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公开(公告)号：US11091779B2
公开(公告)日：2021-08-17
申请号：US16738178
申请日：2020-01-09
发明人： Klaus Frueh , Louis Picker , Scott Hansen , Jonah Sacha , Daniel Malouli
IPC分类号： C12N15/86 , C12N9/02 , C12Q1/68 , C12N15/00 , A61K39/12 , A61K35/17 , A61K39/21 , A61K39/245 , C12N7/00 , A61K39/00
摘要： Methods of inducing a CD8+ T cell response to a heterologons antigen in which at least 10% of the CD8+ T cells are MHC-E restricted are disclosed. The method involves immunizing with a CMV vector that does not express UL128 and UL130 proteins. Also disclosed are recombinant CMV vectors comprising nucleic acids encoding a heterologous protein antigen, a UL40 protein, and a US28 protein but that do not express an active UL128 and UL130 protein. Also, disclosed are recombinant CMV vectors comprising nucleic acids encoding a heterologous protein antigen, but that do not express an active UL40 protein, UL128 protein, UL130 protein, and optionally a US28 protein. Also disclosed are recombinant CMV vectors comprising nucleic acids encoding a heterologous protein antigen, but that do not express an active US28 protein, UL128 protein, UL130 protein, and optionally a UL40 protein.
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公开(公告)号：US20210046175A1
公开(公告)日：2021-02-18
申请号：US17008335
申请日：2020-08-31
发明人： Eric Bruening , Klaus Frueh , Louis Picker , Bette T.M. Korber , James Theiler , Emily Marshall
摘要： Provided herein are HIV-1 vaccines comprising a carrier and a population episensus antigen determined using the EpiGraph approach. Also provided are HIV-1 vaccines comprising a carrier, a population episensus antigen, and a tailored antigen. Also provided are methods of designing and producing an HIV-1 vaccine for a subject comprising designing vaccine antigens to optimally cover the diversity within a geographic area using an antigen amino acid sequence generated using the EpiGraph approach, and producing said designed vaccine antigen. Also provided are methods of inducing an effector memory T cell response comprising designing the one or more EpiGraph amino acid sequences, producing a vaccine comprising the one or more EpiGraph amino acid sequences and a vector, and administering the vaccine to a subject. Further provided are methods of treating HIV-1 in a subject comprising administering an effective amount of the described HIV-1 vaccines to the subject in need thereof.
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公开(公告)号：US20210046174A1
公开(公告)日：2021-02-18
申请号：US17008289
申请日：2020-08-31
发明人： Eric Bruening , Klaus Frueh , Louis Picker , Bette T.M. Korber , James Theiler , Emily Marshall
摘要： Provided herein are HIV-1 vaccines comprising a carrier and a population episensus antigen determined using the EpiGraph approach. Also provided are HIV-1 vaccines comprising a carrier, a population episensus antigen, and a tailored antigen. Also provided are methods of designing and producing an HIV-1 vaccine for a subject comprising designing vaccine antigens to optimally cover the diversity within a geographic area using an antigen amino acid sequence generated using the EpiGraph approach, and producing said designed vaccine antigen. Also provided are methods of inducing an effector memory T cell response comprising designing the one or more EpiGraph amino acid sequences, producing a vaccine comprising the one or more EpiGraph amino acid sequences and a vector, and administering the vaccine to a subject. Further provided are methods of treating HIV-1 in a subject comprising administering an effective amount of the described HIV-1 vaccines to the subject in need thereof.
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4.发明授权公开(公告)号：US10532099B2
公开(公告)日：2020-01-14
申请号：US15786847
申请日：2017-10-18
发明人： Louis Picker , Scott Hansen , Klaus Frueh , Daniel Malouli , Jay Nelson , Jonah Sacha , Meaghan Hancock
摘要： Disclosed are CMV vectors that lack active UL128, UL130, UL146 and UL147 proteins that may also comprise one or more microRNA regulatory elements (MRE) that restrict expression of the CMV. Immunization with the disclosed CMV vectors allow selection of different CD8+ T cell responses—CD8+ T cells restricted by MHC-Ia, MHC-II, or by MHC-E.
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公开(公告)号：US10316334B2
公开(公告)日：2019-06-11
申请号：US15693558
申请日：2017-09-01
发明人： Louis Picker , Scott Hansen , Klaus Frueh , Daniel Malouli
摘要： CMV vectors comprising a heterologous protein antigen, an active UL131 protein (or an ortholog thereof), and an active UL128 protein (or an ortholog thereof) but lacking an active UL130 protein (or an ortholog thereof) are provided. CMV vectors comprising a heterologous protein antigen, an active UL131 protein (or an ortholog thereof), and an active UL130 protein (or an ortholog thereof) but lacking an active UL128 protein are also provided. In addition, methods of using CMV vectors to generate an immune response characterized as having at least 10% of the CD8+ T cells directed against epitopes presented by MHC Class II are provided.
