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A human immune data-informed vaccine concept elicits strong and broad T-cell specificities associated with HIV-1 control in mice and macaques

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dc.contributor Universitat de Vic - Universitat Central de Catalunya. Càtedra de la Sida i Malalties Relacionades
dc.contributor.author Mothe, B.
dc.contributor.author Hu, Xintao
dc.contributor.author Llano, Anuska
dc.contributor.author Rosati, Margherita
dc.contributor.author Olvera, Alex
dc.contributor.author Kulkarni, Viraj
dc.contributor.author Valentin, Antonio
dc.contributor.author Alicea, Candido
dc.contributor.author Pilkington, Guy R.
dc.contributor.author Sardesai, Niranjan J.
dc.contributor.author Rocafort, Muntsa
dc.contributor.author Crespo, Manel
dc.contributor.author Carrillo, Jorge
dc.contributor.author Marco, Andrés
dc.contributor.author Mullins, James I.
dc.contributor.author Dorrell, Lucy
dc.contributor.author Hanke, Thomas
dc.contributor.author Clotet, Bonaventura
dc.contributor.author Pavlakis, George N.
dc.contributor.author Felber, Barbara
dc.contributor.author Brander, Christian
dc.date.accessioned 2015-04-16T10:22:23Z
dc.date.available 2015-04-16T10:22:23Z
dc.date.created 2015
dc.date.issued 2015
dc.identifier.citation Mothe, B., Hu, X., Llano, A., Rosati, M., Olvera, A., Kulkarni, V., et al. (2015). A human immune data-informed vaccine concept elicits strong and broad T-cell specificities associated with HIV-1 control in mice and macaques BioMed Central Ltd.13 (1) art. No 60 ca_ES
dc.identifier.issn 1479-5876
dc.identifier.uri http://hdl.handle.net/10854/3992
dc.description.abstract Background: None of the HIV T-cell vaccine candidates that have reached advanced clinical testing have been able to induce protective T cell immunity. A major reason for these failures may have been suboptimal T cell immunogen designs. Methods: To overcome this problem, we used a novel immunogen design approach that is based on functional T cell response data from more than 1,000 HIV-1 clade B and C infected individuals and which aims to direct the T cell response to the most vulnerable sites of HIV-1. Results: Our approach identified 16 regions in Gag, Pol, Vif and Nef that were relatively conserved and predominantly targeted by individuals with reduced viral loads. These regions formed the basis of the HIVACAT T-cell Immunogen (HTI) sequence which is 529 amino acids in length, includes more than 50 optimally defined CD4+ and CD8+ T-cell epitopes restricted by a wide range of HLA class I and II molecules and covers viral sites where mutations led to a dramatic reduction in viral replicative fitness. In both, C57BL/6 mice and Indian rhesus macaques immunized with an HTI-expressing DNA plasmid (DNA.HTI) induced broad and balanced T-cell responses to several segments within Gag, Pol, and Vif. DNA.HTI induced robust CD4+ and CD8+ T cell responses that were increased by a booster vaccination using modified virus Ankara (MVA.HTI), expanding the DNA.HTI induced response to up to 3.2% IFN-γ T-cells in macaques. HTI-specific T cells showed a central and effector memory phenotype with a significant fraction of the IFN-γ+ CD8+ T cells being Granzyme B+ and able to degranulate (CD107a+). Conclusions: These data demonstrate the immunogenicity of a novel HIV-1 T cell vaccine concept that induced broadly balanced responses to vulnerable sites of HIV-1 while avoiding the induction of responses to potential decoy targets that may divert effective T-cell responses towards variable and less protective viral determinants. ca_ES
dc.format application/pdf
dc.format.extent 23 p. ca_ES
dc.language.iso eng ca_ES
dc.publisher BioMed Central ca_ES
dc.rights Aquest document està subjecte a aquesta llicència Creative Commons ca_ES
dc.rights.uri http://creativecommons.org/licenses/by/3.0/es/ ca_ES
dc.subject.other VIH (Virus) ca_ES
dc.subject.other Antígens HLA ca_ES
dc.subject.other Immunogenètica ca_ES
dc.subject.other Sida -- Tractament
dc.title A human immune data-informed vaccine concept elicits strong and broad T-cell specificities associated with HIV-1 control in mice and macaques ca_ES
dc.type info:eu-repo/semantics/article ca_ES
dc.identifier.doi https://doi.org/10.1186/s12967-015-0392-5
dc.rights.accesRights info:eu-repo/semantics/openAccess ca_ES
dc.type.version info:eu-repo/publishedVersion ca_ES
dc.indexacio Indexat a SCOPUS ca_ES

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