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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：US09862972B2
公开(公告)日：2018-01-09
申请号：US14086602
申请日：2013-11-21
发明人： Louis Picker , Klaus Früh , Scott Hansen
CPC分类号： C12N15/86 , A61K39/12 , A61K2039/5256 , C12N7/00 , C12N2710/16121 , C12N2710/16143 , C12N2740/15034 , C12N2740/15071 , C12N2800/204 , Y02A50/386 , Y02A50/388 , Y02A50/394 , Y02A50/412 , Y02A50/466
摘要： Disclosed herein are recombinant CMV vectors which may comprise a heterologous antigen that can repeatedly infect an organism while inducing a CD8+ T cell response to immunodominant epitopes of the heterologous antigen. The CMV vector may comprise a deleterious mutation in the US11 glycoprotein or a homolog thereof.
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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：US20180087069A1
公开(公告)日：2018-03-29
申请号：US15693558
申请日：2017-09-01
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.A clean version of the amended Abstract is provided below: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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5.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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7.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：US20170143809A1
公开(公告)日：2017-05-25
申请号：US15356627
申请日：2016-11-20
发明人： Jay Nelson , Scott Hansen , Meaghan H. Hancock , Louis Picker , Klaus Frueh
IPC分类号： A61K39/00
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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10.发明授权公开(公告)号：US11305015B2
公开(公告)日：2022-04-19
申请号：US16696403
申请日：2019-11-26
发明人： Louis Picker , Scott Hansen , Klaus Frueh , Daniel Malouli , Jay Nelson , Jonah Sacha , Meaghan Hancock
IPC分类号： A61K45/00 , A61K39/00 , A61K39/12 , C12N7/04 , C12N15/86 , C12N15/113 , A61P31/14 , C07K14/005
摘要： 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 are provided. Immunization with CMV vectors having the described features allows selection of different CD8+ T cell responses—CD8+ T cells restricted by MHC-Ia, MHC-II, or by MHC-E.
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