# US 8,394,386 B2 · Sequential delivery of immunogenic molecules via adenovirus and adeno-associated virus-mediated administrations > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 8,394,386 B2 - Document ID: US8394386B2 - Status: Granted - Kind: B2 - Application number: 11/587,543 - Filed: 2005-04-27 - Published: 2008-10-02 - Granted: 2013-03-12 - Earliest claimed: 2004-04-28 - Assignees: The Trustees of the University of Pennsylvania - Applicants: James M. Wilson - Inventors: James M. Wilson - Web page: https://patentgrep.com/patent/US8394386B2 ## CPC - C12N 15/86: Viral vectors - A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics - A61P 37/00: Drugs for immunological or allergic disorders - A61K 2039/5256: {expressing foreign proteins} - A61K 2039/545: {characterised by the dose, timing or administration schedule} - C12N 2710/10322: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes - C12N 2710/10343: viral genome or elements thereof as genetic vector - C12N 2750/14143: viral genome or elements thereof as genetic vector - C12N 2760/14122: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes - C12N 2760/14134: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein - C12N 2830/002: inducible enhancer/promoter combination, e.g. hypoxia, iron, transcription factor - C12N 2830/55: from bacteria - Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE ## Abstract An immunogenic regimen is provided. The regimen involves sequential administration of a recombinant adenoviral vector and a recombinant adeno-associated viral vector, each of which delivers a heterologous expression cassette encoding the same immunogenic product, or a cross-reactive immunogenic product. Also provided are products containing the vectors for use in the regimen of the invention. ## Claims ### Claim 1 An immunization regimen comprising delivering to a subject: (a) a replication-defective adenovirus comprising a first heterologous expression cassette comprising a nucleic acid sequence encoding a product for inducing an immune response to said product under the control of regulatory control sequences which direct expression of said product; and (b) an adeno-associated virus (AAV) comprising a second heterologous expression cassette comprising a nucleic acid sequence encoding said product for inducing an immune response to said product under the control of regulatory control sequences which direct expression of said product, wherein the AAV is delivered prior to delivery of the replication-defective adenovirus. ### Claim 2 (depends on 1) The regimen according to claim 1, wherein the regulatory sequences in the first and second expression cassettes of the replication-defective adenovirus and adeno-associated virus differ. ### Claim 3 (depends on 1) The regimen according to claim 1, wherein the regulatory sequences of the adeno-associated virus comprise an inducible promoter. ### Claim 4 (depends on 3) The regimen according to claim 3, further comprising delivering an inducing agent to the subject following administration of the AAV. ### Claim 5 (depends on 4) The regimen according to claim 4, wherein the inducing agent is administered to the subject following administration of the adenovirus. ### Claim 6 (depends on 1) The regimen according to claim 1, wherein the adenovirus further comprises a deletion in the region selected from the group of adenovirus regions consisting of E2, E3, E4, L1, L2, L3, L4, and L5 region. ### Claim 7 (depends on 1) The regimen according to claim 1, wherein the expression cassette of the adenovirus is located in site of an E1 region. ### Claim 8 (depends on 1) The regimen according to claim 1, wherein the first expression cassette of the adenovirus and/or the second expression cassette of the adeno-associated virus is located in an deleted E3 region. ### Claim 9 (depends on 1) The regimen according to claim 1, wherein the adenovirus is of a serotype selected from the group consisting of C5, C6, C7, C68 and C1. ### Claim 10 (depends on 1) The regimen according to claim 1, wherein the adenovirus is administered orally, intranasally, or intramuscularly. ### Claim 11 (depends on 1) The regimen according to claim 1, wherein the AAV is of a serotype selected from the group consisting of AAV1 and AAV8. ### Claim 12 (depends on 1) The regimen according to claim 1, wherein the AAV is administered intramuscularly. ### Claim 13 (depends on 1) The regimen according to claim 1, wherein the regimen further comprises administering a DNA vaccine. ### Claim 14 (depends on 13) The regimen according to claim 13, wherein said DNA vaccine is administered prior to the AAV vector. ### Claim 15 (depends on 1) The regimen according to claim 1, further comprising administering a protein-based vaccine. ### Claim 16 (depends on 15) The regimen according to claim 15, wherein said protein-based vaccine is delivered after the adenoviral vector. ### Claim 17 (depends on 15) The regimen according to claim 15, wherein said protein-based vaccine is delivered after the AAV vector. ### Claim 18 (depends on 1) The regimen according to claim 1, wherein the AAV vector has a modified capsid comprising a heterologous peptide or polypeptide that enhances antigenicity of the AAV vector. ### Claim 19 (depends on 18) The regimen according to claim 18, wherein the modified capsid comprises a vp2 protein having a peptide fused to its N-terminus. ### Claim 20 (depends on 18) The regimen according to claim 18, wherein the modified capsid comprises a modified vp1 protein having a peptide inserted therein. ### Claim 21 A method of inducing an antigen-specific humoral or T-cell response in a subject, comprising administering: (a) a replication-defective adenovirus vector comprising a first heterologous expression cassette comprising a nucleic acid sequence encoding a product for inducing an antigen-specific humoral or T-cell response to said product under the control of regulatory control sequences which direct expression of said product; and (b) an adeno-associated virus (AAV) vector comprising a second heterologous expression cassette comprising nucleic acid sequence encoding said product for inducing an antigen-specific humoral or T-cell response to said product under the control of regulatory control sequences which direct expression of said product wherein said replication-defective adenovirus vector is administered after said adeno-associated virus (AAV) vector. ### Claim 22 (depends on 21) The method according to claim 21, further comprising administration of multiple adeno-associated virus (AAV) vectors before administration of said replication-defective adenovirus vector. ### Claim 23 (depends on 21) The method according to claim 21, further comprising administration of multiple replication-defective adenovirus vectors after said adeno-associated virus (AAV) vector.