A unique B cell epitope-based particulate vaccine shows effective suppression of hepatitis B surface antigen in mice
ObjectiveThis study aimed to develop a novel therapeutic vaccine based on a unique B cell epitope and investigate its therapeutic potential against chronic hepatitis B (CHB) in animal models.MethodsA series of peptides and carrier proteins were evaluated in HBV-tolerant mice to obtain an optimised t...
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| Veröffentlicht in: | Gut 2020-02, Vol.69 (2), p.343-354 |
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| creator | Zhang, Tian-Ying Guo, Xue-Ran Wu, Yang-Tao Kang, Xiao-Zhen Zheng, Qing-Bing Qi, Ruo-Yao Chen, Bin-Bing Lan, Ying Wei, Min Wang, Shao-Juan Xiong, Hua-Long Cao, Jia-Li Zhang, Bao-Hui Qiao, Xiao-Yang Huang, Xiao-Fen Wang, Ying-Bin Fang, Mu-Jin Zhang, Ya-Li Cheng, Tong Chen, Yi-Xin Zhao, Qin-Jian Li, Shao-Wei Ge, Sheng-Xiang Chen, Pei-Jer Zhang, Jun Yuan, Quan Xia, Ning-shao |
| description | ObjectiveThis study aimed to develop a novel therapeutic vaccine based on a unique B cell epitope and investigate its therapeutic potential against chronic hepatitis B (CHB) in animal models.MethodsA series of peptides and carrier proteins were evaluated in HBV-tolerant mice to obtain an optimised therapeutic molecule. The immunogenicity, therapeutic efficacy and mechanism of the candidate were investigated systematically.ResultsAmong the HBsAg-aa119-125-containing peptides evaluated in this study, HBsAg-aa113-135 (SEQ13) exhibited the most striking therapeutic effects. A novel immunoenhanced virus-like particle carrier (CR-T3) derived from the roundleaf bat HBV core antigen (RBHBcAg) was created and used to display SEQ13, forming candidate molecule CR-T3-SEQ13. Multiple copies of SEQ13 displayed on the surface of this particulate antigen promote the induction of a potent anti-HBs antibody response in mice, rabbits and cynomolgus monkeys. Sera and purified polyclonal IgG from the immunised animals neutralised HBV infection in vitro and mediated efficient HBV/hepatitis B virus surface antigen (HBsAg) clearance in the mice. CR-T3-SEQ13-based vaccination induced long-term suppression of HBsAg and HBV DNA in HBV transgenic mice and eradicated the virus completely in hydrodynamic-based HBV carrier mice. The suppressive effects on HBsAg were strongly correlated with the anti-HBs level after vaccination, suggesting that the main mechanism of CR-T3-SEQ13 vaccination therapy was the induction of a SEQ13-specific antibody response that mediated HBV/HBsAg clearance.ConclusionsThe novel particulate protein CR-T3-SEQ13 suppressed HBsAg effectively through induction of a humoural immune response in HBV-tolerant mice. This B cell epitope-based therapeutic vaccine may provide a novel immunotherapeutic agent against chronic HBV infection in humans. |
| doi_str_mv | 10.1136/gutjnl-2018-317725 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6984059</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2348251578</sourcerecordid><originalsourceid>FETCH-LOGICAL-b507t-f2970743ca06a14f9258421c23a681a7d84506247e2a40cc8209be262668c61d3</originalsourceid><addsrcrecordid>eNqNkUuLFDEUhYMoTjv6B1xIwI2bGpNUKo-NMA6-YMCNrkMqfas7TVVSJqke_PemqbF9LMRVuOQ7h3vuQeg5JVeUtuL1bimHMDaMUNW0VErWPUAbykWdmFIP0YYQKptOcn2BnuR8IIQopeljdNESzYTo2g0q13gJ_tsC-C12MI4YZl_iDE1vM2zxbFPxbhltAXy0zvkAOO_jXcYwDOCKP9Z5mecEOfsYcBzwHmZbfPG5OuYlDdYBtqH4HQTsA568g6fo0WDHDM_u30v09f27Lzcfm9vPHz7dXN82fUdkaQamJZG8dZYIS_mgWac4o461Vihq5VbxjgjGJTDLiXOKEd0DEzWacoJu20v0ZvWdl36CrYNQkh3NnPxk03cTrTd__gS_N7t4NEIrTjpdDV7dG6RYb5SLmXw-nckGiEs2jBEiFWGaVvTlX-ghLinUeIa1XLGOdlJViq2USzHnBMN5GUrMqVSzlmpOpZq11Cp68XuMs-RnixVoVqCfDv9nePWLP6_5D8EPyAq8sQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2348251578</pqid></control><display><type>article</type><title>A