouse model, that MVAPP elicited specific antibody responses, shifted the splenic T-cell subset distribution toward CD4+ T cells, and provided partial protection against challenge with strains from two serovars. In conclusion, MVAPP represents a potential multi-epitope vaccine candidate for further development against APP.

Animals↗
PubMed2026

Comparative Genomics-Guided Epitope Prioritization and in Silico Design of a Multi-Epitope DNA Vaccine Candidate Against Megalocytivirus pagrus 1.

Megalocytivirus pagrus 1 infection is a World Organisation for Animal Health-listed aquatic animal disease caused by a virus species comprising the RSIV, ISKNV, and TRBIV genogroups. Here, we integrated comparative genomics and immunoinformatics to prioritize a multi-epitope protein construct, pMEV, and to design a DNA vaccine candidate encoding it, with emphasis on RSIV-type infection relevant to rock bream aquaculture. Analysis of 61 complete genomes identified 28 core gene clusters, from which myristoylated membrane protein (MMP) and major capsid protein (MCP) were prioritized as source antigens for epitope screening. Four cytotoxic T-cell, five helper T-cell, and five linear B-cell epitope candidates were selected based on sequence-based screening and exploratory peptide-MHC docking. The selected epitopes were assembled with rock bream beta-defensin-3, PADRE, and peptide linkers to generate the 283-aa pMEV construct. Sequence-based physicochemical analyses indicated properties relevant to subsequent structural and expression-based evaluation, while computationally refined structural modeling identified nine putative conformational B-cell epitope regions. TLR3 docking, normal mode analysis, and a 200-ns molecular dynamics simulation characterized the structural behavior of the selected computational complex without inferring receptor activation. C-ImmSim further generated model-dependent generic humoral and helper T-cell-associated response patterns within a mammalian-based simulation framework. Finally, the pMEV coding sequence was codon-optimized and incorporated into an in silico pcDNA3.1(+)-based DNA vaccine design. Collectively, this study provides a comparative genomics-guided framework for prioritizing an experimentally testable multi-epitope DNA vaccine candidate against M. pagrus 1, while construct expression, immunogenicity, and protective efficacy remain to be evaluated experimentally.

Animals↗
PubMed2025

A pan-beta-coronavirus vaccine bearing conserved and asymptomatic B- and T-cell epitopes protects against highly pathogenic Delta and highly transmissible Omicron SARS-CoV-2 variants.

Over the last five years of the COVID-19 pandemic, the repetitive mutations and deletions in the SARS-CoV-2 genome, primarily targeting the Spike gene, resulted in the emergence of multiple viral variants and sub-variants. The non-updated mismatched Spike-based sub-unit vaccines are less effective due to the ability of these SARS-CoV-2 variants and sub-variants to evade vaccine-induced humoral immunity. To reduce reliance on neutralizing antibodies and prevent potential mismatches between circulating variants, sub-variants, and the vaccines, we have identified highly conserved Spike and non-Spike viral epitopes associated with protective asymptomatic B- and T-cell immune responses, respectively. We demonstrated that unvaccinated asymptomatic patients with COVID-19 recognized these conserved B- and T-cell epitopes. Using the mRNA-LNP-based antigen delivery system, we developed a multi-epitope vaccine that incorporates the conserved B-cell epitopes, CD4+ T-cell epitopes, and CD8+ T-cell epitopes. To assess the efficacy of this "asymptomatic" multi-epitope vaccine, we used the HLA-A*02:01/HLA-DRB1* 01:01-hACE-2 triple transgenic mouse model. We demonstrated that this "asymptomatic" multi-epitope vaccine conferred robust protection against infection and disease caused by the SARS-CoV-2 Delta (B.1.617.2) and Omicron (XBB.1.5) variants as assessed by: (i) prevention of weight loss, (ii) reduction of virus replication, and (iii) lung pathology. This protection was associated with: (i) strong antibody responses; and (ii) high frequency of anti-viral IFN-γ-producing CD4+ and CD8+ T-cells. These findings illustrate the possibility of developing a pan-beta-coronavirus vaccine to induce broad-spectrum protective immunity against SARS-CoV-2 variants and sub-variants by targeting highly conserved "asymptomatic" B- and T-cell epitopes identified from both structural and non-structural viral proteins.

Epitopes, T-Lymphocyte↗
PubMed2026

Chimeric vaccine based on Iraqi HLA alleles against a predominant local Escherichia coli phylogroup.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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.

Animals↗
PubMed2026

Computational prediction of a multi-epitope Human Metapneumovirus vaccine candidate through integrated reverse vaccinology and pan-genomic approaches.

Human metapneumovirus (HMPV) is a primary cause of global respiratory infections yet no approved vaccine currently exists. This study computationally predicts a multi-epitope vaccine candidate using a diverse dataset of 65 HMPV sequences spanning five continents. Following the screening of lead proteins for antigenicity and virulence, fifteen highly conserved MHC-I, MHC-II and B-cell epitopes were prioritized. These were integrated with a putative L7/L12 adjuvant using optimized AAY, GPGPG, and KK linkers to design three constructs (HMPV_V1-V3). Structural validation identified HMPV-V2 as the lead candidate that exhibits a Z-score of-5.24 and 87.7% of residues in favored Ramachandran regions indicating excellent stereochemical quality and structural stability. In silico docking indicated a strong predicted binding affinity between HMPV-V2 and the TLR4 receptor (energy: -969.2). Immune simulations predicted a robust adaptive response characterized by high IgG1 titers, memory B-cell maturation, and a Th1-dominant cytokine profile. Furthermore, molecular dynamics simulations suggested exceptional structural integrity for HMPV-V2, maintaining a low RMSD of 8.213 and RMSF of 0.737 throughout the simulation. Optimized in silico cloning into the pET28a (+) vector indicated a high potential for protein expression in E. coli systems. While these findings provide a theoretically grounded blueprint for vaccine development, this study is entirely computational and lacks experimental validation. Further in vitro and in vivo testing is required to confirm the actual safety and immunogenicity of the proposed candidate.

