Zum Hauptinhalt springen

CMV glycoproteins and recombinant vectors

Oregon Health & Science University
2018
Online Patent

Titel:
CMV glycoproteins and recombinant vectors
Autor/in / Beteiligte Person: Oregon Health & Science University
Link:
Veröffentlichung: 2018
Medientyp: Patent
Sonstiges:
  • Nachgewiesen in: USPTO Patent Grants
  • Sprachen: English
  • Patent Number: 9,862,972
  • Publication Date: January 09, 2018
  • Appl. No: 14/086602
  • Application Filed: November 21, 2013
  • Assignees: Oregon Health & Science University (Portland, OR, US)
  • Claim: 1. 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.
  • Claim: 2. The method of claim 1 , wherein the at least one heterologous antigen comprises an infectious disease antigen or a tumor antigen.
  • Claim: 3. The method of claim 1 , wherein the CMV-seropositive subject is a human or a rhesus macaque.
  • Claim: 4. The method of claim 1 , wherein the recombinant CMV vector comprises one or more of: (1) a point mutation in a nucleic acid sequence encoding US11 or a functional homologue thereof, (2) a frameshift mutation in the nucleic acid sequence encoding US11 or a functional homologue thereof, or (3) a deletion of all or part of the nucleic acid sequence encoding US11 or a functional homologue thereof.
  • Claim: 5. The method of claim 1 , wherein administering comprises intravenous, intramuscular, intraperitoneal, or oral administration of the recombinant CMV vector.
  • Claim: 6. The method of claim 1 , wherein the at least one heterologous antigen is selected from the group consisting of: a Hepatitis B virus antigen; a Hepatitis C virus antigen; a human immunodeficiency virus (HIV) antigen; a simian immunodeficiency virus (SIV) antigen; a Clostridium tetani antigen; a Mycobacterium tuberculosis antigen; and a Plasmodium antigen.
  • Claim: 7. The method of claim 1 , wherein expression of the at least one heterologous antigen is driven by a heterologous antigen-encoding sequence operably linked to a promoter.
  • Claim: 8. The method of claim 7 , wherein the promoter is selected from the group consisting of: a constitutive promoter, an inducible promoter, a non-viral promoter, and a viral promoter.
  • Claim: 9. The method of claim 4 , wherein the recombinant CMV vector comprises a deletion of all of the nucleic acid sequence encoding US11 or a functional homologue thereof.
  • Claim: 10. The method of claim 1 , wherein the recombinant CMV vector encodes the US2 of SEQ ID NO:1, the US3 of SEQ ID NO:2, and the US6 of SEQ ID NO:3.
  • Claim: 11. The method of claim 1 , wherein the at least one heterologous antigen comprises an infectious disease antigen or a tumor antigen, wherein the CMV-seropositive subject is a human cytomegalovirus (HCMV)-seropositive human subject, and wherein the recombinant CMV vector is a recombinant HCMV vector.
  • Claim: 12. The method of claim 8 , wherein the promoter is an EF1-alpha promoter or a CMV-IE promoter.
  • Claim: 13. The method of claim 1 , wherein the at least one heterologous antigen comprises an infectious disease antigen or tumor antigen, wherein the CMV-seropositive subject is a HCMV-seropositive human subject, wherein the recombinant CMV vector is a recombinant HCMV vector, and wherein the recombinant HCMV vector does not express an active US8 or US10 protein.
  • Claim: 14. The method of claim 13 , wherein the recombinant HCMV vector does not express active US8 and US10 proteins.
  • Claim: 15. The method of claim 14 , wherein the recombinant HCMV vector comprises a deletion of all of the nucleic acid sequence encoding US8-US11.
  • Claim: 16. The method of claim 1 , wherein the recombinant CMV vector does not express an active US8 or US10 protein, or a functional homologue thereof.
  • Claim: 17. The method of claim 16 , wherein the recombinant CMV vector does not express active US8 and US10 proteins, or functional homologues thereof.
  • Claim: 18. The method of claim 17 , wherein the recombinant CMV vector comprises a deletion of all of the nucleic acid sequence encoding US8-US11 or functional homologues thereof.
  • Claim: 19. The method of claim 1 , wherein the recombinant CMV vector is a recombinant rhesus CMV (RhCMV) vector.
  • Claim: 20. The method of claim 13 , wherein the at least one heterologous antigen is selected from the group consisting of: an HIV antigen, an SIV antigen, a hepatitis B virus antigen, a hepatitis C virus antigen, a Clostridium tetani antigen, Mycobacterium tuberculosis antigen, and a plasmodium antigen.
