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

Frontiers in Immunology

Immunology

Fei Zhu¹  Hang Yang¹  Shiyang Ma¹  Wenzhong Peng¹  Yanhui Cui¹  Peipei Zhang¹  Mingjun Rao¹  Pinhua Pan¹  Jie Chen¹  Haicheng Wen²  Chunhui Li³  Caixia Tan³ 

[1] Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, Hunan, China;Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China;Clinical Research Center for Respiratory Diseases in Hunan Province, Changsha, Hunan, China;Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha, Hunan, China;National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China;National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China;National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China;Department of Infection Control Center of Xiangya Hospital, Central South University, Changsha, Hunan, China;

关键词: Nocardia;    immunoinformatics;    reverse vaccinology (RV);    multi-epitope vaccine;    molecular docking;    molecular dynamics (MD) simulation;   

DOI  :  10.3389/fimmu.2023.1100188

 received in 2022-11-16, accepted in 2023-01-13,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

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Copyright © 2023 Zhu, Tan, Li, Ma, Wen, Yang, Rao, Zhang, Peng, Cui, Chen and Pan