unique B cell epitope-based particulate vaccine shows effective suppression of hepatitis B surface antigen in mice</title><source>MEDLINE</source><source>PubMed Central</source><creator>Zhang, Tian-Ying ; Guo, Xue-Ran ; Wu, Yang-Tao ; Kang, Xiao-Zhen ; Zheng, Qing-Bing ; Qi, Ruo-Yao ; Chen, Bin-Bing ; Lan, Ying ; Wei, Min ; Wang, Shao-Juan ; Xiong, Hua-Long ; Cao, Jia-Li ; Zhang, Bao-Hui ; Qiao, Xiao-Yang ; Huang, Xiao-Fen ; Wang, Ying-Bin ; Fang, Mu-Jin ; Zhang, Ya-Li ; Cheng, Tong ; Chen, Yi-Xin ; Zhao, Qin-Jian ; Li, Shao-Wei ; Ge, Sheng-Xiang ; Chen, Pei-Jer ; Zhang, Jun ; Yuan, Quan ; Xia, Ning-shao</creator><creatorcontrib>Zhang, Tian-Ying ; Guo, Xue-Ran ; Wu, Yang-Tao ; Kang, Xiao-Zhen ; Zheng, Qing-Bing ; Qi, Ruo-Yao ; Chen, Bin-Bing ; Lan, Ying ; Wei, Min ; Wang, Shao-Juan ; Xiong, Hua-Long ; Cao, Jia-Li ; Zhang, Bao-Hui ; Qiao, Xiao-Yang ; Huang, Xiao-Fen ; Wang, Ying-Bin ; Fang, Mu-Jin ; Zhang, Ya-Li ; Cheng, Tong ; Chen, Yi-Xin ; Zhao, Qin-Jian ; Li, Shao-Wei ; Ge, Sheng-Xiang ; Chen, Pei-Jer ; Zhang, Jun ; Yuan, Quan ; Xia, Ning-shao</creatorcontrib><description>ObjectiveThis study aimed to develop a novel therapeutic vaccine based on a unique B cell epitope and investigate its therapeutic potential against chronic hepatitis B (CHB) in animal models.MethodsA series of peptides and carrier proteins were evaluated in HBV-tolerant mice to obtain an optimised therapeutic molecule. The immunogenicity, therapeutic efficacy and mechanism of the candidate were investigated systematically.ResultsAmong the HBsAg-aa119-125-containing peptides evaluated in this study, HBsAg-aa113-135 (SEQ13) exhibited the most striking therapeutic effects. A novel immunoenhanced virus-like particle carrier (CR-T3) derived from the roundleaf bat HBV core antigen (RBHBcAg) was created and used to display SEQ13, forming candidate molecule CR-T3-SEQ13. Multiple copies of SEQ13 displayed on the surface of this particulate antigen promote the induction of a potent anti-HBs antibody response in mice, rabbits and cynomolgus monkeys. Sera and purified polyclonal IgG from the immunised animals neutralised HBV infection in vitro and mediated efficient HBV/hepatitis B virus surface antigen (HBsAg) clearance in the mice. CR-T3-SEQ13-based vaccination induced long-term suppression of HBsAg and HBV DNA in HBV transgenic mice and eradicated the virus completely in hydrodynamic-based HBV carrier mice. The suppressive effects on HBsAg were strongly correlated with the anti-HBs level after vaccination, suggesting that the main mechanism of CR-T3-SEQ13 vaccination therapy was the induction of a SEQ13-specific antibody response that mediated HBV/HBsAg clearance.ConclusionsThe novel particulate protein CR-T3-SEQ13 suppressed HBsAg effectively through induction of a humoural immune response in HBV-tolerant mice. This B cell epitope-based therapeutic vaccine may provide a novel immunotherapeutic agent against chronic HBV infection in humans.