MHC class I associated peptides for prevention and treatment of hepatitis B virus infection
Inventors
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-10155036-B2
Publication Date
2018-12-18
Expiration Date
Abstract
The present invention relates to compositions and methods for the prevention, treatment, and diagnosis of Hepatitis B virus (HBV) infection, and discloses peptides, polypeptides, and polynucleotides that can be used to stimulate a CTL response against HBV infection. The peptide and/or proteins of the invention may be used as a therapeutic drug to stimulate the immune system to recognize and eliminate HBV infection in infected cells or as a vaccine for the prevention of disease.
Core Innovation
The described invention relates to hepatitis B virus (HBV) immunogens based on MHC class I-associated epitopic peptides that are naturally presented by chronically HBV-infected cells and are associated with HLA-A2 and HLA-A24 supertypes. The immunogens comprise peptide, protein, and polynucleotide immunogens configured to engage class I MHC presentation and a T lymphocyte response, including epitopes such as SEQ ID NO: 1-17.
A peptide immunogen is described as consisting of 8 to about 30 amino acid residues and comprising an amino acid sequence such as SEQ ID NO: 2, with binding to class I MHC molecules from A2 and A24 supertypes, or the ability to be processed to bind to those class I MHC molecules. Closely related peptide sequences differ by no more than one amino acid from the referenced sequence via a conservative amino acid substitution.
The disclosure provides experimental support using immunoproteomics to identify MHC class I peptides presented in the context of HBV, followed by characterization of HLA-A2/A24-restricted CTL activation for selected peptides. The CTL functional readouts described include IFN-gamma ELISpot, CD107a degranulation marker, and granzyme B secretion, and the disclosure links the identified epitopic peptides to induction and functional assessment of antigen-specific CTL responses in vitro and in vivo.
Claims Coverage
The partial claim set includes three independent claims. The main inventive features are the specified 8 to about 30 amino acid peptide SEQ ID NO: 2 and closely related conservative variants, the ability to bind or be processed to bind class I MHC molecules from A2 and A24 supertypes, activation of a T lymphocyte response, and use as a pharmaceutically acceptable salt in pharmaceutical composition and method claims.
Pharmaceutical composition with A2/A24 supertypes class I MHC-binding peptide immunogen
A pharmaceutical composition comprising at least one peptide consisting of 8 to about 30 amino acid residues and comprising the amino acid sequence of SEQ ID NO: 2, wherein said peptide can bind to class I MHC molecules from A2 and A24 supertypes, or can be processed to bind to class I MHC molecules from A2 and A24 supertypes, and activate a T lymphocyte response, and wherein the peptide is in the form of a pharmaceutically acceptable salt.
Vaccinating and treating HBV infection by inducing CTL responses with SEQ ID NO: 2 peptide composition
A method for vaccinating and treating a subject for HBV infection, comprising administering a pharmaceutical composition in an amount sufficient to induce a CTL response to infected cells expressing any class I MHC molecule, wherein the composition comprises at least one peptide consisting of 8 to about 30 amino acid residues and comprising the amino acid sequence of SEQ ID NO: 2, or a conservative one-amino-acid variant, and wherein the peptide can bind to class I MHC molecules from A2 and A24 supertypes, or can be processed to bind to such molecules, and activate a T lymphocyte response, in the form of a pharmaceutically acceptable salt.
Vaccinating humans against HBV using SEQ ID NO: 2 peptide composition
A method for vaccinating humans against HBV infection using a pharmaceutical composition comprising at least one peptide consisting of 8 to about 30 amino acid residues and comprising the amino acid sequence of SEQ ID NO: 2, or a conservative one-amino-acid variant, wherein said peptide can bind to class I MHC molecules from A2 and A24 supertypes, or can be processed to bind to such molecules, and activate a T lymphocyte response, and wherein the peptide is in the form of a pharmaceutically acceptable salt.
The independent claims collectively emphasize a pharmaceutical composition and related vaccination or treatment methods using an 8 to about 30 amino acid peptide immunogen defined by SEQ ID NO: 2 or a conservative one-amino-acid variant. The peptide is characterized by binding, or being processed to bind, class I MHC molecules from A2 and A24 supertypes to activate a T lymphocyte response, with the method claims further directed to inducing CTL responses against HBV-infected cells and vaccinating humans against HBV infection.
Stated Advantages
Induces a CTL response to HBV-infected cells expressing class I MHC molecules.
Activates a T lymphocyte response via peptides that can bind to or be processed to bind class I MHC molecules from A2 and A24 supertypes.
Supports prevention and treatment of HBV infection through vaccination and treatment of a subject for HBV infection.
Documented Applications
Vaccinating and treating a subject for HBV infection by administering a pharmaceutical composition to induce a CTL response to HBV-infected cells expressing class I MHC.
Vaccinating humans against HBV infection using a pharmaceutical composition containing the specified class I MHC-associated peptide immunogen.
Optional diagnosis is described as an application based on the peptide immunogens and CTL response context.
Interested in licensing this patent?