Design of a multi-epitope vaccine against six Nocardia species based on reverse vaccinology combined with immunoinformatics

Abstract

BackgroundNocardia genus, a complex group of species classified to be aerobic actinomycete, can lead to severe concurrent infection as well as disseminated infection, typically in immunocompromised patients. With the expansion of the susceptible population, the incidence of Nocardia has been gradually growing, accompanied by increased resistance of the pathogen to existing therapeutics. However, there is no effective vaccine against this pathogen yet. In this study, a multi-epitope vaccine was designed against the Nocardia infection using reverse vaccinology combined with immunoinformatics approaches.MethodsFirst, the proteomes of 6 Nocardia subspecies Nocardia subspecies (Nocardia farcinica, Nocardia cyriacigeorgica, Nocardia abscessus, Nocardia otitidiscaviarum, Nocardia brasiliensis and Nocardia nova) were download NCBI (National Center for Biotechnology Information) database on May 1st, 2022 for the target proteins selection. The essential, virulent-associated or resistant-associated, surface-exposed, antigenic, non-toxic, and non-homologous with the human proteome proteins were selected for epitope identification. The shortlisted T-cell and B-cell epitopes were fused with appropriate adjuvants and linkers to construct vaccines. The physicochemical properties of the designed vaccine were predicted using multiple online servers. The Molecular docking and molecular dynamics (MD) simulation were performed to understand the binding pattern and binding stability between the vaccine candidate and Toll-like receptors (TLRs). The immunogenicity of the designed vaccines was evaluated via immune simulation.Results3 proteins that are essential, virulent-associated or resistant-associated, surface-exposed, antigenic, non-toxic, and non-homologous with the human proteome were selected from 218 complete proteome sequences of the 6 Nocardia subspecies epitope identification. After screening, only 4 cytotoxic T lymphocyte (CTL) epitopes, 6 helper T lymphocyte (HTL) epitopes, and 8 B cell epitopes that were antigenic, non-allergenic, and non-toxic were included in the final vaccine construct. The results of molecular docking and MD simulation showed that the vaccine candidate has a strong affinity for TLR2 and TLR4 of the host and the vaccine-TLR complexes were dynamically stable in the natural environment. The results of the immune simulation indicated that the designed vaccine had the potential to induce strong protective immune responses in the host. The codon optimization and cloned analysis showed that the vaccine was available for mass production.ConclusionThe designed vaccine has the potential to stimulate long-lasting immunity in the host, but further studies are required to validate its safety and efficacy.

Discovery of Novel Diagnostic Biomarkers for Common Pathogenic Nocardia through Pan- genome and Comparative Genome Analysis, with Preliminary Validation

“…The results of this study indicate that the speci c core genes identi ed in this research have the potential to signi cantly enhance the precise identi cation of clinical Nocardia infections, consequently leading to improved patient outcomes.Firstly, we analyzed the genomic characterization of several common pathogenic Nocardia species, revealing interesting insights into their genetic diversity and relevance to other bacterial species. The larger genome size and number of genes in Nocardia compared to NTM, MTB, Gordonia and Tsukamurella suggests a higher level of genetic complexity and adaptability in Nocardia spp., consistent with previous descriptions [4,34,35]. Phylogenetic analyses supported these ndings, with N. farcinica and N. cyriacigeorgica forming a densely packed cluster and N. brasiliensis acting as a distinct branch, suggesting distinct evolutionary relationships between these common pathogenic species.…”

“…Nocardia is known to cause nocardiosis, a group of serious opportunistic infections that primarily cause lung and skin infections affecting individuals of varying immune status [2,3]. In recent years, there has been a notable increase in the number of reported Nocardia infections in both immunocompromised and immunocompetent populations [4,5], and lack of timely and accurate treatment can lead to worsening clinical symptoms and high mortality [6][7][8]. Therefore, accurate and timely diagnosis of Nocardia infections is critical to guide appropriate clinical management and improve patient outcomes [9][10][11].…”

The Screening of the Protective Antigens of Aeromonas hydrophila Using the Reverse Vaccinology Approach: Potential Candidates for Subunit Vaccine Development

“…Zhu et al selected three antigens from the proteome of six Nocardia subspecies for epitope identification based on reverse vaccinology. The shortlisted T and B cell epitopes were fused with appropriate adjuvants and adaptors to construct the vaccine, and the immune simulation results suggest that the vaccine has the potential to induce a strong protective immune response in the host [ 60 ]. Li et al analyzed the epitopes of Brucella outer membrane protein 10, outer membrane protein 25, outer membrane protein 31, and BtpB based on reverse vaccinology, and constructed a final MEV containing 806 amino acids by connecting adaptors and adjuvants, and found MEV to be highly immunogenic in animal experiments [ 61 ].…”

Unleashing the Immune Arsenal: Development of Broad-spectrum Multiepitope Bluetongue Vaccine Targeting Conserved T Cell Epitopes of Structural Proteins

“…Subsequent equilibration steps involved NVT ensemble at 300K and NPT ensemble with the Parinello-Rahman barostat coupling ensembles (Parrinello 1981). Following equilibration, a 100ns MDS was performed for all four docked complexes, a standard duration in MD simulations for multi-epitope vaccine development (Sirohi, Gupta et al 2022, Hou, Wu et al 2023, Jyotisha, Qureshi et al 2023, Zhu, Tan et al 2023). Trajectories were analyzed post-simulation, and plots were generated using various GROMACS package modules.…”