  • Claim: 21. The method of claim 11 , wherein the at least one heterologous antigen is selected from the group consisting of: an HIV antigen, an SIV antigen, a hepatitis B virus antigen, a hepatitis C virus antigen, a Clostridium tetani antigen, a Mycobacterium tuberculosis antigen, and a plasmodium antigen.
  • Claim: 22. 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.
  • Claim: 23. The method of claim 22 , wherein the CMV-seropositive subject is a human or a rhesus macaque.
  • Claim: 24. The method of claim 22 , wherein the recombinant CMV vector is a recombinant HCMV vector or a recombinant RhCMV vector.
  • Claim: 25. The method of claim 22 , wherein the recombinant CMV vector comprises a deletion of all of the nucleic acid sequence encoding US8, US10, and US11, or functional homologues thereof.
  • Claim: 26. The method of claim 22 , wherein the nucleic acid sequence encoding the at least one heterologous antigen is located between the nucleic acid sequence encoding US8 or a functional homologue thereof and the nucleic acid sequence encoding US12 or a functional homologue thereof.
  • Claim: 27. The method of claim 26 , wherein the recombinant CMV vector comprises a deletion of all of the nucleic acid sequence encoding US10 and US11, or functional homologues thereof.
  • Claim: 28. The method of claim 22 , wherein the nucleic acid sequence encoding the at least one heterologous antigen is located between the nucleic acid sequence encoding US10 or a functional homologue thereof and the nucleic acid sequence encoding US12 or a functional homologue thereof.
  • Claim: 29. The method of claim 22 , wherein the at least one heterologous antigen comprises an infectious disease antigen or a tumor antigen.
  • Claim: 30. The method of claim 22 , wherein the at least one heterologous antigen is selected from the group consisting of: an HIV antigen, an SIV antigen, a hepatitis B virus antigen, a hepatitis C virus antigen, a Clostridium tetani antigen, a Mycobacterium tuberculosis antigen, and a plasmodium antigen.
  • Claim: 31. 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.
  • Claim: 32. The method of claim 31 , wherein the at least one heterologous antigen comprises an infectious disease antigen or a tumor antigen.
  • Claim: 33. The method of claim 31 , wherein the at least one heterologous antigen is selected from the group consisting of: a hepatitis B virus antigen, a hepatitis C virus antigen, a Clostridium tetani antigen, a Mycobacterium tuberculosis antigen, and a Plasmodium antigen.
  • Claim: 34. 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.
  • Claim: 35. The method of claim 34 , wherein the at least one heterologous antigen is a human papillomavirus antigen.
  • Claim: 36. The method of claim 34 , wherein the at least one heterologous antigen is a HSV antigen.
  • Claim: 37. The method of claim 36 , wherein the HSV antigen is an HSV-1 antigen.
  • Claim: 38. The method of claim 36 , wherein the HSV antigen is an HSV-2 antigen.
  • Claim: 39. The method of claim 34 , wherein the recombinant HCMV vector comprises one or more of: (1) a point mutation in a nucleic acid sequence encoding US11, (2) a frameshift mutation in the nucleic acid sequence encoding US11, or (3) a deletion of all or part of the nucleic acid sequence encoding US11.
  • Claim: 40. The method of claim 39 , wherein the recombinant HCMV vector comprises a deletion of all of the nucleic acid sequence encoding US11.
  • Claim: 41. The method of claim 34 , wherein administering comprises intravenous, intramuscular, intraperitoneal, or oral administration of the recombinant HCMV vector.
  • Claim: 42. The method of claim 34 , wherein expression of the at least one heterologous antigen is driven by a heterologous antigen-encoding sequence operably linked to a promoter.
  • Claim: 43. The method of claim 42 , wherein the promoter is selected from the group consisting of: a constitutive promoter, an inducible promoter, a non-viral promoter, and a viral promoter.
  • Claim: 44. The method of claim 43 , wherein the promoter is an EF1-alpha promoter or a CMV-IE promoter.
  • Claim: 45. The method of claim 34 , wherein the recombinant HCMV vector does not express an active US8 or US10 protein.
  • Claim: 46. The method of claim 45 , wherein the recombinant HCMV vector does not express active US8 and US10 proteins.
  • Claim: 47. The method of claim 46 , wherein the recombinant HCMV vector comprises a deletion of all of the nucleic acid sequence encoding US8-US11.
  • Claim: 48. The method of claim 34 , wherein the recombinant HCMV vector encodes the US2 of SEQ ID NO:1, the US3 of SEQ ID NO:2, and the US6 of SEQ ID NO:3.
  • Claim: 49. The method of claim 34 , wherein the recombinant HCMV vector further comprises a nucleic acid sequence encoding US12, 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.
