CMV glycoproteins and recombinant vectors
AssigneeOregon Health & Science University
InventorsLouis Picker, Klaus Früh, Scott Hansen
Life of this patent
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Abstract
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.
Claims55
A method of eliciting an immune response to at least one immunodominant epitope of at least one heterologous antigen in a cytomegalovirus (CMV)-seropositive subject in need thereof, the method comprising administering a recombinant CMV vector encoding the at least one heterologous antigen to the CMV-seropositive subject in an amount effective to elicit a long-term CD8+ T cell response to the at least one immunodominant epitope,
- wherein the recombinant CMV vector does not express an active US11 protein or a functional homologue thereof, and
- wherein the recombinant CMV vector encodes functional US2, US3, and US6 proteins, or functional homologues thereof.
A method of eliciting an immune response to at least one immunodominant epitope of at least one heterologous antigen in a CMV-seropositive subject in need thereof, the method comprising administering a recombinant CMV vector to the CMV-seropositive subject in an amount effective to elicit a long-term CD8+ T cell response to the at least one immunodominant epitope;
- wherein the recombinant CMV vector does not express an active US11 protein or a functional homologue thereof;
- wherein the recombinant CMV vector comprises:
- a nucleic acid sequence encoding functional US2, US3, and US6 proteins, or functional homologues thereof;
- a nucleic acid sequence encoding US12 or a functional homologue thereof;
- and a nucleic acid sequence encoding the at least one heterologous antigen;
- and
- wherein the nucleic acid sequence encoding the at least one heterologous antigen is located between the nucleic acid sequence encoding US6 or a functional homologue thereof and the nucleic acid sequence encoding US12 or a functional homologue thereof.
A method of eliciting an immune response to at least one immunodominant epitope of at least one heterologous antigen in a HCMV-seropositive subject in need thereof, the method comprising administering a recombinant HCMV vector to the HCMV-seropositive subject in an amount effective to elicit a long-term CD8+ T cell response to the at least one immunodominant epitope;
- wherein the recombinant HCMV vector does not express an active US11 protein or a functional homologue thereof;
- wherein the recombinant HCMV vector comprises:
- a nucleic acid sequence encoding functional US2, US3, and US6 proteins;
- a nucleic acid sequence encoding US12;
- and a nucleic acid sequence encoding the at least one heterologous antigen;
- and
- wherein the nucleic acid sequence encoding the at least one heterologous antigen is located between the nucleic acid sequence encoding US6 and the nucleic acid sequence encoding US12.
A method of eliciting an immune response to at least one immunodominant epitope of at least one heterologous antigen in a HCMV-seropositive subject in need thereof, the method comprising administering a recombinant HCMV vector encoding the at least one heterologous antigen to the HCMV-seropositive subject in an amount effective to elicit a long-term CD8+ T cell response to the at least one immunodominant epitope,
- wherein the at least one heterologous antigen is a herpes simplex virus (HSV) antigen or a human papillomavirus antigen,
- wherein the recombinant HCMV vector does not express an active US11 protein, and
- wherein the recombinant HCMV vector encodes functional US2, US3, and US6 proteins.
Dependencies are inferred from the claim text.