Design and development of a multi‐epitope vaccine for the prevention of latent tuberculosis infection

Author:

Jiang Fan12,Wang Lingling3,Wang Jie1,Cheng Peng1,Shen Jing3,Gong Wenping1ORCID

Affiliation:

1. Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment Senior Department of Tuberculosis The Eighth Medical Center of PLA General Hospital Beijing China

2. Section of Health No. 94804 Unit of the Chinese People's Liberation Army Shanghai China

3. Department of Endocrinology The Eighth Medical Center of PLA General Hospital Beijing China

Abstract

AbstractBackgroundLatent tuberculosis infection (LTBI) often progresses to active tuberculosis, necessitating the development of novel vaccine to prevent LTBI. In this study, we aimed to design a Mycobacterium tuberculosis (M. tuberculosis) vaccine that could elicit a potent immune response to prevent LTBI.MethodsWe used bioinformatics and immunoinformatics techniques to develop a multi‐epitope vaccine (MEV) called C624P. The vaccine contained six cytotoxic T lymphocytes (CTL), two helper T lymphocytes (HTL), and four B‐cell epitopes derived from six antigens associated with LTBI and the Mycobacterium tuberculosis region of difference. We added Toll‐like receptor (TLR) agonists and PADRE peptide to the MEV to enhance its immunogenicity. We then analyzed the C624P vaccine's physical and chemical properties, spatial structure, molecular docking with TLRs, and immunological features.ResultsThe C624P vaccine displayed good antigenicity and immunogenicity scores of 0.901398 and 3.65609, respectively. The vaccine structure was stable, with 42.82% α‐helix content, a Z‐value of −7.84, and a favored Ramachandran plot area of 85.84% after majorization. Molecular docking analysis showed that the C624P vaccine could bind tightly to TLR2 (−1011.0 kcal/mol) and TLR4 (−941.4 kcal/mol). Furthermore, the C624P vaccine effectively stimulated T and B lymphocytes, resulting in high levels of Th1 cytokines such as IFN‐γ and IL‐2.ConclusionsThe C624P vaccine represents a promising MEV for preventing LTBI. The vaccine's good antigenicity, immunogenicity, stability, and ability to activate immune responses suggest its effectiveness in preventing LTBI. Our study demonstrated the utility of bioinformatics and immunoinformatics techniques in designing safe and effective tuberculosis vaccines.

Funder

National Key Research and Development Program of China

Publisher

Wiley

Reference79 articles.

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2. WHO.Global tuberculosis report 2022. Avaliable from: https://www.who.int/teams/global‐tuberculosis‐programme/tb‐reports/global‐tuberculosis‐report‐2022. Accessed on 1 May 2023.

3. Differential Diagnosis of Latent Tuberculosis Infection and Active Tuberculosis: A Key to a Successful Tuberculosis Control Strategy

4. Diagnosis for Latent Tuberculosis Infection: New Alternatives

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