Construction and immunogenicity of a T cell epitope-based subunit vaccine candidate against Mycobacterium tuberculosis
•This study is the first to design a tuberculosis vaccine based on T cell epitopes.•T cell epitope-based subunit vaccinestimulated strong Th1-type cellular immune response.•The used approach could be useful against latent TB. Despite antibiotic treatment and Bacille Calmette-Guérin (BCG) vaccination...
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| Veröffentlicht in: | Vaccine 2021-11, Vol.39 (47), p.6860-6865 |
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| container_title | Vaccine |
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| creator | Fan, Xueting Li, Xiaoyan Wan, Kanglin Zhao, Xiuqin Deng, Yunli Chen, Zixin Luan, Xiuli Lu, Shuangshuang Liu, Haican |
| description | •This study is the first to design a tuberculosis vaccine based on T cell epitopes.•T cell epitope-based subunit vaccinestimulated strong Th1-type cellular immune response.•The used approach could be useful against latent TB.
Despite antibiotic treatment and Bacille Calmette-Guérin (BCG) vaccination, Mycobacterium tuberculosis remains a major public health burden in most developing countries. Therefore, developing an improved vaccine is high priority. In this study, we cloned the genes of the immunodominant antigen of M. tuberculosis viz. its 38-kDa antigen (Pst homolog) (Rv0934, PstS1), and its T cell epitopes (amino acid [aa]169–405 and [aa]802–1119), which we termed PstS1p. Prokaryotic expression showed that the two recombinant proteins were mainly in the form of inclusion bodies. We also evaluated the immunity and immunogenicity of PstS1 and PstS1p. Both PstS1 and its T cell epitopes elicited significantly higher antigen-specific immunoglobulin G (IgG) antibodies in mouse serum, indicating that they enhanced antibody response. They also elicited the T helper 1 (Th1)-type response and promoted CD4+ T cell proliferation. Compared to PstS1, PstS1p promoted stronger cell-mediated immune response. These data indicate that PstS1p is highly immunogenic in mice, and may be a promising candidate vaccine for controlling tuberculosis. |
| doi_str_mv | 10.1016/j.vaccine.2021.10.034 |
| format | Article |
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Despite antibiotic treatment and Bacille Calmette-Guérin (BCG) vaccination, Mycobacterium tuberculosis remains a major public health burden in most developing countries. Therefore, developing an improved vaccine is high priority. In this study, we cloned the genes of the immunodominant antigen of M. tuberculosis viz. its 38-kDa antigen (Pst homolog) (Rv0934, PstS1), and its T cell epitopes (amino acid [aa]169–405 and [aa]802–1119), which we termed PstS1p. Prokaryotic expression showed that the two recombinant proteins were mainly in the form of inclusion bodies. We also evaluated the immunity and immunogenicity of PstS1 and PstS1p. Both PstS1 and its T cell epitopes elicited significantly higher antigen-specific immunoglobulin G (IgG) antibodies in mouse serum, indicating that they enhanced antibody response. They also elicited the T helper 1 (Th1)-type response and promoted CD4+ T cell proliferation. Compared to PstS1, PstS1p promoted stronger cell-mediated immune response. These data indicate that PstS1p is highly immunogenic in mice, and may be a promising candidate vaccine for controlling tuberculosis.</description><identifier>ISSN: 0264-410X</identifier><identifier>EISSN: 1873-2518</identifier><identifier>DOI: 10.1016/j.vaccine.2021.10.034</identifier><identifier>PMID: 34702619</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Amino acids ; Animals ; Antibiotics ; Antibody response ; Antigens ; Antigens, Bacterial - genetics ; Bacterial Proteins - genetics ; BCG Vaccine ; CD4 antigen ; Cell proliferation ; Cloning ; Cytokines ; Developing countries ; Disease control ; Epitopes ; Epitopes, T-Lymphocyte ; Flow cytometry ; Homology ; IgG antibody ; Immune response ; Immune response (cell-mediated) ; Immune system ; Immunodominance ; Immunogenicity ; Immunoglobulin G ; Inclusion bodies ; LDCs ; Lymphocytes ; Lymphocytes T ; Mice ; Mycobacterium bovis ; Mycobacterium tuberculosis ; Proteins ; PstS1 ; Public health ; T cell epitopes ; TB vaccine ; Tuberculosis ; Tuberculosis Vaccines ; Tumor necrosis factor-TNF ; Vaccination ; Vaccines ; Vaccines, Subunit</subject><ispartof>Vaccine, 2021-11, Vol.39 (47), p.6860-6865</ispartof><rights>2021</rights><rights>Copyright © 2021. Published by Elsevier Ltd.