Identification of novel putative immunogenic targets and construction of a multi-epitope vaccine against multidrug-resistant Corynebacterium jeikeium using reverse vaccinology approach. (March 2022)

• Record Type: Journal Article
• Authors: Shahbazi, Shahla; Sabzi, Samira; Noori Goodarzi, Narjes; Fereshteh, Sepideh; Bolourchi, Negin; Mirzaie, Bahman; Badmasti, Farzad
• Is Part Of: Microbial pathogenesis. Volume 164(2022)
• Publication Date: 2022-03
• Subjects: Corynebacterium jeikeium -- Nosocomial pathogen -- Immunogenic targets -- Multi-epitope vaccine; Pathogenic microorganisms -- Periodicals; Pathology, Molecular -- Periodicals; Communicable Diseases -- microbiology -- Periodicals; Communicable Diseases -- parasitology -- Periodicals; Micro-organismes pathogènes -- Périodiques; Pathologie moléculaire -- Périodiques; Electronic journals; 616.9041
• DOI: 10.1016/j.micpath.2022.105425
• Languages: English
• ISSNs: 0882-4010

Abstract

Abstract: The emergence of multidrug-resistant Corynebacterium jeikeium has limited treatment options and resulted in the inability to treat C. jeikeium infections, especially in immunocompromised patients. To our knowledge, no studies have been conducted to evaluate C. jeikeium antigens for vaccine development. Given the lack of effective treatments against C. jeikeium, this study aimed to identify potential immunogenic targets against C. jeikeium as a nosocomial pathogen using a reverse vaccinology approach. To achieve this goal, we performed several immuninformatics analyses, including antigenicity, allergenicity, PSI-BLAST to the human proteome, physiochemical properties, B-cell and T-cell epitopes, molecular docking, and immunosimulation. In addition, quartile scoring and prevalence assessment were used to select the most abundant immunogenic targets in different C. jeikeium strains. Finally, protein-protein interactions were performed and the multi-epitope vaccine was developed. Five putative immunogenic targets were presented as short-listed proteins in this study, including three enzymatic proteins (WP_011273969.1, WP_041626322.1, and WP_005292204.1), one protein with DUF3235 domain (WP_011273103.1), and one hypothetical protein (WP_005293648.1). Four linear B-cell epitopes of putative immunogenic targets, including WP_011273103.1 (LNSKPTPRNAAAKPKAK), WP_011273969.1 (GEGAQGSAAPADAQATANE), WP_005292204.1 (ASVSAAQKADGIAP), and WP_041626322.1 (YSKKVAEEMGVG) were selected and inserted into the mutant TbpB C-lobe protein. This platform can effectively present multiple epitopes to the immune system. However, experimental in vitro and in vivo analysis is required to confirm the safety, immunoreactivity, and efficacy of these putative immunogenic targets. Highlights: Five immunogenic targets as shortlisted proteins were identified against Corynebacterium jeikeium . WP_041626322.1, WP_005292204.1, and WP_005293648.1 showed the strongest molecular docking and immune simulation properties. A multi-epitope vaccine was designed by the mutant TbpB C-lobe of N. meningitidis M982 and four linear B-cell epitopes.