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US 10,532,099 B2Granted
Cytomegalovirus vectors eliciting T cells restricted by major histocompatibility complex E molecules
AssigneeOregon Health & Science University
InventorsLouis Picker, Scott Hansen, Klaus Frueh, Daniel Malouli, Jay Nelson, Jonah Sacha, Meaghan Hancock
Life of this patent
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Abstract
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.
Claims67
A cytomegalovirus (CMV) vector comprising:
- (a) a first nucleic acid sequence that encodes at least one heterologous antigen;
- and
- (b) a second nucleic acid sequence comprising a first heterologous microRNA recognition element (MRE) operably linked to a CMV gene that is essential or augmenting for CMV growth, wherein the MRE is complementary to a microRNA that is expressed by a cell of endothelial lineage;
- wherein the vector does not express an active UL128 protein or ortholog thereof;
- does not express an active UL130 protein or ortholog thereof;
- does not express an active UL146 or ortholog thereof;
- and does not express an active UL147 protein or ortholog thereof;
- and wherein the microRNA is miR-126-3p, miR-130a, miR-210, miR-221/222, miR-378, miR-296, or miR-328.
5 more elements
A cytomegalovirus (CMV) vector comprising:
- (a) a first nucleic acid sequence that encodes at least one heterologous antigen;
- (b) a second nucleic acid sequence comprising a first heterologous microRNA recognition element (MRE) operably linked to a CMV gene that is essential or augmenting for CMV growth, wherein the MRE is complementary to a first microRNA that is expressed by a cell of endothelial lineage;
- and
- (c) a third nucleic acid sequence comprising a second heterologous MRE operably linked to a CMV gene that is essential or augmenting for CMV growth, wherein the second MRE is complementary to a second microRNA that is expressed by a cell of myeloid lineage;
- wherein the vector does not express an active UL128 protein or ortholog thereof;
- does not express an active UL130 protein or ortholog thereof;
- does not express an active UL146 protein or ortholog thereof;
- and does not express an active UL147 protein or ortholog thereof;
- wherein the first microRNA is miR-126-3p, miR-130a, miR-210, miR-221/222, miR-378, miR-296, or miR-328:
- and wherein the second microRNA is miR-142-3p, miR-223, miR-27a, miR-652, miR-155, miR-146a, miR-132, miR-21, or miR-125.
7 more elements
Dependencies are inferred from the claim text.