</rights><rights>Copyright Elsevier Limited Nov 16, 2021</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c393t-a6cff4b8aafc24e3399b8a82ff0b92c9a65f7d6425ffa57e57ac993201611d323</citedby><cites>FETCH-LOGICAL-c393t-a6cff4b8aafc24e3399b8a82ff0b92c9a65f7d6425ffa57e57ac993201611d323</cites><orcidid>0000-0002-9420-1211 ; 0000-0003-3272-5877</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0264410X21013542$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34702619$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fan, Xueting</creatorcontrib><creatorcontrib>Li, Xiaoyan</creatorcontrib><creatorcontrib>Wan, Kanglin</creatorcontrib><creatorcontrib>Zhao, Xiuqin</creatorcontrib><creatorcontrib>Deng, Yunli</creatorcontrib><creatorcontrib>Chen, Zixin</creatorcontrib><creatorcontrib>Luan, Xiuli</creatorcontrib><creatorcontrib>Lu, Shuangshuang</creatorcontrib><creatorcontrib>Liu, Haican</creatorcontrib><title>Construction and immunogenicity of a T cell epitope-based subunit vaccine candidate against Mycobacterium tuberculosis</title><title>Vaccine</title><addtitle>Vaccine</addtitle><description>•This study is the first to design a tuberculosis vaccine based on T cell epitopes.•T cell epitope-based subunit vaccinestimulated strong Th1-type cellular immune response.•The used approach could be useful against latent TB.
Despite antibiotic treatment and Bacille Calmette-Guérin (BCG) vaccination, Mycobacterium tuberculosis remains a major public health burden in most developing countries. Therefore, developing an improved vaccine is high priority. In this study, we cloned the genes of the immunodominant antigen of M. tuberculosis viz. its 38-kDa antigen (Pst homolog) (Rv0934, PstS1), and its T cell epitopes (amino acid [aa]169–405 and [aa]802–1119), which we termed PstS1p. Prokaryotic expression showed that the two recombinant proteins were mainly in the form of inclusion bodies. We also evaluated the immunity and immunogenicity of PstS1 and PstS1p. Both PstS1 and its T cell epitopes elicited significantly higher antigen-specific immunoglobulin G (IgG) antibodies in mouse serum, indicating that they enhanced antibody response. They also elicited the T helper 1 (Th1)-type response and promoted CD4+ T cell proliferation. Compared to PstS1, PstS1p promoted stronger cell-mediated immune response. These data indicate that PstS1p is highly immunogenic in mice, and may be a promising candidate vaccine for controlling tuberculosis.</description><subject>Amino acids</subject><subject>Animals</subject><subject>Antibiotics</subject><subject>Antibody response</subject><subject>Antigens</subject><subject>Antigens, Bacterial - genetics</subject><subject>Bacterial Proteins - genetics</subject><subject>BCG Vaccine</subject><subject>CD4 antigen</subject><subject>Cell proliferation</subject><subject>Cloning</subject><subject>Cytokines</subject><subject>Developing countries</subject><subject>Disease control</subject><subject>Epitopes</subject><subject>Epitopes, T-Lymphocyte</subject><subject>Flow cytometry</subject><subject>Homology</subject><subject>IgG antibody</subject><subject>Immune response</subject><subject>Immune response (cell-mediated)</subject><subject>Immune system</subject><subject>Immunodominance</subject><subject>Immunogenicity</subject><subject>Immunoglobulin G</subject><subject>Inclusion bodies</subject><subject>LDCs</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Mice</subject><subject>Mycobacterium bovis</subject><subject>Mycobacterium