{"title":"多层次系统生物学分析确定了M72/AS01E疫苗对结核病保护的关键免疫反应概况和潜在相关因素。","authors":"Oluwaseun Oluwatosin Taofeek, Solomon Osarumwense Alile, Elcanah Mauta Evans, Louis Odinakaose Ezediuno, Ifeoluwa Adeniyi George, Olawale Moses Oyewole, Peter Ngo'la Owiti, Lateef Adegboyega Sulaimon","doi":"10.7774/cevr.2025.14.e21","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Tuberculosis (TB) claims around 1.5 million lives annually. The M72/AS01E vaccine candidate is an innovative effort demonstrating a 50% reduction in the incidence of active TB in adults. However, optimization and effective immunization strategies against TB depends heavily on precise identification of specific molecular signatures active in vaccine protection.</p><p><strong>Materials and methods: </strong>In this study, we employed weighted gene co-expression network analysis, machine learning, and network biology to investigate the gene expression patterns of peripheral blood mononuclear cells, identifying transcriptomic markers of vaccine protection.</p><p><strong>Results: </strong>Our comprehensive exploration of publicly available gene expression dataset comprising samples from subjects vaccinated twice with 10 μg of M72/AS01E vaccine one day post-second dose (D31) and one week post-second dose (D37) in a phase IIA clinical trial revealed intense induction of multiple gene modules, indicative of acute/immediate immune response at D31 that subsided by D37. Thirty-one hub genes with significant elevation/correlation with immune protection were identified significantly mediating key events in immunity to TB. The more selective profile at D37 involved additional adaptive immunity pathways including T helper (Th) 1/Th2/Th17 differentiation, T cell receptor and cytokine signaling. The functional relevance of these biomarkers in predicting vaccine response was further analyzed using the Random Forest classifier demonstrating high accuracy in distinguishing between vaccinated and non-vaccinated samples. Additionally, the study pinpointed a miRNAs-transcription factors (TF)-target regulatory network excavating key TF, miRNA, mRNAs mediating vaccine protection.</p><p><strong>Conclusion: </strong>Our results provided new insights into M72/AS01E immunity, warranting further study to optimize and guide future TB vaccine development.</p>","PeriodicalId":51768,"journal":{"name":"Clinical and Experimental Vaccine Research","volume":"14 3","pages":"210-228"},"PeriodicalIF":1.3000,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12303709/pdf/","citationCount":"0","resultStr":"{\"title\":\"Multilevel systems biology analysis identifies key immune response profiles and potential correlates of protection for M72/AS01E vaccine against tuberculosis.\",\"authors\":\"Oluwaseun Oluwatosin Taofeek, Solomon Osarumwense Alile, Elcanah Mauta Evans, Louis Odinakaose Ezediuno, Ifeoluwa Adeniyi George, Olawale Moses Oyewole, Peter Ngo'la Owiti, Lateef Adegboyega Sulaimon\",\"doi\":\"10.7774/cevr.2025.14.e21\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>Tuberculosis (TB) claims around 1.5 million lives annually. The M72/AS01E vaccine candidate is an innovative effort demonstrating a 50% reduction in the incidence of active TB in adults. However, optimization and effective immunization strategies against TB depends heavily on precise identification of specific molecular signatures active in vaccine protection.</p><p><strong>Materials and methods: </strong>In this study, we employed weighted gene co-expression network analysis, machine learning, and network biology to investigate the gene expression patterns of peripheral blood mononuclear cells, identifying transcriptomic markers of vaccine protection.</p><p><strong>Results: </strong>Our comprehensive exploration of publicly available gene expression dataset comprising samples from subjects vaccinated twice with 10 μg of M72/AS01E vaccine one day post-second dose (D31) and one week post-second dose (D37) in a phase IIA clinical trial revealed intense induction of multiple gene modules, indicative of acute/immediate immune response at D31 that subsided by D37. Thirty-one hub genes with significant elevation/correlation with immune protection were identified significantly mediating key events in immunity to TB. The more selective profile at D37 involved additional adaptive immunity pathways including T helper (Th) 1/Th2/Th17 differentiation, T cell receptor and cytokine signaling. The functional relevance of these biomarkers in predicting vaccine response was further analyzed using the Random Forest classifier demonstrating high accuracy in distinguishing between vaccinated and non-vaccinated samples. Additionally, the study pinpointed a miRNAs-transcription factors (TF)-target regulatory network excavating key TF, miRNA, mRNAs mediating vaccine protection.