Bioinformatics analysis, immunogenicity, and therapeutic efficacy evaluation of a novel multi-stage, multi-epitope DNA vaccine for tuberculosis

IF 4.8 2区医学 Q2 IMMUNOLOGY

International immunopharmacology Pub Date : 2025-03-13 DOI:10.1016/j.intimp.2025.114415

Jinzhong Guo , Zaixing Jia , Yourong Yang , Nan Wang , Yong Xue , Li Xiao , Fenghua Wang , Lan Wang , Xiaoou Wang , Yinping Liu , Jie Wang , Wenping Gong , Haimei Zhao , Yan Liang , Xueqiong Wu

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引用次数: 0

Abstract

Background

The global tuberculosis (TB) epidemic remains severe. We aimed to develop a therapeutic DNA vaccine as an adjunct to TB treatment to improve efficacy.

Methods

The W545 DNA vaccine was constructed using the M. tuberculosis (MTB) antigens Ag85A and Rv1419, integrated with epitopes from the Ag85B, Rv3407, and Rv2628. Bioinformatics tools were used to predict and analyze the physicochemical properties, structure modelling and molecular docking, epitopes (HTL, CTL, and B-cell), safety, population coverage, and simulated immunization of the W545 vaccine protein. Animal studies were then performed to evaluate the vaccine's immunogenicity by measuring Th1-type immune responses (IFN-γ, IL-2) and IgG antibody levels, as well as its therapeutic efficacy in reducing lung inflammation and pathological damage in a murine TB model.

Results

The vaccine protein is a 70 kDa hydrophilic protein with a half-life of 30 h, an instability index of 43.33, and strong affinity to Toll-like receptor (TLR) 2 and TLR4. It contains 397 helper T cell (HTL) epitopes, 248 cytotoxic T cell (CTL) epitopes, and 27 B cell epitopes, with broad population coverage (global: 99.7 %, Chinese: 97.6 %). The W545 vaccine significantly induced a Th1-type immune response, producing high levels of IFN-γ (5.38 pg/ml ± 0.89 pg/ml) and IgG antibodies (OD450: 0.13 ± 0.06). It also reduced the lung weight index, tissue lesions, and severity in the murine TB model.

Conclusion

The W545 DNA vaccine effectively induces a Th1-type immune response, alleviates pathological damage, and demonstrates potential as an immunotherapeutic agent. Bioinformatics analysis provides valuable guidance for vaccine design and optimization.

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来源期刊

International immunopharmacology 医学-免疫学

CiteScore

8.40

自引率

3.60%

发文量

935

审稿时长

53 days

期刊介绍： International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.