Recombinant nucleocapsid-like particles from dengue-2 virus induce protective CD4+ and CD8+ cells against viral encephalitis in mice
Virus-like particles are a highly effective type of subunit vaccine that mimics the overall structure of virus particles without containing infectious genetic material. In this work, a particulate form of the recombinant capsid protein from dengue-2 was evaluated in mice to determine the level of pr...
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| Veröffentlicht in: | International immunology 2009-10, Vol.21 (10), p.1175-1183 |
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| container_title | International immunology |
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| creator | Gil, Lázaro López, Carlos Lazo, Laura Valdés, Iris Marcos, Ernesto Alonso, Ruby Gambe, Ailyn Martín, Jorge Romero, Yaremis Guzmán, María G. Guillén, Gerardo Hermida, Lisset |
| description | Virus-like particles are a highly effective type of subunit vaccine that mimics the overall structure of virus particles without containing infectious genetic material. In this work, a particulate form of the recombinant capsid protein from dengue-2 was evaluated in mice to determine the level of protection against viral challenge and to measure the antigen-induced cell-mediated immunity (CMI). The nucleocapsid-like particles (NLPs) adjuvanted with alum did not induce antiviral antibodies. However, splenocytes from the immunized animals secreted high levels of IFN-γ upon virus stimulation, and a significant protection rate was achieved after challenge with lethal dengue-2 virus. Finally, both IFN-γ secretion and protection against viral encephalitis were demonstrated to be dependent on CD4+ and CD8+ cells. This study provides new evidences regarding the protective role of the CMI in the mouse model without the induction of neutralizing antibodies. Further studies in non-human primates or humanized mice should be carried out to elucidate the usefulness of the NLPs as a potential vaccine candidate against dengue disease. |
| doi_str_mv | 10.1093/intimm/dxp082 |
| format | Article |
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In this work, a particulate form of the recombinant capsid protein from dengue-2 was evaluated in mice to determine the level of protection against viral challenge and to measure the antigen-induced cell-mediated immunity (CMI). The nucleocapsid-like particles (NLPs) adjuvanted with alum did not induce antiviral antibodies. However, splenocytes from the immunized animals secreted high levels of IFN-γ upon virus stimulation, and a significant protection rate was achieved after challenge with lethal dengue-2 virus. Finally, both IFN-γ secretion and protection against viral encephalitis were demonstrated to be dependent on CD4+ and CD8+ cells. This study provides new evidences regarding the protective role of the CMI in the mouse model without the induction of neutralizing antibodies. Further studies in non-human primates or humanized mice should be carried out to elucidate the usefulness of the NLPs as a potential vaccine candidate against dengue disease.</description><identifier>ISSN: 0953-8178</identifier><identifier>EISSN: 1460-2377</identifier><identifier>DOI: 10.1093/intimm/dxp082</identifier><identifier>PMID: 19692540</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Animals ; Antibodies, Viral - blood ; capsid protein ; CD4-Positive T-Lymphocytes - immunology ; CD4-Positive T-Lymphocytes - metabolism ; CD4-Positive T-Lymphocytes - virology ; CD8-Positive T-Lymphocytes - immunology ; CD8-Positive T-Lymphocytes - metabolism ; CD8-Positive T-Lymphocytes - virology ; cell-mediated immunity ; Dengue - immunology ; Dengue - prevention & control ; Dengue Vaccines - immunology ; dengue virus ; Dengue Virus - immunology ; Disease Models, Animal ; Encephalitis, Viral - prevention & control ; Female ; Humans ; Immunization Schedule ; Interferon-gamma - immunology ; Interferon-gamma - metabolism ; Mice ; Mice, Inbred BALB C ; Nucleocapsid - immunology ; Recombinant Proteins - immunology ; virus-like particles</subject><ispartof>International immunology, 2009-10, Vol.21 (10), p.1175-1183</ispartof><rights>The Japanese Society for Immunology. 2009. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c455t-ec0218ae297d7c2e1123eb522268f36a8ef181dbb9ab16b39baf616a6ebe24a23</citedby><cites>FETCH-LOGICAL-c455t-ec0218ae297d7c2e1123eb522268f36a8ef181dbb9ab16b39baf616a6ebe24a23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1578,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19692540$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gil, Lázaro</creatorcontrib><creatorcontrib>López, Carlos</creatorcontrib><creatorcontrib>Lazo, Laura</creatorcontrib><creatorcontrib>Valdés, Iris</creatorcontrib><creatorcontrib>Marcos, Ernesto</creatorcontrib><creatorcontrib>Alonso, Ruby</creatorcontrib><creatorcontrib>Gambe, Ailyn</creatorcontrib><creatorcontrib>Martín, Jorge</creatorcontrib><creatorcontrib>Romero, Yaremis</creatorcontrib><creatorcontrib>Guzmán, María G.