</description><identifier>ISSN: 0017-5749</identifier><identifier>EISSN: 1468-3288</identifier><identifier>DOI: 10.1136/gutjnl-2018-317725</identifier><identifier>PMID: 30926653</identifier><language>eng</language><publisher>England: BMJ Publishing Group Ltd and British Society of Gastroenterology</publisher><subject>Adjuvants, Immunologic ; Animal models ; Animals ; Antibody response ; Antigens ; Antiviral Agents - therapeutic use ; Chronic infection ; Combined Modality Therapy ; Core protein ; DNA, Viral - blood ; Dose-Response Relationship, Immunologic ; drug development ; Drugs ; Epitopes ; Epitopes, B-Lymphocyte - immunology ; Experiments ; Female ; Hepatitis ; hepatitis B ; Hepatitis B Antibodies - biosynthesis ; Hepatitis B surface antigen ; Hepatitis B Surface Antigens - blood ; Hepatitis B Vaccines - immunology ; Hepatitis B Vaccines - therapeutic use ; Hepatitis B virus - genetics ; Hepatitis B, Chronic - immunology ; Hepatitis B, Chronic - therapy ; Hepatitis B, Chronic - virology ; Hepatology ; Immune clearance ; Immunity, Humoral - immunology ; Immunogenicity ; Immunoglobulin G ; Immunoglobulins ; Immunotherapy ; Immunotherapy - methods ; Infections ; Laboratory animals ; Lymphocytes ; Macaca fascicularis ; Male ; Mice, Inbred BALB C ; Mice, Transgenic ; Rabbits ; Transgenic mice ; Vaccination ; Vaccines ; Viral infections ; Virus-like particles ; Viruses</subject><ispartof>Gut, 2020-02, Vol.69 (2), p.343-354</ispartof><rights>Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.</rights><rights>2020 Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ . Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b507t-f2970743ca06a14f9258421c23a681a7d84506247e2a40cc8209be262668c61d3</citedby><cites>FETCH-LOGICAL-b507t-f2970743ca06a14f9258421c23a681a7d84506247e2a40cc8209be262668c61d3</cites><orcidid>0000-0002-1638-6214 ; 0000-0003-0179-5266</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6984059/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6984059/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30926653$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Tian-Ying</creatorcontrib><creatorcontrib>Guo, Xue-Ran</creatorcontrib><creatorcontrib>Wu, Yang-Tao</creatorcontrib><creatorcontrib>Kang, Xiao-Zhen</creatorcontrib><creatorcontrib>Zheng, Qing-Bing</creatorcontrib><creatorcontrib>Qi, Ruo-Yao</creatorcontrib><creatorcontrib>Chen, Bin-Bing</creatorcontrib><creatorcontrib>Lan, Ying</creatorcontrib><creatorcontrib>Wei, Min</creatorcontrib><creatorcontrib>Wang, Shao-Juan</creatorcontrib><creatorcontrib>Xiong, Hua-Long</creatorcontrib><creatorcontrib>Cao, Jia-Li</creatorcontrib><creatorcontrib>Zhang, Bao-Hui</creatorcontrib><creatorcontrib>Qiao, Xiao-Yang</creatorcontrib><creatorcontrib>Huang, Xiao-Fen</creatorcontrib><creatorcontrib>Wang, Ying-Bin</creatorcontrib><creatorcontrib>Fang, Mu-Jin</creatorcontrib><creatorcontrib>Zhang, Ya-Li</creatorcontrib><creatorcontrib>Cheng, Tong</creatorcontrib><creatorcontrib>Chen, Yi-Xin</creatorcontrib><creatorcontrib>Zhao, Qin-Jian</creatorcontrib><creatorcontrib>Li, Shao-Wei</creatorcontrib><creatorcontrib>Ge, Sheng-Xiang</creatorcontrib><creatorcontrib>Chen, Pei-Jer</creatorcontrib><creatorcontrib>Zhang, Jun</creatorcontrib><creatorcontrib>Yuan, Quan</creatorcontrib><creatorcontrib>Xia, Ning-shao</creatorcontrib><title>A unique B cell epitope-based particulate vaccine shows effective suppression of hepatitis B surface antigen in mice</title><title>Gut</title><addtitle>Gut</addtitle><addtitle>Gut</addtitle><description>ObjectiveThis study aimed to develop a novel therapeutic vaccine based on a unique B cell epitope and investigate its therapeutic potential against chronic hepatitis B (CHB) in animal models.MethodsA series of peptides and carrier