</p><p><strong>Conclusion: </strong>Our results provided new insights into M72/AS01E immunity, warranting further study to optimize and guide future TB vaccine development.</p>\",\"PeriodicalId\":51768,\"journal\":{\"name\":\"Clinical and Experimental Vaccine Research\",\"volume\":\"14 3\",\"pages\":\"210-228\"},\"PeriodicalIF\":1.3000,\"publicationDate\":\"2025-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12303709/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical and Experimental Vaccine Research\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.7774/cevr.2025.14.e21\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/3/31 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q4\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical and Experimental Vaccine Research","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.7774/cevr.2025.14.e21","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/3/31 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Multilevel systems biology analysis identifies key immune response profiles and potential correlates of protection for M72/AS01E vaccine against tuberculosis.
Purpose: Tuberculosis (TB) claims around 1.5 million lives annually. The M72/AS01E vaccine candidate is an innovative effort demonstrating a 50% reduction in the incidence of active TB in adults. However, optimization and effective immunization strategies against TB depends heavily on precise identification of specific molecular signatures active in vaccine protection.
Materials and methods: In this study, we employed weighted gene co-expression network analysis, machine learning, and network biology to investigate the gene expression patterns of peripheral blood mononuclear cells, identifying transcriptomic markers of vaccine protection.
Results: Our comprehensive exploration of publicly available gene expression dataset comprising samples from subjects vaccinated twice with 10 μg of M72/AS01E vaccine one day post-second dose (D31) and one week post-second dose (D37) in a phase IIA clinical trial revealed intense induction of multiple gene modules, indicative of acute/immediate immune response at D31 that subsided by D37. Thirty-one hub genes with significant elevation/correlation with immune protection were identified significantly mediating key events in immunity to TB. The more selective profile at D37 involved additional adaptive immunity pathways including T helper (Th) 1/Th2/Th17 differentiation, T cell receptor and cytokine signaling. The functional relevance of these biomarkers in predicting vaccine response was further analyzed using the Random Forest classifier demonstrating high accuracy in distinguishing between vaccinated and non-vaccinated samples. Additionally, the study pinpointed a miRNAs-transcription factors (TF)-target regulatory network excavating key TF, miRNA, mRNAs mediating vaccine protection.
Conclusion: Our results provided new insights into M72/AS01E immunity, warranting further study to optimize and guide future TB vaccine development.
期刊介绍：
Clin Exp Vaccine Res, the official English journal of the Korean Vaccine Society, is an international, peer reviewed, and open-access journal. It covers all areas related to vaccines and vaccination. Clin Exp Vaccine Res publishes editorials, review articles, special articles, original articles, case reports, brief communications, and correspondences covering a wide range of clinical and experimental subjects including vaccines and vaccination for human and animals against infectious diseases caused by viruses, bacteria, parasites and tumor. The scope of the journal is to disseminate information that may contribute to elaborate vaccine development and vaccination strategies targeting infectious diseases and tumors in human and animals. Relevant topics range from experimental approaches to (pre)clinical trials for the vaccine research based on, but not limited to, basic laboratory, translational, and (pre)clinical investigations, epidemiology of infectious diseases and progression of all aspects in the health related issues. It is published printed and open accessed online issues (https://ecevr.org) two times per year in 31 January and 31 July. Clin Exp Vaccine Res is linked to many international databases and is made freely available to institutions and individuals worldwide
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
