Enhanced vaccine-induced CD8+ T cell responses to malaria antigen ME-TRAP by fusion to MHC class ii invariant chain
The orthodox role of the invariant chain (CD74; Ii) is in antigen presentation to CD4+ T cells, but enhanced CD8+ T cells responses have been reported after vaccination with vectored viral vaccines encoding a fusion of Ii to the antigen of interest. In this study we assessed whether fusion of the ma...
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| creator | Spencer, Alexandra J Cottingham, Matthew G Jenks, Jennifer A Longley, Rhea J Capone, Stefania Colloca, Stefano Folgori, Antonella Cortese, Riccardo Nicosia, Alfredo Bregu, Migena Hill, Adrian V S |
| description | The orthodox role of the invariant chain (CD74; Ii) is in antigen presentation to CD4+ T cells, but enhanced CD8+ T cells responses have been reported after vaccination with vectored viral vaccines encoding a fusion of Ii to the antigen of interest. In this study we assessed whether fusion of the malarial antigen, ME-TRAP, to Ii could increase the vaccine-induced CD8+ T cell response. Following single or heterologous prime-boost vaccination of mice with a recombinant chimpanzee adenovirus vector, ChAd63, or recombinant modified vaccinia virus Ankara (MVA), higher frequencies of antigen-specific CD4+ and CD8+ T cells were observed, with the largest increases observed following a ChAd63-MVA heterologous prime-boost regimen. Studies in non-human primates confirmed the ability of Ii-fusion to augment the T cell response, where a 4-fold increase was maintained up to 11 weeks after the MVA boost. Of the numerous different approaches explored to increase vectored vaccine induced immunogenicity over the years, fusion to the invariant chain showed a consistent enhancement in CD8+ T cell responses across different animal species and may therefore find application in the development of vaccines against human malaria and other diseases where high levels of cell-mediated immunity are required. |
| doi_str_mv | 10.1371/journal.pone.0100538 |
| format | Article |
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In this study we assessed whether fusion of the malarial antigen, ME-TRAP, to Ii could increase the vaccine-induced CD8+ T cell response. Following single or heterologous prime-boost vaccination of mice with a recombinant chimpanzee adenovirus vector, ChAd63, or recombinant modified vaccinia virus Ankara (MVA), higher frequencies of antigen-specific CD4+ and CD8+ T cells were observed, with the largest increases observed following a ChAd63-MVA heterologous prime-boost regimen. Studies in non-human primates confirmed the ability of Ii-fusion to augment the T cell response, where a 4-fold increase was maintained up to 11 weeks after the MVA boost. Of the numerous different approaches explored to increase vectored vaccine induced immunogenicity over the years, fusion to the invariant chain showed a consistent enhancement in CD8+ T cell responses across different animal species and may therefore find application in the development of vaccines against human malaria and other diseases where high levels of cell-mediated immunity are required.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0100538</identifier><identifier>PMID: 24945248</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adenoviruses ; Animal species ; Animals ; Antigen presentation ; Antigens, Differentiation, B-Lymphocyte - immunology ; Antigens, Protozoan - immunology ; Biology and Life Sciences ; CD4 antigen ; CD8 antigen ; CD8-Positive T-Lymphocytes - immunology ; Cell-mediated immunity ; Chains ; Chickens ; Deoxyribonucleic acid ; DNA ; Female ; Genetic Vectors - metabolism ; Histocompatibility Antigens Class II - immunology ; Human performance ; Humans ; Immunity ; Immunization ; Immunogenicity ; Immunoglobulins ; Invariant chain ; Invariants ; Lymphocytes ; Lymphocytes T ; Macaca mulatta - immunology ; Major histocompatibility complex ; Malaria ; Malaria Vaccines - immunology ; Malaria, Falciparum - immunology ; Malaria, Falciparum - prevention & control ; Male ; Medical research ; Medicine and Health Sciences ; Mice, Inbred C57BL ; Mice, Inbred ICR ; Primates ; Proteins ; Recombinant Fusion Proteins - immunology ; T cell receptors ; Vaccines ; Vector-borne diseases ; Viruses</subject><ispartof>PloS one, 2014-06, Vol.9 (6), p.e100538-e100538</ispartof><rights>2014 Spencer et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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vaccine-induced CD8+ T cell