proteins were evaluated in HBV-tolerant mice to obtain an optimised therapeutic molecule. The immunogenicity, therapeutic efficacy and mechanism of the candidate were investigated systematically.ResultsAmong the HBsAg-aa119-125-containing peptides evaluated in this study, HBsAg-aa113-135 (SEQ13) exhibited the most striking therapeutic effects. A novel immunoenhanced virus-like particle carrier (CR-T3) derived from the roundleaf bat HBV core antigen (RBHBcAg) was created and used to display SEQ13, forming candidate molecule CR-T3-SEQ13. Multiple copies of SEQ13 displayed on the surface of this particulate antigen promote the induction of a potent anti-HBs antibody response in mice, rabbits and cynomolgus monkeys. Sera and purified polyclonal IgG from the immunised animals neutralised HBV infection in vitro and mediated efficient HBV/hepatitis B virus surface antigen (HBsAg) clearance in the mice. CR-T3-SEQ13-based vaccination induced long-term suppression of HBsAg and HBV DNA in HBV transgenic mice and eradicated the virus completely in hydrodynamic-based HBV carrier mice. The suppressive effects on HBsAg were strongly correlated with the anti-HBs level after vaccination, suggesting that the main mechanism of CR-T3-SEQ13 vaccination therapy was the induction of a SEQ13-specific antibody response that mediated HBV/HBsAg clearance.ConclusionsThe novel particulate protein CR-T3-SEQ13 suppressed HBsAg effectively through induction of a humoural immune response in HBV-tolerant mice. This B cell epitope-based therapeutic vaccine may provide a novel immunotherapeutic agent against chronic HBV infection in humans.</description><subject>Adjuvants, Immunologic</subject><subject>Animal models</subject><subject>Animals</subject><subject>Antibody response</subject><subject>Antigens</subject><subject>Antiviral Agents - therapeutic use</subject><subject>Chronic infection</subject><subject>Combined Modality Therapy</subject><subject>Core protein</subject><subject>DNA, Viral - blood</subject><subject>Dose-Response Relationship, Immunologic</subject><subject>drug development</subject><subject>Drugs</subject><subject>Epitopes</subject><subject>Epitopes, B-Lymphocyte - immunology</subject><subject>Experiments</subject><subject>Female</subject><subject>Hepatitis</subject><subject>hepatitis B</subject><subject>Hepatitis B Antibodies - biosynthesis</subject><subject>Hepatitis B surface antigen</subject><subject>Hepatitis B Surface Antigens - blood</subject><subject>Hepatitis B Vaccines - immunology</subject><subject>Hepatitis B Vaccines - therapeutic use</subject><subject>Hepatitis B virus - genetics</subject><subject>Hepatitis B, Chronic - immunology</subject><subject>Hepatitis B, Chronic - therapy</subject><subject>Hepatitis B, Chronic - virology</subject><subject>Hepatology</subject><subject>Immune clearance</subject><subject>Immunity, Humoral - immunology</subject><subject>Immunogenicity</subject><subject>Immunoglobulin G</subject><subject>Immunoglobulins</subject><subject>Immunotherapy</subject><subject>Immunotherapy - methods</subject><subject>Infections</subject><subject>Laboratory animals</subject><subject>Lymphocytes</subject><subject>Macaca fascicularis</subject><subject>Male</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Transgenic</subject><subject>Rabbits</subject><subject>Transgenic mice</subject><subject>Vaccination</subject><subject>Vaccines</subject><subject>Viral infections</subject><subject>Virus-like