Pangenome-guided immunoinformatics design and in silico characterization of a multi-epitope vaccine candidate against Acinetobacter baumannii with nanoparticle assembly potential.
This in silico characterized vaccine construct represents a promising candidate requiring experimental validation against A. baumannii infections, and computationally design and in silico characterize a self-assembling nanoparticle vaccine with dual adjuvants.
Abstract
Acinetobacter baumannii is a critical multidrug-resistant pathogen causing severe healthcare infections with high mortality, yet no licensed vaccine exists. This study aims to identify universally conserved surface antigens through pangenome analysis, predict immunogenic epitopes using integrated machine learning, and computationally design and in silico characterize a self-assembling nanoparticle vaccine with dual adjuvants. A computational framework integrating pangenome analysis of 712 complete genomes, epitope prediction, and structural vaccinology was employed to design a multi-epitope nanoparticle vaccine candidate for experimental evaluation. Pangenome analysis identified 3894 core genes with 42 outer membrane proteins, prioritizing OmpA, BamA, and OmpW as antigen targets. Protein language models predicted conformational B-cell epitopes, while NetMHCpan-4.2 predicted T-cell epitopes across 125 HLA alleles. The final construct (AB-VAX-01, 289 amino acids) incorporates 15 epitopes fused with dual adjuvants (RS09 TLR4 and cGAMP STING agonists) and a foldon domain for nanoparticle assembly. Microsecond molecular dynamics simulations with replicates demonstrated stability with TLR4 and STING. Conservation analysis across all 712 genomes showed 96.2-100% epitope identity. Immune simulations predicted Th1-biased responses with 94.2% global population coverage. In silico cloning confirmed favorable codon adaptation parameters. This in silico characterized vaccine construct represents a promising candidate requiring experimental validation against A. baumannii infections.
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.
E. K. Oladipo, James Akinwumi Ogunniran, Oluwaseyi Samuel Akinpelu et al.· Discover Immunity· 0 citations
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.
Safoura Moradkasani, N. Noori Goodarzi, M. Beig et al.· Journal of Genetic Engineeri...· 1 citation
The proposed multi-epitope vaccine shows promising immunological and structural properties, supporting its potential against S. typhimurium, pending experimental validation.
Mohammed Naveez Valathoor, A. P. Rajan· Scientific Reports· 0 citations
This study presents a structurally optimized and validated multiepitope vaccine candidate against the emerging Batai orthobunyavirus, identifying a promising vaccine candidate for further investigation; however, its immunogenicity, safety, and protective efficacy before further vaccine development can be considered.
M. A. Alwaili, N. Al‐Hoshani, Huda A Alqahtani et al.· Pharmaceuticals· 0 citations
The 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.
O. P. Emmanuel, M. N. Y. Sandrine, Bilanda Danielle Claude et al.· Scientific Reports· 0 citations