tuberculosis</subject><subject>Proteins</subject><subject>PstS1</subject><subject>Public health</subject><subject>T cell epitopes</subject><subject>TB vaccine</subject><subject>Tuberculosis</subject><subject>Tuberculosis Vaccines</subject><subject>Tumor necrosis factor-TNF</subject><subject>Vaccination</subject><subject>Vaccines</subject><subject>Vaccines, Subunit</subject><issn>0264-410X</issn><issn>1873-2518</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFkUtvEzEUhS0EoqHwE0CW2LCZ1M-Z8QqhqDykVt20EjvL47muHGXs4Eek_HscJbBgw8ry9XfuvT4HofeUrCmh_c12fTDW-gBrRhhttTXh4gVa0XHgHZN0fIlWhPWiE5T8vEJvct4SQiSn6jW64mJob1St0GETQy6p2uJjwCbM2C9LDfEZgre-HHF02OBHbGG3w7D3Je6hm0yGGec61eALvuyBbVP72RTA5tn41hXfH22cjC2QfF1wqRMkW3cx-_wWvXJml-Hd5bxGT19vHzffu7uHbz82X-46yxUvnemtc2IajXGWCeBcqXYZmXNkUswq00s3zL1g0jkjB5CDsUpx1gyidOaMX6NP5777FH9VyEUvPp_-YgLEmjWTY98EQsiGfvwH3caaQtuuUaoXzVJCGiXPlE0x5wRO75NfTDpqSvQpGL3VF0P0KZhTuQXTdB8u3eu0wPxX9SeJBnw-A9DsOHhIOlsPwcLsE9ii5-j_M-I3zUOjmQ</recordid><startdate>20211116</startdate><enddate>20211116</enddate><creator>Fan, Xueting</creator><creator>Li, Xiaoyan</creator><creator>Wan, Kanglin</creator><creator>Zhao, Xiuqin</creator><creator>Deng, Yunli</creator><creator>Chen, Zixin</creator><creator>Luan, Xiuli</creator><creator>Lu, Shuangshuang</creator><creator>Liu, Haican</creator><general>Elsevier Ltd</general><general>Elsevier Limited</general><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>7QL</scope><scope>7RV</scope><scope>7T2</scope><scope>7T5</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88C</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0R</scope><scope>M0S</scope><scope>M0T</scope><scope>M1P</scope><scope>M2O</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-9420-1211</orcidid><orcidid>https://orcid.org/0000-0003-3272-5877</orcidid></search><sort><creationdate>20211116</creationdate><title>Construction and immunogenicity of a T cell epitope-based subunit vaccine candidate against Mycobacterium tuberculosis</title><author>Fan, Xueting ; Li, Xiaoyan ; Wan, Kanglin ; Zhao, Xiuqin ; Deng, Yunli ; Chen, Zixin ; Luan, Xiuli ; Lu, Shuangshuang ; Liu, Haican</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c393t-a6cff4b8aafc24e3399b8a82ff0b92c9a65f7d6425ffa57e57ac993201611d323</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Amino acids</topic><topic>Animals</topic><topic>Antibiotics</topic><topic>Antibody response</topic><topic>Antigens</topic><topic>Antigens, Bacterial - genetics</topic><topic>Bacterial Proteins - genetics</topic><topic>BCG Vaccine</topic><topic>CD4 antigen</topic><topic>Cell proliferation</topic><topic>Cloning</topic><topic>Cytokines</topic><topic>Developing countries</topic><topic>Disease control</topic><topic>Epitopes</topic><topic>Epitopes, T-Lymphocyte</topic><topic>Flow cytometry</topic><topic>Homology</topic><topic>IgG antibody</topic><topic>Immune response</topic><topic>Immune response (cell-mediated)</topic><topic>Immune system</topic><topic>Immunodominance</topic><topic>Immunogenicity</topic><topic>Immunoglobulin G</topic><topic>Inclusion bodies</topic><topic>LDCs</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Mice</topic><topic>Mycobacterium bovis</topic><topic>Mycobacterium tuberculosis</topic><topic>Proteins</topic><topic>PstS1</topic><topic>Public health</topic><topic>T cell epitopes</topic><topic>TB vaccine</topic><topic>Tuberculosis</topic><topic>Tuberculosis Vaccines</topic><topic>Tumor necrosis factor-TNF</topic><topic>Vaccination</topic><topic>Vaccines</topic><topic>Vaccines, Subunit</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fan, Xueting</creatorcontrib><creatorcontrib>Li, Xiaoyan</creatorcontrib><creatorcontrib>Wan, Kanglin</creatorcontrib><creatorcontrib>Zhao, Xiuqin</creatorcontrib><creatorcontrib>Deng, Yunli</creatorcontrib><creatorcontrib>Chen, Zixin</creatorcontrib><creatorcontrib>Luan, Xiuli</creatorcontrib><creatorcontrib>Lu, Shuangshuang</creatorcontrib><creatorcontrib>Liu, Haican</creatorcontrib><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>Bacteriology