</creatorcontrib><creatorcontrib>Guillén, Gerardo</creatorcontrib><creatorcontrib>Hermida, Lisset</creatorcontrib><title>Recombinant nucleocapsid-like particles from dengue-2 virus induce protective CD4+ and CD8+ cells against viral encephalitis in mice</title><title>International immunology</title><addtitle>Int Immunol</addtitle><description>Virus-like particles are a highly effective type of subunit vaccine that mimics the overall structure of virus particles without containing infectious genetic material. In this work, a particulate form of the recombinant capsid protein from dengue-2 was evaluated in mice to determine the level of protection against viral challenge and to measure the antigen-induced cell-mediated immunity (CMI). The nucleocapsid-like particles (NLPs) adjuvanted with alum did not induce antiviral antibodies. However, splenocytes from the immunized animals secreted high levels of IFN-γ upon virus stimulation, and a significant protection rate was achieved after challenge with lethal dengue-2 virus. Finally, both IFN-γ secretion and protection against viral encephalitis were demonstrated to be dependent on CD4+ and CD8+ cells. This study provides new evidences regarding the protective role of the CMI in the mouse model without the induction of neutralizing antibodies. Further studies in non-human primates or humanized mice should be carried out to elucidate the usefulness of the NLPs as a potential vaccine candidate against dengue disease.</description><subject>Animals</subject><subject>Antibodies, Viral - blood</subject><subject>capsid protein</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>CD4-Positive T-Lymphocytes - metabolism</subject><subject>CD4-Positive T-Lymphocytes - virology</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>CD8-Positive T-Lymphocytes - metabolism</subject><subject>CD8-Positive T-Lymphocytes - virology</subject><subject>cell-mediated immunity</subject><subject>Dengue - immunology</subject><subject>Dengue - prevention & control</subject><subject>Dengue Vaccines - immunology</subject><subject>dengue virus</subject><subject>Dengue Virus - immunology</subject><subject>Disease Models, Animal</subject><subject>Encephalitis, Viral - prevention & control</subject><subject>Female</subject><subject>Humans</subject><subject>Immunization Schedule</subject><subject>Interferon-gamma - immunology</subject><subject>Interferon-gamma - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Nucleocapsid - immunology</subject><subject>Recombinant Proteins - immunology</subject><subject>virus-like particles</subject><issn>0953-8178</issn><issn>1460-2377</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkMtv1DAQhy0EotuFI1fkG0hVqB-JH0e0QItUCVEeqnqxbGdSTBMntZ2q3PnDySorOHKa0eib34w-hF5Q8oYSzU9DLGEYTtuHiSj2CG1oLUjFuJSP0YbohleKSnWEjnP-SQjhTPOn6IhqoVlTkw36fQl-HFyINhYcZ9_D6O2UQ1v14RbwZFMJyzDjLo0DbiHezFAxfB_SnHGI7ewXKI0FfAn3gHfv6hNsY7s06gR76PuM7Y0NMZf9ju0xRA_TD9uHEvYBeAgenqEnne0zPD_ULfr24f3X3Xl18ens4-7tReXrpikVeMKossC0bKVnQCnj4BrGmFAdF1ZBRxVtndPWUeG4drYTVFgBDlhtGd-iV2vu8vHdDLmYIeT9kzbCOGcjeU0apRdHW1StpE9jzgk6M6Uw2PTLUGL23s3q3azeF_7lIXl2A7T_6IPoBXi9AuM8_TfrcDvkAg9_YZtujZBcNub86towKa-_X11-MZ_5HwOan6w</recordid><startdate>20091001</startdate><enddate>20091001</enddate><creator>Gil, Lázaro</creator><creator>López, Carlos</creator><creator>Lazo, Laura</creator><creator>Valdés, Iris</creator><creator>Marcos, Ernesto</creator><creator>Alonso, Ruby</creator><creator>Gambe, Ailyn</creator><creator>Martín, Jorge</creator><creator>Romero, Yaremis</creator><creator>Guzmán, María G.</creator><creator>Guillén, Gerardo</creator><creator>Hermida, Lisset</creator><general>Oxford University Press</general><scope>BSCLL</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>7X8</scope></search><sort><creationdate>20091001</creationdate><title>Recombinant nucleocapsid-like particles from dengue-2 virus induce protective CD4+ and CD8+ cells against viral encephalitis in mice</title><author>Gil, Lázaro ; López, Carlos ; Lazo, Laura ; Valdés, Iris ; Marcos, Ernesto ; Alonso, Ruby ; Gambe, Ailyn ; Martín, Jorge ; Romero, Yaremis ; Guzmán, María G. ; Guillén, Gerardo ; Hermida, Lisset</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c455t-ec0218ae297d7c2e1123eb522268f36a8ef181dbb9ab16b39baf616a6ebe24a23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Animals</topic><topic>Antibodies, Viral - blood</topic><topic>capsid protein</topic><topic>CD4-Positive