Metapneumovirus↗
PubMed2026

Influence of Major Histocompatibility Complex (MHC) Diversity on Immune Modulation, Pathogenesis, and Control of Lumpy Skin Disease Virus.

INTRODUCTION: Lumpy Skin Disease Virus (LSDV), a member of the genus Capripoxvirus within the family Poxviridae, is an economically important transboundary viral pathogen affecting cattle and water buffalo. The disease causes severe production losses through decreased milk yield, infertility, hide damage, reduced growth performance, and occasional mortality. The rapid geographic spread of LSDV, together with its vectorborne transmission and emerging recombinant strains, has intensified the need for improved understanding of viral pathogenesis, host immune responses, and effective prevention strategies. In particular, the role of the bovine Major Histocompatibility Complex (BoLA/MHC) in regulating antiviral immunity, disease susceptibility, and vaccine responsiveness has gained increasing scientific attention. METHODS: This review summarises the published literature related to the epidemiology, transmission, structure, pathogenesis, diagnosis, prevention, and control of LSDV, with special emphasis on the immunological and molecular role of bovine MHC molecules. Relevant studies concerning BoLA-mediated antigen presentation, immunoinformaticsbased epitope prediction, vaccine development, antiviral drug repurposing, molecular docking, genomic surveillance, and diagnostic approaches, including PCR- and ELISAbased assays, were critically evaluated. Recent advances in computational biology, molecular virology, and host-pathogen interaction studies were also reviewed. RESULTS: The reviewed studies demonstrate that Lumpy Skin Disease Virus (LSDV) possesses a complex double-stranded DNA genome enabling immune modulation and efficient transmission through arthropod vectors such as mosquitoes, ticks, and biting flies. Disease progression involves systemic viral replication, vascular injury, dermal necrosis, and inflammatory skin lesions. Real-time PCR remains the most sensitive diagnostic method for early detection, while ELISA supports surveillance. Evidence highlights the central role of bovine Major Histocompatibility Complex (BoLA) molecules in antigen presentation and T-cell activation. Computational studies identified promising BoLA-binding epitopes and repurposed antiviral candidates, including ivermectin, theaflavin, canagliflozin, and tepotinib, for future therapeutic development. DISCUSSION: Current evidence indicates that effective LSDV control requires integration of molecular diagnostics, vector management, vaccination, and host immunogenetics. BoLAguided immunoinformatics provides promising opportunities for developing multi-epitope vaccines, although experimental validation remains essential. Similarly, repurposed antiviral candidates require comprehensive in vivo and pharmacological evaluation before clinical application. Future research should focus on elucidating viral immune-evasion mechanisms, validating predicted epitopes, and translating computational findings into practical vaccines and therapeutics for sustainable disease control. CONCLUSION: Lumpy Skin Disease continues to pose a major threat to global cattle health and livestock economies. Advances in molecular diagnostics, genomic surveillance, antiviral drug discovery, and BoLA-guided vaccine design provide promising opportunities for improved disease control. Understanding the interaction between LSDV and the bovine MHC system is essential for developing next-generation vaccines, immunotherapeutics, and precision disease-management strategies. Future research should prioritise experimental validation of predicted epitopes, large-scale vaccine trials, and mechanistic studies on host-virus immune interactions to establish effective and sustainable global control programs for LSDV.

BoLA↗
PubMed2026

A Multiepitope Intranasal Adenoviral Vaccine Induces Robust Mucosal Immunity and Protection against SARS‑CoV‑2.

BACKGROUND: Vaccination has been central to mitigating the COVID-19 pandemic; however, the continual emergence of SARS-CoV-2 variants of concern (VOCs) has reduced the effectiveness of current intramuscular vaccines that primarily target the Spike (S) protein. Although updated formulations are periodically introduced, there remains a critical need for next-generation vaccine platforms capable of inducing broad, variant-independent protection. Here we evaluate a heterologous intranasal (i.n.) prime-boost vaccination strategy using bovine adenoviral (BAd) and chimpanzee adenoviral (ChAd) vectors expressing the S1 subunit in combination with either full-length membrane (M) and nucleocapsid (N) proteins (Ad-S1 + N + M) or multiepitope constructs derived from M and N (Ad-S1 + Epi/N + Epi/M). The constructs were incorporated with the autophagy-inducing peptide C5 (AIP-C5) to enhance antigen-specific T-cell responses. RESULTS: In BALB/c mice, Ad-S1 + Epi/N + Epi/M vaccination induced robust S1-specific immunity while simultaneously inducing strong N- and M-specific humoral and cellular responses that were comparable to or greater than those induced by Ad-S1 + N + M. All S1-containing formulations generated high neutralizing antibody titers (~ 3.8 log₁₀) against Omicron B.1.1.529 and BA.2.86 variants, although titers against the ancestral Wuhan strain were approximately one log₁₀ lower. In K18-hACE2 mice, i.n. immunization with S1-expressing vectors provided near-complete protection against BA.2.86 challenge, with undetectable lung viral titers and viral genome copies. CONCLUSION: An i.n. multiepitope adenoviral vaccine incorporating conserved SARS-CoV-2 antigens induces robust mucosal, humoral, and cellular immune responses and confers significant protection following SARS-CoV-2 challenge.

Animals↗