Abstracts (Microbiology B)</collection><collection>Nursing & Allied Health Database</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Healthcare Administration Database (Alumni)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health 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>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</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>Environmental Sciences and Pollution Management</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>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Healthcare Administration Database</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</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><jtitle>Vaccine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fan, Xueting</au><au>Li, Xiaoyan</au><au>Wan, Kanglin</au><au>Zhao, Xiuqin</au><au>Deng, Yunli</au><au>Chen, Zixin</au><au>Luan, Xiuli</au><au>Lu, Shuangshuang</au><au>Liu, Haican</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Construction and immunogenicity of a T cell epitope-based subunit vaccine candidate against Mycobacterium tuberculosis</atitle><jtitle>Vaccine</jtitle><addtitle>Vaccine</addtitle><date>2021-11-16</date><risdate>2021</risdate><volume>39</volume><issue>47</issue><spage>6860</spage><epage>6865</epage><pages>6860-6865</pages><issn>0264-410X</issn><eissn>1873-2518</eissn><abstract>•This study is the first to design a tuberculosis vaccine based on T cell epitopes.•T cell epitope-based subunit vaccinestimulated strong Th1-type cellular immune response.•The used approach could be useful against latent TB.
Despite antibiotic treatment and Bacille Calmette-Guérin (BCG) vaccination, Mycobacterium tuberculosis remains a major public health burden in most developing countries. Therefore, developing an improved vaccine is high priority. In this study, we cloned the genes of the immunodominant antigen of M. tuberculosis viz. its 38-kDa antigen (Pst homolog) (Rv0934, PstS1), and its T cell epitopes (amino acid [aa]169–405 and [aa]802–1119), which we termed PstS1p. Prokaryotic expression showed that the two recombinant proteins were mainly in the form of inclusion bodies. We also evaluated the immunity and immunogenicity of PstS1 and PstS1p. Both PstS1 and its T cell epitopes elicited significantly higher antigen-specific immunoglobulin G (IgG) antibodies in mouse serum, indicating that they enhanced antibody response. They also elicited the T helper 1 (Th1)-type response and promoted CD4+ T cell proliferation. Compared to PstS1, PstS1p promoted stronger cell-mediated immune response. These data indicate that PstS1p is highly immunogenic in mice, and may be a promising candidate vaccine for controlling tuberculosis.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>34702619</pmid><doi>10.1016/j.vaccine.2021.10.034</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0002-9420-1211</orcidid><orcidid>https://orcid.org/0000-0003-3272-5877</orcidid></addata></record> |
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| ispartof | Vaccine, 2021-11, Vol.39 (47), p.6860-6865 |
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| subjects | Amino acids Animals Antibiotics Antibody response Antigens Antigens, Bacterial - genetics Bacterial Proteins - genetics BCG Vaccine CD4 antigen Cell proliferation Cloning Cytokines Developing countries Disease control Epitopes Epitopes, T-Lymphocyte Flow cytometry Homology IgG antibody Immune response Immune response (cell-mediated) Immune system Immunodominance Immunogenicity Immunoglobulin G Inclusion bodies LDCs Lymphocytes Lymphocytes T Mice Mycobacterium bovis Mycobacterium tuberculosis Proteins PstS1 Public health T cell epitopes TB vaccine Tuberculosis Tuberculosis Vaccines Tumor necrosis factor-TNF Vaccination Vaccines Vaccines, Subunit |
| title | Construction and immunogenicity of a T cell epitope-based subunit vaccine candidate against Mycobacterium tuberculosis |
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