Significant transcriptome and cytokine changes in hepatitis B vaccine non-responders revealed by genome-wide comparative analysis

Individuals fail to elicit protective antibody after hepatitis B vaccination remain at risk for hepatitis B virus infection. Analysis of the transcriptome of peripheral blood mononuclear cells (PBMCs) is essential to elucidate the characteristics of gene expression in non-responders. In this study,...

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Main Authors: Shaohui Qiu, Peng He, Xin Fang, Haiqing Tong, Jingjing Lv, Jiaye Liu, Li Zhang, Xiangjun Zhai, Liying Wang, Zhongyu Hu, Yongli Yu
Format: Article
Language:English
Published: Taylor & Francis Group 2018-07-01
Series:Human Vaccines & Immunotherapeutics
Subjects:
Online Access:http://dx.doi.org/10.1080/21645515.2018.1450122
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author Shaohui Qiu
Peng He
Xin Fang
Haiqing Tong
Jingjing Lv
Jiaye Liu
Li Zhang
Xiangjun Zhai
Liying Wang
Zhongyu Hu
Yongli Yu
author_facet Shaohui Qiu
Peng He
Xin Fang
Haiqing Tong
Jingjing Lv
Jiaye Liu
Li Zhang
Xiangjun Zhai
Liying Wang
Zhongyu Hu
Yongli Yu
author_sort Shaohui Qiu
collection DOAJ
description Individuals fail to elicit protective antibody after hepatitis B vaccination remain at risk for hepatitis B virus infection. Analysis of the transcriptome of peripheral blood mononuclear cells (PBMCs) is essential to elucidate the characteristics of gene expression in non-responders. In this study, we enrolled seven responders who had received three injections and seven non-responders who had six injections of hepatitis B vaccine before. All the participants were then vaccinated with a three-dose boost regimen. Microarray analysis and Luminex assay were applied to examine mRNA expression and Th1/Th2/Th9/Th17/Th22/Treg cytokine and chemokine profiles in non-responders and responders. Differentially expressed genes in PBMCs of non-responders at 5 time points, i.e. pre-vaccination, 3rd, 7th, 28th day post the first dose vaccination and 7th day post the second dose vaccination indicated a dense network trend. Compared with responders, nine coding genes (BPI, DEFA1B, DEFA4, CEACAM8, MMP8, FOLR3, LTF, TCN1 and TKTL1) were significantly up-regulated in non-responders at all 5 time points, which could probably be the characteristic genes in hepatitis B vaccine non-responsiveness. Gene ontology analysis revealed that most of the DEGs were related with immune responses. Validation results of these 9 genes using quantitative real-time polymerase chain reaction were mostly consistent with the results of microarray. Cytokine analysis demonstrated that IL-27 and CXCL12 concentrations in responders were significantly higher than non-responders on the 3rd day after the first dose and 7th day after the second dose of vaccination, respectively. No significant difference was observed in other cytokine and chemokine signatures between the two groups. In conclusion, our results revealed characteristic transcriptome and cytokine changes in hepatitis B vaccine non-responders after boost immunization.
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spelling doaj.art-9203a40fb44a47a48e8754cdaaa983332023-09-22T08:17:55ZengTaylor & Francis GroupHuman Vaccines & Immunotherapeutics2164-55152164-554X2018-07-011471763177210.1080/21645515.2018.14501221450122Significant transcriptome and cytokine changes in hepatitis B vaccine non-responders revealed by genome-wide comparative analysisShaohui Qiu0Peng He1Xin Fang2Haiqing Tong3Jingjing Lv4Jiaye Liu5Li Zhang6Xiangjun Zhai7Liying Wang8Zhongyu Hu9Yongli Yu10College of Basic Medical Sciences, Jilin UniversityKey Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products, Division of Hepatitis Virus Vaccines, National Institutes for Food and Drug ControlKey Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products, Division of Hepatitis Virus Vaccines, National Institutes for Food and Drug ControlKey Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products, Division of Hepatitis Virus Vaccines, National Institutes for Food and Drug ControlShandong Provincial Center for Disease Control and PreventionShandong Provincial Center for Disease Control and PreventionShandong Provincial Center for Disease Control and PreventionJiangsu Provincial Center for Disease Control and PreventionCollege of Basic Medical Sciences, Jilin UniversityKey Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products, Division of Hepatitis Virus Vaccines, National Institutes for Food and Drug ControlCollege of Basic Medical Sciences, Jilin UniversityIndividuals fail to elicit protective antibody after hepatitis B vaccination remain at risk for hepatitis B virus infection. Analysis of the transcriptome of peripheral blood mononuclear cells (PBMCs) is essential to elucidate the characteristics of gene expression in non-responders. In this study, we enrolled seven responders who had received three injections and seven non-responders who had six injections of hepatitis B vaccine before. All the participants were then vaccinated with a three-dose boost regimen. Microarray analysis and Luminex assay were applied to examine mRNA expression and Th1/Th2/Th9/Th17/Th22/Treg cytokine and chemokine profiles in non-responders and responders. Differentially expressed genes in PBMCs of non-responders at 5 time points, i.e. pre-vaccination, 3rd, 7th, 28th day post the first dose vaccination and 7th day post the second dose vaccination indicated a dense network trend. Compared with responders, nine coding genes (BPI, DEFA1B, DEFA4, CEACAM8, MMP8, FOLR3, LTF, TCN1 and TKTL1) were significantly up-regulated in non-responders at all 5 time points, which could probably be the characteristic genes in hepatitis B vaccine non-responsiveness. Gene ontology analysis revealed that most of the DEGs were related with immune responses. Validation results of these 9 genes using quantitative real-time polymerase chain reaction were mostly consistent with the results of microarray. Cytokine analysis demonstrated that IL-27 and CXCL12 concentrations in responders were significantly higher than non-responders on the 3rd day after the first dose and 7th day after the second dose of vaccination, respectively. No significant difference was observed in other cytokine and chemokine signatures between the two groups. In conclusion, our results revealed characteristic transcriptome and cytokine changes in hepatitis B vaccine non-responders after boost immunization.http://dx.doi.org/10.1080/21645515.2018.1450122hepatitis bvaccinenon-respondermicroarraytranscriptomecytokine
spellingShingle Shaohui Qiu
Peng He
Xin Fang
Haiqing Tong
Jingjing Lv
Jiaye Liu
Li Zhang
Xiangjun Zhai
Liying Wang
Zhongyu Hu
Yongli Yu
Significant transcriptome and cytokine changes in hepatitis B vaccine non-responders revealed by genome-wide comparative analysis
Human Vaccines & Immunotherapeutics
hepatitis b
vaccine
non-responder
microarray
transcriptome
cytokine
title Significant transcriptome and cytokine changes in hepatitis B vaccine non-responders revealed by genome-wide comparative analysis
title_full Significant transcriptome and cytokine changes in hepatitis B vaccine non-responders revealed by genome-wide comparative analysis
title_fullStr Significant transcriptome and cytokine changes in hepatitis B vaccine non-responders revealed by genome-wide comparative analysis
title_full_unstemmed Significant transcriptome and cytokine changes in hepatitis B vaccine non-responders revealed by genome-wide comparative analysis
title_short Significant transcriptome and cytokine changes in hepatitis B vaccine non-responders revealed by genome-wide comparative analysis
title_sort significant transcriptome and cytokine changes in hepatitis b vaccine non responders revealed by genome wide comparative analysis
topic hepatitis b
vaccine
non-responder
microarray
transcriptome
cytokine
url http://dx.doi.org/10.1080/21645515.2018.1450122
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