particles</subject><subject>Viruses</subject><issn>0017-5749</issn><issn>1468-3288</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>9YT</sourceid><sourceid>ACMMV</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqNkUuLFDEUhYMoTjv6B1xIwI2bGpNUKo-NMA6-YMCNrkMqfas7TVVSJqke_PemqbF9LMRVuOQ7h3vuQeg5JVeUtuL1bimHMDaMUNW0VErWPUAbykWdmFIP0YYQKptOcn2BnuR8IIQopeljdNESzYTo2g0q13gJ_tsC-C12MI4YZl_iDE1vM2zxbFPxbhltAXy0zvkAOO_jXcYwDOCKP9Z5mecEOfsYcBzwHmZbfPG5OuYlDdYBtqH4HQTsA568g6fo0WDHDM_u30v09f27Lzcfm9vPHz7dXN82fUdkaQamJZG8dZYIS_mgWac4o461Vihq5VbxjgjGJTDLiXOKEd0DEzWacoJu20v0ZvWdl36CrYNQkh3NnPxk03cTrTd__gS_N7t4NEIrTjpdDV7dG6RYb5SLmXw-nckGiEs2jBEiFWGaVvTlX-ghLinUeIa1XLGOdlJViq2USzHnBMN5GUrMqVSzlmpOpZq11Cp68XuMs-RnixVoVqCfDv9nePWLP6_5D8EPyAq8sQ</recordid><startdate>20200201</startdate><enddate>20200201</enddate><creator>Zhang, Tian-Ying</creator><creator>Guo, Xue-Ran</creator><creator>Wu, Yang-Tao</creator><creator>Kang, Xiao-Zhen</creator><creator>Zheng, Qing-Bing</creator><creator>Qi, Ruo-Yao</creator><creator>Chen, Bin-Bing</creator><creator>Lan, Ying</creator><creator>Wei, Min</creator><creator>Wang, Shao-Juan</creator><creator>Xiong, Hua-Long</creator><creator>Cao, Jia-Li</creator><creator>Zhang, Bao-Hui</creator><creator>Qiao, Xiao-Yang</creator><creator>Huang, Xiao-Fen</creator><creator>Wang, Ying-Bin</creator><creator>Fang, Mu-Jin</creator><creator>Zhang, Ya-Li</creator><creator>Cheng, Tong</creator><creator>Chen, Yi-Xin</creator><creator>Zhao, Qin-Jian</creator><creator>Li, Shao-Wei</creator><creator>Ge, Sheng-Xiang</creator><creator>Chen, Pei-Jer</creator><creator>Zhang, Jun</creator><creator>Yuan, Quan</creator><creator>Xia, Ning-shao</creator><general>BMJ Publishing Group Ltd and British Society of Gastroenterology</general><general>BMJ Publishing Group LTD</general><general>BMJ Publishing Group</general><scope>9YT</scope><scope>ACMMV</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>BTHHO</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-1638-6214</orcidid><orcidid>https://orcid.org/0000-0003-0179-5266</orcidid></search><sort><creationdate>20200201</creationdate><title>A unique B cell epitope-based particulate vaccine shows effective suppression of hepatitis B surface antigen in mice</title><author>Zhang, Tian-Ying ; Guo, Xue-Ran ; Wu, Yang-Tao ; Kang, Xiao-Zhen ; Zheng, Qing-Bing ; Qi, Ruo-Yao ; Chen, Bin-Bing ; Lan, Ying ; Wei, Min ; Wang, Shao-Juan ; Xiong, Hua-Long ; Cao, Jia-Li ; Zhang, Bao-Hui ; Qiao, Xiao-Yang ; Huang, Xiao-Fen ; Wang, Ying-Bin ; Fang, Mu-Jin ; Zhang, Ya-Li ; Cheng, Tong ; Chen, Yi-Xin ; Zhao, Qin-Jian ; Li, Shao-Wei ; Ge, Sheng-Xiang ; Chen, Pei-Jer ; Zhang, Jun ; Yuan, Quan ; Xia, Ning-shao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b507t-f2970743ca06a14f9258421c23a681a7d84506247e2a40cc8209be262668c61d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adjuvants, Immunologic</topic><topic>Animal models</topic><topic>Animals</topic><topic>Antibody response</topic><topic>Antigens</topic><topic>Antiviral Agents - therapeutic use</topic><topic>Chronic infection</topic><topic>Combined Modality Therapy</topic><topic>Core protein</topic><topic>DNA, Viral - blood</topic><topic>Dose-Response Relationship, Immunologic</topic><topic>drug development</topic><topic>Drugs</topic><topic>Epitopes</topic><topic>Epitopes, B-Lymphocyte - immunology</topic><topic>Experiments</topic><topic>Female</topic><topic>Hepatitis</topic><topic>hepatitis B</topic><topic>Hepatitis B Antibodies - biosynthesis</topic><topic>Hepatitis B surface antigen</topic><topic>Hepatitis B Surface