Pangenome-guided immunoinformatics design and in silico characterization of a multi-epitope vaccine candidate against Acinetobacter baumannii with nanoparticle assembly potential.

Harnessing reverse vaccinology for the design and validation of mRNA vaccine targeting the glycoprotein of human metapneumovirus (HMPV)

Human metapneumovirus (HMPV) is a major cause of respiratory illness among vulnerable populations worldwide, yet no licensed vaccine or specific antiviral therapy is currently available. This study aimed to design novel multi-epitope mRNA vaccine candidates against HMPV using an immunoinformatics-based approach. Globally representative HMPV glycoprotein sequences were analyzed to predict cytotoxic T-lymphocyte (CTL), helper T-lymphocyte (HTL), and linear B-cell (LBL) epitopes. Selected epitopes were assembled into two multi-epitope mRNA vaccine constructs. The constructs were further evaluated for antigenicity, allergenicity, toxicity, and physicochemical properties using in silico tools. Structural stability and immune receptor interactions were assessed through molecular modeling and molecular docking analyses against Toll-like receptors 2 and 4 (TLR2 and TLR4). Both vaccine constructs demonstrated high antigenicity, while remaining non-toxic and non-allergenic, with favorable physicochemical characteristics. Structural analyses indicated stable conformations of the vaccine models. Molecular docking studies revealed strong binding affinities with TLR2 and TLR4, suggesting their ability to effectively stimulate innate and adaptive immune responses. The two proposed multi-epitope mRNA vaccine constructs showed promising immunogenic, safety, and structural properties in silico, highlighting their potential as candidate vaccines against HMPV. These findings provide a strong foundation for further experimental validation and future vaccine development.

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.

Immunoinformatics-based design and in silico evaluation of a PstS-derived multi-epitope vaccine candidate against Salmonella typhimurium

The proposed multi-epitope vaccine shows promising immunological and structural properties, supporting its potential against S. typhimurium, pending experimental validation.

Structure-Guided Immunoinformatics for the Rational Design of a Multi-Epitope Vaccine Against Batai Orthobunyavirus

Background/Objectives: Batai orthobunyavirus (BATV) is an emerging mosquito-borne zoonotic pathogen for which no licensed vaccine is currently available. The viral envelope glycoprotein plays an important role in viral attachment and host immune recognition, making it a potential target for rational vaccine design. Methods: In this study, an immunoinformatics-based framework was used to design and evaluate a multi-epitope vaccine candidate targeting the BATV envelope glycoprotein. Selected B-cell, cytotoxic T-lymphocyte (CTL), and helper T-lymphocyte (HTL) epitopes were assembled using appropriate linkers and a human β-defensin adjuvant. Population coverage and in silico immune simulations were conducted to evaluate the potential breadth and magnitude of immune response. Results: The final vaccine construct demonstrated favorable physicochemical characteristics, high predicted antigenicity (0.7959), and non-allergenic properties while maintaining favorable predicted structural characteristics and broad predicted population coverage (99.92%). Structural docking revealed a stable interaction between the vaccine construct and human TLR4, with a weighted docking score of −1194.8, suggesting favorable molecular recognition and receptor engagement. Normal Mode Analysis further supported the structural stability and conformational integrity of the vaccine receptor complex. Immune simulation predicted robust primary and secondary immune responses characterized by elevated IgM and IgG antibody production, sustained memory cell formation, and strong IFN-γ and IL-2 responses, indicating the potential to elicit balanced humoral and cellular immunity. Conclusions: This study presents a structurally optimized and validated multiepitope vaccine candidate against the emerging Batai orthobunyavirus. These computational findings identified a promising vaccine candidate for further investigation; however, its immunogenicity, safety, and protective efficacy before further vaccine development can be considered.

Integrative immunoinformatics and structural modeling for the rational design of a multi-epitope vaccine candidate against human cytomegalovirus

Human cytomegalovirus (CMV) is a globally widespread pathogen associated with significant morbidity in immunocompromised individuals. Despite its clinical importance, no licensed vaccine is currently available. This study aimed to design a rational multi-epitope vaccine candidate targeting CMV using an integrative approach combining immunoinformatics and structural biology. Viral proteins were screened to identify epitopes with high affinity for B cells, cytotoxic T cells (CTLs), and helper T cells (HTLs) using the Immune Epitope Database (IEDB). Selected epitopes were filtered according to their antigenicity and toxicity and then assembled into a chimeric construct incorporating an immunostimulatory adjuvant. The designed vaccine was evaluated for its physicochemical properties, validated by Ramchandran and ERRAT analyses. Molecular modeling demonstrated strong and stable interactions with key innate immunity receptors, including TLR7 and TLR9, interactions confirmed by molecular dynamics simulations. In silico immune simulation predicted a robust and durable immune response, characterized by high levels of IgM and IgG, as well as significant activation of CD4 + and CD8 + lymphocytes and innate immunity components. These results highlight the potential of the proposed multi-epitope construct as a promising vaccine candidate against HCMV. However, experimental validation is essential to confirm its immunogenicity, safety, and translational applicability.

Immunoinformatics-guided design of a conserved multi-epitope vaccine candidate against pathogenic human coronaviruses.