  • Claim: 50. The method of claim 49 , wherein the recombinant HCMV vector comprises a deletion of all of the nucleic acid sequence encoding US8, US10, and US11.
  • Claim: 51. The method of claim 49 , wherein the recombinant HCMV vector further comprises a nucleic acid encoding US8.
  • Claim: 52. The method of claim 51 , wherein the nucleic acid sequence encoding the at least one heterologous antigen is located between the nucleic acid sequence encoding US8 and the nucleic acid sequence encoding US12.
  • Claim: 53. The method of claim 52 , wherein the recombinant HCMV vector comprises a deletion of all of the nucleic acid sequence encoding US10 and US11.
  • Claim: 54. The method of claim 51 , wherein the recombinant HCMV vector further comprises a nucleic acid encoding US10.
  • Claim: 55. The method of claim 54 , wherein the nucleic acid sequence encoding the at least one heterologous antigen is located between the nucleic acid sequence encoding US10 and the nucleic acid sequence encoding US12.
  • Patent References Cited: 5273876 December 1993 Hock et al. ; 5720957 February 1998 Jones et al. ; 5830745 November 1998 Hock et al. ; 6033671 March 2000 Frueh et al. ; 7892822 February 2011 Koszinowski et al. ; 2002/0176870 November 2002 Schall et al. ; 2003/0118568 June 2003 Crew ; 2004/0086489 May 2004 Schall et al. ; 2004/0248300 December 2004 Preston ; 2005/0064394 March 2005 Liu et al. ; 2005/0118192 June 2005 Boursnell et al. ; 2006/0019369 January 2006 Hahn ; 2008/0199493 August 2008 Picker et al. ; 2009/0148477 June 2009 Bruder et al. ; 2009/0203144 August 2009 Beaton et al. ; 2009/0297555 December 2009 Kemble et al. ; 2013/0136768 May 2013 Picker et al. ; 2013/0142823 June 2013 Picker et al. ; 2013/0156808 June 2013 Jonjic ; 2013/0202638 August 2013 Thirion et al. ; 0521427 January 1993 ; 1988/10311 December 1988 ; 1996/04383 February 1996 ; 2002/062296 August 2002 ; 2006/031264 March 2006 ; 2011/093858 August 2011 ; WO 2011-119920 September 2011 ; 2011/138040 November 2011 ; 2011/143653 November 2011
  • Other References: Brondke H. Human herpesvirus 5, Towne Strain. US6 (NCBI GenBank Acc. No. AAS49004), Dep. Apr. 8, 2004. cited by examiner ; Brondke H. Human herpesvirus 5, Towne Strain. US3 (NCBI GenBank Acc. No. AAS49002). Dep. Apr. 8, 2004. cited by examiner ; Hansen, S.G. et al., “Evasion of CD8+ T cells critical for superinfection by cytomegalovirus”, Science, vol. 328 (102), pp. 102-106 (Apr. 2, 2010). cited by applicant ; Davison et al., “New Genes from Old: Redeployment of dUTPase by Herpesviruses,” Journal of Virology, Oct. 2005, vol. 79, No. 20, pp. 12880-12892. cited by applicant ; Bresnahan, Wade et al., “UL82 Virion Protein Activates Expression of Immediate Early Viral Genes in Human Cytomegalovirus-Infected Cells,” Proc Nat Acad Sci, Dec. 19, 2000, vol. 97, No. 26, pp. 14506-14511. cited by applicant ; Schleiss, Mark R. et al., “Genetically Engineered Live-attenuated Cytomegalovirus (CMV) Vaccines Improve Pregnancy Outcome in the Guinea-pig Model of Congenital CMV Infection,” Retrovirology, Apr. 2008, vol. 5, Suppl I, pp. 1-3. cited by applicant ; Mahmood, Kutubuddin et al., “Human Cytomegalovirus Plasmid-based Amplicon Vector System for Gene Therapy,” Genetic Vaccines and Therapy, Jan. 26, 2005, vol. 3, No. 1:1. cited by applicant ; Mohr, Christian A. et al., “A Spread-Deficient Cytomegalovirus for Assessment of First-Target Cells in Vaccination,” Journal of Virology, Aug. 2010, vol. 84, No. 15, pp. 7730-7742. cited by applicant ; Mohr, Christian A. et al., “Engineering of Cytomegalovirus Genomes for Recombinant Live Herpesvirus Vaccines,” International Journal of Medical Microbiology, 2008, vol. 298, pp. 115-125. cited by applicant ; Murphy, Eain et al., “Coding Potential of Laboratory and Clinical Strains of