Antigens - blood</topic><topic>Hepatitis B Vaccines - immunology</topic><topic>Hepatitis B Vaccines - therapeutic use</topic><topic>Hepatitis B virus - genetics</topic><topic>Hepatitis B, Chronic - immunology</topic><topic>Hepatitis B, Chronic - therapy</topic><topic>Hepatitis B, Chronic - virology</topic><topic>Hepatology</topic><topic>Immune clearance</topic><topic>Immunity, Humoral - immunology</topic><topic>Immunogenicity</topic><topic>Immunoglobulin G</topic><topic>Immunoglobulins</topic><topic>Immunotherapy</topic><topic>Immunotherapy - methods</topic><topic>Infections</topic><topic>Laboratory animals</topic><topic>Lymphocytes</topic><topic>Macaca fascicularis</topic><topic>Male</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Transgenic</topic><topic>Rabbits</topic><topic>Transgenic mice</topic><topic>Vaccination</topic><topic>Vaccines</topic><topic>Viral infections</topic><topic>Virus-like particles</topic><topic>Viruses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Tian-Ying</creatorcontrib><creatorcontrib>Guo, Xue-Ran</creatorcontrib><creatorcontrib>Wu, Yang-Tao</creatorcontrib><creatorcontrib>Kang, Xiao-Zhen</creatorcontrib><creatorcontrib>Zheng, Qing-Bing</creatorcontrib><creatorcontrib>Qi, Ruo-Yao</creatorcontrib><creatorcontrib>Chen, Bin-Bing</creatorcontrib><creatorcontrib>Lan, Ying</creatorcontrib><creatorcontrib>Wei, Min</creatorcontrib><creatorcontrib>Wang, Shao-Juan</creatorcontrib><creatorcontrib>Xiong, Hua-Long</creatorcontrib><creatorcontrib>Cao, Jia-Li</creatorcontrib><creatorcontrib>Zhang, Bao-Hui</creatorcontrib><creatorcontrib>Qiao, Xiao-Yang</creatorcontrib><creatorcontrib>Huang, Xiao-Fen</creatorcontrib><creatorcontrib>Wang, Ying-Bin</creatorcontrib><creatorcontrib>Fang, Mu-Jin</creatorcontrib><creatorcontrib>Zhang, Ya-Li</creatorcontrib><creatorcontrib>Cheng, Tong</creatorcontrib><creatorcontrib>Chen, Yi-Xin</creatorcontrib><creatorcontrib>Zhao, Qin-Jian</creatorcontrib><creatorcontrib>Li, Shao-Wei</creatorcontrib><creatorcontrib>Ge, Sheng-Xiang</creatorcontrib><creatorcontrib>Chen, Pei-Jer</creatorcontrib><creatorcontrib>Zhang, Jun</creatorcontrib><creatorcontrib>Yuan, Quan</creatorcontrib><creatorcontrib>Xia, Ning-shao</creatorcontrib><collection>BMJ Open Access Journals</collection><collection>BMJ Journals:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>BMJ Journals</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Gut</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Tian-Ying</au><au>Guo, Xue-Ran</au><au>Wu, Yang-Tao</au><au>Kang, Xiao-Zhen</au><au>Zheng, Qing-Bing</au><au>Qi, Ruo-Yao</au><au>Chen, Bin-Bing</au><au>Lan, Ying</au><au>Wei, Min</au><au>Wang, Shao-Juan</au><au>Xiong, Hua-Long</au><au>Cao, Jia-Li</au><au>Zhang, Bao-Hui</au><au>Qiao, Xiao-Yang</au><au>Huang, Xiao-Fen</au><au>Wang, Ying-Bin</au><au>Fang, Mu-Jin</au><au>Zhang, Ya-Li</au><au>Cheng, Tong</au><au>Chen, Yi-Xin</au><au>Zhao, Qin-Jian</au><au>Li, Shao-Wei</au><au>Ge, Sheng-Xiang</au><au>Chen, Pei-Jer</au><au>Zhang, Jun</au><au>Yuan, Quan</au><au>Xia, Ning-shao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A unique B cell epitope-based particulate vaccine shows effective suppression of hepatitis B surface antigen in mice</atitle><jtitle>Gut</jtitle><stitle>Gut</stitle><addtitle>Gut</addtitle><date>2020-02-01</date><risdate>2020</risdate><volume>69</volume><issue>2</issue><spage>343</spage><epage>354</epage><pages>343-354</pages><issn>0017-5749</issn><eissn>1468-3288</eissn><abstract>ObjectiveThis study aimed to develop a