responses to malaria antigen ME-TRAP by fusion to MHC class ii invariant chain</title><author>Spencer, Alexandra J ; Cottingham, Matthew G ; Jenks, Jennifer A ; Longley, Rhea J ; Capone, Stefania ; Colloca, Stefano ; Folgori, Antonella ; Cortese, Riccardo ; Nicosia, Alfredo ; Bregu, Migena ; Hill, Adrian V S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-35d9ca625486850412cd8e6b5c8e18d61a580467e918445f51bd41ea5bb43ccf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adenoviruses</topic><topic>Animal species</topic><topic>Animals</topic><topic>Antigen presentation</topic><topic>Antigens, Differentiation, B-Lymphocyte - immunology</topic><topic>Antigens, Protozoan - immunology</topic><topic>Biology and Life Sciences</topic><topic>CD4 antigen</topic><topic>CD8 antigen</topic><topic>CD8-Positive T-Lymphocytes - 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vaccine-induced CD8+ T cell responses to malaria antigen ME-TRAP by fusion to MHC class ii invariant chain</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-06-19</date><risdate>2014</risdate><volume>9</volume><issue>6</issue><spage>e100538</spage><epage>e100538</epage><pages>e100538-e100538</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The orthodox role of the invariant chain (CD74; Ii) is in antigen presentation to CD4+ T cells, but enhanced CD8+ T cells responses have been reported after vaccination with vectored viral vaccines encoding a fusion of Ii to the antigen of interest. In this study we assessed whether fusion of the malarial antigen, ME-TRAP, to Ii could increase the vaccine-induced CD8+ T cell response. Following single or heterologous prime-boost vaccination of mice with a recombinant chimpanzee adenovirus vector, ChAd63, or recombinant modified vaccinia virus Ankara (MVA), higher frequencies of antigen-specific CD4+ and CD8+ T cells were observed, with the largest increases observed following a ChAd63-MVA heterologous prime-boost regimen. Studies in non-human primates confirmed the ability of Ii-fusion to augment the T cell response, where a 4-fold increase was maintained up to 11 weeks after the MVA boost. Of the numerous different approaches explored to increase vectored vaccine induced immunogenicity over the years, fusion to the invariant chain showed a consistent enhancement in CD8+ T cell responses across different animal species and may therefore find application in the development of vaccines against human malaria and other diseases where high levels of cell-mediated immunity are required.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24945248</pmid><doi>10.1371/journal.pone.0100538</doi><oa>free_for_read</oa></addata></record> |
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| issn | 1932-6203 1932-6203 |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adenoviruses Animal species Animals Antigen presentation Antigens, Differentiation, B-Lymphocyte - immunology Antigens, Protozoan - immunology Biology and Life Sciences CD4 antigen CD8 antigen CD8-Positive T-Lymphocytes - immunology Cell-mediated immunity Chains Chickens Deoxyribonucleic acid DNA Female Genetic Vectors - metabolism Histocompatibility Antigens Class II - immunology Human performance Humans Immunity Immunization Immunogenicity Immunoglobulins Invariant chain Invariants Lymphocytes Lymphocytes T Macaca mulatta - immunology Major histocompatibility complex Malaria Malaria Vaccines - immunology Malaria, Falciparum - immunology Malaria, Falciparum - prevention & control Male Medical research Medicine and Health Sciences Mice, Inbred C57BL Mice, Inbred ICR Primates Proteins Recombinant Fusion Proteins - immunology T cell receptors Vaccines Vector-borne diseases Viruses |
| title | Enhanced vaccine-induced CD8+ T cell responses to malaria antigen ME-TRAP by fusion to MHC class ii invariant chain |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-19T13%3A21%3A37IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Enhanced%20vaccine-induced%20CD8+%20T%20cell%20responses%20to%20malaria%20antigen%20ME-TRAP%20by%20fusion%20to%20MHC%20class%20ii%20invariant%20chain&rft.jtitle=PloS%20one&rft.au=Spencer,%20Alexandra%20J&rft.date=2014-06-19&rft.volume=9&rft.issue=6&rft.spage=e100538&rft.epage=e100538&rft.pages=e100538-e100538&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0100538&rft_dat=%3Cproquest_plos_%3E1539707088%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1537651337&rft_id=info:pmid/24945248&rft_doaj_id=oai_doaj_org_article_03a908736103413081ed60360973a6cb&rfr_iscdi=true |