T-Lymphocytes - immunology</topic><topic>CD4-Positive T-Lymphocytes - metabolism</topic><topic>CD4-Positive T-Lymphocytes - virology</topic><topic>CD8-Positive T-Lymphocytes - immunology</topic><topic>CD8-Positive T-Lymphocytes - metabolism</topic><topic>CD8-Positive T-Lymphocytes - virology</topic><topic>cell-mediated immunity</topic><topic>Dengue - immunology</topic><topic>Dengue - prevention & control</topic><topic>Dengue Vaccines - immunology</topic><topic>dengue virus</topic><topic>Dengue Virus - immunology</topic><topic>Disease Models, Animal</topic><topic>Encephalitis, Viral - prevention & control</topic><topic>Female</topic><topic>Humans</topic><topic>Immunization Schedule</topic><topic>Interferon-gamma - immunology</topic><topic>Interferon-gamma - metabolism</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Nucleocapsid - immunology</topic><topic>Recombinant Proteins - immunology</topic><topic>virus-like particles</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gil, Lázaro</creatorcontrib><creatorcontrib>López, Carlos</creatorcontrib><creatorcontrib>Lazo, Laura</creatorcontrib><creatorcontrib>Valdés, Iris</creatorcontrib><creatorcontrib>Marcos, Ernesto</creatorcontrib><creatorcontrib>Alonso, Ruby</creatorcontrib><creatorcontrib>Gambe, Ailyn</creatorcontrib><creatorcontrib>Martín, Jorge</creatorcontrib><creatorcontrib>Romero, Yaremis</creatorcontrib><creatorcontrib>Guzmán, María G.</creatorcontrib><creatorcontrib>Guillén, Gerardo</creatorcontrib><creatorcontrib>Hermida, Lisset</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>International immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gil, Lázaro</au><au>López, Carlos</au><au>Lazo, Laura</au><au>Valdés, Iris</au><au>Marcos, Ernesto</au><au>Alonso, Ruby</au><au>Gambe, Ailyn</au><au>Martín, Jorge</au><au>Romero, Yaremis</au><au>Guzmán, María G.</au><au>Guillén, Gerardo</au><au>Hermida, Lisset</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Recombinant nucleocapsid-like particles from dengue-2 virus induce protective CD4+ and CD8+ cells against viral encephalitis in mice</atitle><jtitle>International immunology</jtitle><addtitle>Int Immunol</addtitle><date>2009-10-01</date><risdate>2009</risdate><volume>21</volume><issue>10</issue><spage>1175</spage><epage>1183</epage><pages>1175-1183</pages><issn>0953-8178</issn><eissn>1460-2377</eissn><abstract>Virus-like particles are a highly effective type of subunit vaccine that mimics the overall structure of virus particles without containing infectious genetic material. In this work, a particulate form of the recombinant capsid protein from dengue-2 was evaluated in mice to determine the level of protection against viral challenge and to measure the antigen-induced cell-mediated immunity (CMI). The nucleocapsid-like particles (NLPs) adjuvanted with alum did not induce antiviral antibodies. However, splenocytes from the immunized animals secreted high levels of IFN-γ upon virus stimulation, and a significant protection rate was achieved after challenge with lethal dengue-2 virus. Finally, both IFN-γ secretion and protection against viral encephalitis were demonstrated to be dependent on CD4+ and CD8+ cells. This study provides new evidences regarding the protective role of the CMI in the mouse model without the induction of neutralizing antibodies. Further studies in non-human primates or humanized mice should be carried out to elucidate the usefulness of the NLPs as a potential vaccine candidate against dengue disease.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>19692540</pmid><doi>10.1093/intimm/dxp082</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0953-8178 |
| ispartof | International immunology, 2009-10, Vol.21 (10), p.1175-1183 |
| issn | 0953-8178 1460-2377 |
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| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Animals Antibodies, Viral - blood capsid protein CD4-Positive T-Lymphocytes - immunology CD4-Positive T-Lymphocytes - metabolism CD4-Positive T-Lymphocytes - virology CD8-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - metabolism CD8-Positive T-Lymphocytes - virology cell-mediated immunity Dengue - immunology Dengue - prevention & control Dengue Vaccines - immunology dengue virus Dengue Virus - immunology Disease Models, Animal Encephalitis, Viral - prevention & control Female Humans Immunization Schedule Interferon-gamma - immunology Interferon-gamma - metabolism Mice Mice, Inbred BALB C Nucleocapsid - immunology Recombinant Proteins - immunology virus-like particles |
| title | Recombinant nucleocapsid-like particles from dengue-2 virus induce protective CD4+ and CD8+ cells against viral encephalitis in mice |
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