DNA-peptide combination vaccine
Inventors
Nakagami, Hironori • Morishita, Ryuichi • Koriyama, Hiroshi • Tomioka, Hideki • NAOHARA, Kenji
Assignees
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Publication Number
US-10695420-B2
Publication Date
2020-06-30
Expiration Date
Abstract
The present invention provides a combination preparation for inducing a specific immune response to an antigenic peptide, which contains (I) the antigenic peptide, and(II) an expression vector encoding a chimeric hepatitis B virus core antigen polypeptide, into which the antigenic peptide has been inserted or added, wherein said antigenic peptide is inserted in a region of amino acid residues 74-87 or 130-138 of the hepatitis B virus core antigen polypeptide, or added to the N-terminal or C-terminal of the hepatitis B virus core antigen polypeptide, whereinthe antigenic peptide of (I) and the expression vector of (II) are substantially simultaneously administered to a subject.
Core Innovation
The invention relates to a DNA-peptide combination vaccine for inducing a specific immune response to an angiotensin II peptide in a subject. The combination includes an angiotensin II peptide consisting of the amino acid sequence of DRVYIHPF (SEQ ID NO: 21) and an expression vector encoding a chimeric hepatitis B virus core antigen polypeptide.
The angiotensin II peptide is inserted in a region of amino acid residues 74-87 or 130-138 of the hepatitis B virus core antigen polypeptide, or is added to the N-terminal or C-terminal of the hepatitis B virus core antigen polypeptide. The angiotensin II peptide is cross-linked with a carrier protein, and the angiotensin II peptide and the expression vector are substantially simultaneously administered to the subject.
The document emphasizes inducing strong, long-lasting peptide-specific antibodies. The described carrier protein cross-linking and the chimeric hepatitis B virus core antigen self-assembly and surface presentation are used as the basis for the immune response.
Claims Coverage
The document provides two independent claims and several dependents that refine peptide insertion positions, carrier protein, formulation as a single preparation, exclusion of adjuvants, administration route, and additional administration facilitation tools. Across both independent claims, the inventive features jointly define co-formulated co-administration of DRVYIHPF with a chimeric HBc expression vector, peptide insertion/attachment in specified HBc regions, peptide cross-linking with a carrier protein, and substantially simultaneous administration.
Angiotensin II peptide DRVYIHPF with chimeric hepatitis B virus core antigen expression vector
The combination for inducing a specific immune response to an angiotensin II peptide comprises an angiotensin II peptide consisting of the amino acid sequence of DRVYIHPF (SEQ ID NO: 21) and an expression vector encoding a chimeric hepatitis B virus core antigen polypeptide, into which the angiotensin II peptide has been inserted or added.
Specified insertion or N/C-terminal addition in hepatitis B virus core antigen
The angiotensin II peptide is inserted in a region of amino acid residues 74-87 or 130-138 of the hepatitis B virus core antigen polypeptide, or added to the N-terminal or C-terminal of the hepatitis B virus core antigen polypeptide.
Cross-linking with a carrier protein
The angiotensin II peptide is cross-linked with a carrier protein.
Substantially simultaneous administration of peptide and expression vector
The angiotensin II peptide and the expression vector are substantially simultaneously administered to the subject.
Substantially simultaneous peptide and expression vector administration method
The method comprises substantially simultaneously administering to the subject one or more times the angiotensin II peptide consisting of the amino acid sequence of DRVYIHPF (SEQ ID NO: 21) and an expression vector encoding a chimeric hepatitis B virus core antigen polypeptide, into which the angiotensin II peptide has been inserted or added.
Specified insertion or N/C-terminal addition in method
The angiotensin II peptide is inserted in a region of amino acid residues 74-87 or 130-138 of the hepatitis B virus core antigen polypeptide, or added to the N-terminal or C-terminal of the hepatitis B virus core antigen polypeptide.
Cross-linking with a carrier protein in the method
The angiotensin II peptide is cross-linked with a carrier protein.
Claim coverage is centered on a co-delivery immune approach in which DRVYIHPF (SEQ ID NO: 21) is inserted into or attached to a chimeric hepatitis B virus core antigen polypeptide in specified HBc regions or at the N-terminal/C-terminal, is cross-linked with a carrier protein, and is administered substantially simultaneously with the HBc expression vector to induce a specific immune response.
Stated Advantages
Induce strong, long-lasting peptide-specific antibodies.
Documented Applications
Treating or preventing cardiovascular and related diseases including cardiac failure (including mitral insufficiency).
Angiotensin II peptide-directed immune response for hypertension.
Angiotensin II peptide-directed immune response for renal failure.
Angiotensin II peptide-directed immune response for arteriosclerosis/atherosclerosis and myocardial infarction.
Angiotensin II peptide-directed immune response for cerebral infarction.
Angiotensin II peptide-directed immune response for dementia.
Examples report blood pressure reduction and improvement of cardiac failure parameter.
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