novel therapeutic vaccine based on a unique B cell epitope and investigate its therapeutic potential against chronic hepatitis B (CHB) in animal models.MethodsA series of peptides and carrier proteins were evaluated in HBV-tolerant mice to obtain an optimised therapeutic molecule. The immunogenicity, therapeutic efficacy and mechanism of the candidate were investigated systematically.ResultsAmong the HBsAg-aa119-125-containing peptides evaluated in this study, HBsAg-aa113-135 (SEQ13) exhibited the most striking therapeutic effects. A novel immunoenhanced virus-like particle carrier (CR-T3) derived from the roundleaf bat HBV core antigen (RBHBcAg) was created and used to display SEQ13, forming candidate molecule CR-T3-SEQ13. Multiple copies of SEQ13 displayed on the surface of this particulate antigen promote the induction of a potent anti-HBs antibody response in mice, rabbits and cynomolgus monkeys. Sera and purified polyclonal IgG from the immunised animals neutralised HBV infection in vitro and mediated efficient HBV/hepatitis B virus surface antigen (HBsAg) clearance in the mice. CR-T3-SEQ13-based vaccination induced long-term suppression of HBsAg and HBV DNA in HBV transgenic mice and eradicated the virus completely in hydrodynamic-based HBV carrier mice. The suppressive effects on HBsAg were strongly correlated with the anti-HBs level after vaccination, suggesting that the main mechanism of CR-T3-SEQ13 vaccination therapy was the induction of a SEQ13-specific antibody response that mediated HBV/HBsAg clearance.ConclusionsThe novel particulate protein CR-T3-SEQ13 suppressed HBsAg effectively through induction of a humoural immune response in HBV-tolerant mice. This B cell epitope-based therapeutic vaccine may provide a novel immunotherapeutic agent against chronic HBV infection in humans.</abstract><cop>England</cop><pub>BMJ Publishing Group Ltd and British Society of Gastroenterology</pub><pmid>30926653</pmid><doi>10.1136/gutjnl-2018-317725</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-1638-6214</orcidid><orcidid>https://orcid.org/0000-0003-0179-5266</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0017-5749 |
| ispartof | Gut, 2020-02, Vol.69 (2), p.343-354 |
| issn | 0017-5749 1468-3288 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6984059 |
| source | MEDLINE; PubMed Central |
| subjects | Adjuvants, Immunologic Animal models Animals Antibody response Antigens Antiviral Agents - therapeutic use Chronic infection Combined Modality Therapy Core protein DNA, Viral - blood Dose-Response Relationship, Immunologic drug development Drugs Epitopes Epitopes, B-Lymphocyte - immunology Experiments Female Hepatitis hepatitis B Hepatitis B Antibodies - biosynthesis Hepatitis B surface antigen Hepatitis B Surface Antigens - blood Hepatitis B Vaccines - immunology Hepatitis B Vaccines - therapeutic use Hepatitis B virus - genetics Hepatitis B, Chronic - immunology Hepatitis B, Chronic - therapy Hepatitis B, Chronic - virology Hepatology Immune clearance Immunity, Humoral - immunology Immunogenicity Immunoglobulin G Immunoglobulins Immunotherapy Immunotherapy - methods Infections Laboratory animals Lymphocytes Macaca fascicularis Male Mice, Inbred BALB C Mice, Transgenic Rabbits Transgenic mice Vaccination Vaccines Viral infections Virus-like particles Viruses |
| title | A unique B cell epitope-based particulate vaccine shows effective suppression of hepatitis B surface antigen in mice |
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