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<p><i>Nocardia farcinica</i> is a rare but clinically significant pathogen causing nocardiosis, a severe opportunistic infection. Although isolates are generally susceptible to antibiotics such as amikacin, imipenem, ciprofloxacin, and trimethoprim-sulfamethoxazole, the recent emergence of resistant strains highlights the urgent need for novel therapeutic strategies. This study employed subtractive proteomics and reverse vaccinology methods to identify potential vaccine targets against <i>N. farcinica</i>. The reference proteome comprising 5934 proteins was analyzed, and host non-homologous proteins were identified after comparison with the human and gut microbiome proteomes. Subsequent analyses of virulence, antibiotic resistance, and subcellular localization led to the selection of potential drug and vaccine candidates. Among these, one protein (WP_011210770.1) met all physicochemical, antigenicity, and allergenicity criteria. The epitopes were predicted with T-cell epitopes showing 99.95% coverage of MHC-binding alleles. The multi-epitope vaccine construct was designed by incorporating selected specific B- and T-cell epitopes, adjuvants, linkers, and a PADRE sequence to enhance immunogenicity. The construct was evaluated for antigenicity, allergenicity, toxicity, and solubility, confirming its safety and immunogenic potential. Molecular docking, NMA evaluation, molecular dynamics simulations, principal component analysis, MM-GBSA, and dynamic cross-correlation analyses demonstrated stable interactions with the human TLR4 receptor. Immune simulations predicted that the vaccine may induce strong and sustained immune response, while codon optimization and in-silico cloning validated its expression feasibility in a bacterial host. In conclusion, this study predicted promising vaccine targets and proposed a chimeric vaccine candidate with strong predicted immunogenicity, warranting additional in-vitro and in-vivo validation to enhance therapeutic development against nocardiosis.</p>

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Computer-assisted design of a novel peptide vaccine against multidrug-resistant Nocardia farcinica

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月26日

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  • Hamna Bashir,
  • Asifa Sarfraz,
  • Muhammad Shehroz,
  • Fizza Arshad,
  • Umar Nishan,
  • Abid Ali,
  • Khaled Fahmi Fawy,
  • Mohibullah Shah

摘要

Nocardia farcinica is a rare but clinically significant pathogen causing nocardiosis, a severe opportunistic infection. Although isolates are generally susceptible to antibiotics such as amikacin, imipenem, ciprofloxacin, and trimethoprim-sulfamethoxazole, the recent emergence of resistant strains highlights the urgent need for novel therapeutic strategies. This study employed subtractive proteomics and reverse vaccinology methods to identify potential vaccine targets against N. farcinica. The reference proteome comprising 5934 proteins was analyzed, and host non-homologous proteins were identified after comparison with the human and gut microbiome proteomes. Subsequent analyses of virulence, antibiotic resistance, and subcellular localization led to the selection of potential drug and vaccine candidates. Among these, one protein (WP_011210770.1) met all physicochemical, antigenicity, and allergenicity criteria. The epitopes were predicted with T-cell epitopes showing 99.95% coverage of MHC-binding alleles. The multi-epitope vaccine construct was designed by incorporating selected specific B- and T-cell epitopes, adjuvants, linkers, and a PADRE sequence to enhance immunogenicity. The construct was evaluated for antigenicity, allergenicity, toxicity, and solubility, confirming its safety and immunogenic potential. Molecular docking, NMA evaluation, molecular dynamics simulations, principal component analysis, MM-GBSA, and dynamic cross-correlation analyses demonstrated stable interactions with the human TLR4 receptor. Immune simulations predicted that the vaccine may induce strong and sustained immune response, while codon optimization and in-silico cloning validated its expression feasibility in a bacterial host. In conclusion, this study predicted promising vaccine targets and proposed a chimeric vaccine candidate with strong predicted immunogenicity, warranting additional in-vitro and in-vivo validation to enhance therapeutic development against nocardiosis.