利用反向疫苗学方法鉴定沙门氏菌潜在候选疫苗

IF 4.5 3区 医学 Q1 MICROBIOLOGY
Jie Li , Jingxuan Qiu , Zhiqiang Huang , Tao Liu , Jing Pan , Qi Zhang , Qing Liu
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引用次数: 17

摘要

沙门氏菌是食源性病原体的主要原因,在世界范围内引起肠道和全身疾病。接种疫苗是预防沙门氏菌最有效的方法,但由于沙门氏菌的多种血清型,鉴定和设计有效的广谱疫苗仍然是一个巨大的挑战。反向疫苗学是结合人类免疫学、结构生物学、计算生物学和微生物基因组学发现和设计疫苗抗原的新工具。本研究采用反向疫苗学方法,通过计算沙门氏菌583种非冗余外膜和分泌蛋白的免疫原性评分,建立了一种筛选合适免疫原靶点的计算机方法。在100个鉴定得分最高的蛋白中,随机选取15个具有代表性的抗原。通过序列保守试验,4种蛋白(FliK、BcsZ、FhuA和FepA)仍然是潜在的候选疫苗,可用于体内免疫原性和免疫保护评价。这四种候选药物都能在小鼠体内触发免疫反应并刺激抗血清的产生。此外,排名靠前的蛋白包括FliK和BcsZ,在沙门氏菌的多血清型中提供了广泛的抗原覆盖。FliK和BcsZ免疫小鼠鼠伤寒沙门氏菌LT2攻毒模型的相对存活率(RPS)分别为52.74%和64.71%。总之,本研究构建了一个能够成功预筛选具有高免疫原性和保护性免疫的疫苗靶点的硅管道。我们表明,反向疫苗学允许筛选适当的广谱沙门氏菌疫苗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Reverse vaccinology approach for the identifications of potential vaccine candidates against Salmonella

Salmonella is a leading cause of foodborne pathogen which causes intestinal and systemic diseases across the world. Vaccination is the most effective protection against Salmonella, but the identification and design of an effective broad-spectrum vaccine is still a great challenge, because of the multi-serotypes of Salmonella. Reverse vaccinology is a new tool to discovery and design vaccine antigens combining human immunology, structural biology and computational biology with microbial genomics. In this study, reverse vaccinology, an in-silico approach was established to screen appropriate immunogen targets by calculating the immunogenicity score of 583 non-redundant outer membrane and secreted proteins of Salmonella. Herein among 100 proteins identified with top-ranked scores, 15 representative antigens were selected randomly. Applying the sequence conservation test, four proteins (FliK, BcsZ, FhuA and FepA) remained as potential vaccine candidates for in vivo evaluation of immunogenicity and immunoprotection. All four candidates were capable to trigger the immune response and stimulate the production of antiserum in mice. Furthermore, top-ranked proteins including FliK and BcsZ provided wide antigenic coverage among the multi-serotype of Salmonella. The S. Typhimurium LT2 challenge model used in mice immunized with FliK and BcsZ showed a high relative percentage survival (RPS) of 52.74 % and 64.71 % respectively. In conclusion, this study constructed an in-silico pipeline able to successfully pre-screen the vaccine targets characterized by high immunogenicity and protective immunity. We show that reverse vaccinology allowed screening of appropriate broad-spectrum vaccines for Salmonella.

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来源期刊
CiteScore
9.70
自引率
0.00%
发文量
18
审稿时长
45 days
期刊介绍: Pathogen genome sequencing projects have provided a wealth of data that need to be set in context to pathogenicity and the outcome of infections. In addition, the interplay between a pathogen and its host cell has become increasingly important to understand and interfere with diseases caused by microbial pathogens. IJMM meets these needs by focussing on genome and proteome analyses, studies dealing with the molecular mechanisms of pathogenicity and the evolution of pathogenic agents, the interactions between pathogens and host cells ("cellular microbiology"), and molecular epidemiology. To help the reader keeping up with the rapidly evolving new findings in the field of medical microbiology, IJMM publishes original articles, case studies and topical, state-of-the-art mini-reviews in a well balanced fashion. All articles are strictly peer-reviewed. Important topics are reinforced by 2 special issues per year dedicated to a particular theme. Finally, at irregular intervals, current opinions on recent or future developments in medical microbiology are presented in an editorial section.
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