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6.发明申请公开(公告)号：US20180133321A1
公开(公告)日：2018-05-17
申请号：US15786847
申请日：2017-10-18
发明人： Louis Picker , Scott Hansen , Klaus Frueh , Daniel Malouli , Jay Nelson , Jonah Sacha , Meaghan Hancock
摘要： Disclosed are CMV vectors that lack active UL128, UL130, UL146 and UL147 proteins that may also comprise one or more microRNA regulatory elements (MRE) that restrict expression of the CMV. Immunization with the disclosed CMV vectors allow selection of different CD8+ T cell responses—CD8+ T cells restricted by MHC-Ia, MHC-II, or by MHC-E.
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公开(公告)号：US09783823B2
公开(公告)日：2017-10-10
申请号：US14773130
申请日：2014-03-05
发明人： Louis Picker , Scott Hansen , Klaus Frueh , Daniel Malouli
CPC分类号： C12N15/86 , A61K39/04 , A61K39/12 , A61K39/21 , A61K48/00 , A61K2039/5256 , A61K2039/572 , C12N7/00 , C12N2710/16011 , C12N2710/16143 , C12N2740/15034
摘要： CMV vectors comprising a heterologous protein antigen, an active UL131 protein (or an ortholog thereof), and an active UL128 protein (or an ortholog thereof) but lacking an active UL130 protein (or an ortholog thereof) are provided. CMV vectors comprising a heterologous protein antigen, an active UL131 protein (or an ortholog thereof), and an active UL130 protein (or an ortholog thereof) but lacking an active UL128 protein are also provided. In addition, methods of using CMV vectors to generate an immune response characterized as having at least 10% of the CD8+ T cells directed against epitopes presented by MHC Class II are provided.
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公开(公告)号：US10688164B2
公开(公告)日：2020-06-23
申请号：US15356627
申请日：2016-11-20
发明人： Jay Nelson , Scott Hansen , Meaghan H. Hancock , Louis Picker , Klaus Frueh
摘要： Disclosed herein are recombinant CMV vectors comprising heterologous antigens and microRNA recognition elements to silence expression of CMV genes in the presence of microRNA derived from myeloid cells, an active UL128 protein and an active UL130 protein. Also disclosed are recombinant CMV vectors comprising heterologous antigens and microRNA recognition elements to silence expression of CMV genes in the presence of microRNA derived from myeloid cells, an inactive UL128 protein and an inactive UL130 protein. Also disclosed are methods of generating an unconventional immune response using these vectors. Such an immune response is characterized by generation of a CD8+ T cell response that is predominantly restricted by MHC-II.
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公开(公告)号：US10428118B2
公开(公告)日：2019-10-01
申请号：US15326444
申请日：2015-07-16
发明人： Klaus Frueh , Scott G. Hansen , Jay Nelson , Louis Picker , Patrizia Caposio
IPC分类号： C07K14/045 , C12N15/86 , A61K39/12 , A61K35/33 , A61K39/00 , A61K39/39 , C12N15/85 , A61K39/21 , C07K14/16 , A61P35/00
摘要： Human cytomegalovirus vectors comprising heterologous antigens are disclosed. The vectors derived from the TR strain, are ganciclovir-sensitive, include active US2, US3, US6, US7 and UL131A genes, and have a deleterious or inactivating mutation in the UL82 gene preventing the expression of pp71.
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公开(公告)号：US10101329B2
公开(公告)日：2018-10-16
申请号：US15374938
申请日：2016-12-09
发明人： Louis Picker , Klaus Frueh , Scott G. Hansen , Colin Powers
IPC分类号： G01N33/569 , A61K39/00 , A61K39/12 , A61K39/21 , C12N7/00 , A61K39/245 , A61K39/02
摘要： This invention also relates to recombinant vectors expressing one or more of the human CMV (HCMV) glycoproteins US2, US3, US6 and US11 or corresponding functional rhesus CMV (RhCMV) homologues Rh182, Rh184, Rh185 or Rh189, methods of making them, uses for them, expression products from them, and uses for the expression products. This invention also relates to recombinant cytomegalovirus vectors vectors lacking one or more of the glycoproteins, methods of making them, uses for them, expression products from them, and uses for the expression products.
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