Human Ctyomegalovirus,” Proc Nat Acad Sci, Dec. 9, 2003, vol. 100, No. 25, pp. 14976-14981. cited by applicant ; Onuffer, James J. et al., “Chemokines, Chemokine Receptors and Small-molecule Antagonists: Recent Developments,” Trends in Pharmacological Sciences, Oct. 2002, vol. 23, No. 10, pp. 459-467. cited by applicant ; Redwood, Alec J. et al., “Use of a Murine Cytomegalovirus K181-Derived Bacterial Artificial Chromosome as a Vaccine Vector for Immunocontraception,” Journal of Virology, Mar. 2005, vol. 79, No. 5, pp. 2998-3008. cited by applicant ; Tessmer, Marlowe S. et al., “Salivary Gland NK Cells are Phenotypically and Functionally Unique,” PLoS Pathogens, Jan. 2011, vol. 7, Issue 1, pp. 1-9. cited by applicant ; Powers, Colin et al., “Rhesus CMV: An Emerging Animal Model for Human CMV,” Med Microbiol Immunol., Jun. 2008, vol. 197, No. 2, pp. 109-115. cited by applicant ; Campadelli-Flume, et al., Editors, “Chapter 15: Betaherpes Viral Genes and Their Functions” Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis. Cambridge: Cambridge University Press, 2007. cited by applicant ; Basta, Sameh, et al., “Inhibitory Effects of Cytomegalovirus Proteins US2 and US11 Point to Contributions from Direct Priming and Cross-Priming in Induction of Vaccinia Virus-Specific CD8+ T Cells,” The Journal of Immunology, 2002, vol. 168, pp. 5403-5408. cited by applicant ; Jones, Thomas R. et al., “Replacement Mutagenesis of the Human Cytomegalovirus Genome: US10 and US11 Gene Products are Nonessential,” Journal of Virology, Nov. 1991, vol. 65, No. 11, pp. 5860-5872. cited by applicant ; Wiertz, Emmanuel J.H. J. et al, “The Human Cytomegalovirus US11 Gene Product Dislocates MHC Class I Heavy Chains from the Endoplasmic Reticulum to the Cytosol,” Cell, Mar. 8, 1996, vol. 84, pp. 769-779. cited by applicant ; Jones, Thomas R. et al., “Multiple Independent Loci Within the Human Cytomegalovirus Unique Short Region Down-Regulate Expression of Major Histocompatibility Complex Class I Heavy Chains,” Journal of Virology, Aug. 1995, vol. 69, No. 8, pp. 4830-4841. cited by applicant ; Chau, Nha H. et al., “Transcriptional Regulation of the Human Cytomegalovirus US11 Early Gene,” Journal of Virology, Feb. 1999, vol. 73, No. 2, pp. 863-870. cited by applicant ; Besold, K. et al., “Immune Evasion Proteins gpUS2 and gpUS11 of Human Cytomegalovirus Incompletely Protect Infected Cells from CD8 T Cell Recognition,” Virology, Jun. 30, 2009, vol. 391, pp. 5-19. cited by applicant ; Chang, W.L. et al., “Cloning of the Full-Length Rhesus Ctyomegalovirus Genome as an Infectious and Self-Excisable Bacterial Artificial Chromosome for Analysis of Viral Pathogenesis,” Journal of Virology, May 2003, vol. 77, No. 9, pp. 5073-5083. cited by applicant ; Hansen, S.G. et al., “Profound Early Control of Highly Pathogenic SIV by an Effector Memory T-cell Vaccine,” Nature, May 26, 2011, vol. 473, pp. 523-530. cited by applicant ; Grimwood, J. et al., “NCBI GenBank Direct Submission,” Acc. No. AC146906, Sub. Nov. 5, 2003. cited by applicant ; “Oxxon Terapeutics Licenses Rights to Xenova's DISC-HSV and DISC-GM-CSF Vector Technolgies,” BusinessWire, Jan. 13, 2005. cited by applicant ; Dudek, Tim et al., “Replication-defective Viruses as Vaccines and Vaccine Vectors,” Virology, 2006, vol. 344, pp. 230-239. cited by applicant ; Mc Gregor, Alistair et al., Molelcular, Biological, and In Vivo Characterization of the Guinea Pig Cytomegalovirus (CMV) Homologs of the Human CMV Matrix Proteins pp71 (UL82) and pp65 (UL83), Journal of Virology, Sep. 2004, vol. 78, No. 18, pp. 9872-9889. cited by applicant ; Lilja, Anders E. et al., “Functional Genetic Analysis of Rhesus Cytomegalovirus: Rh01 is an Epithelial Cell Tropism Factor,” Journal of Virology, Mar. 2008, vol. 82, No. 5, pp. 2170-2181. cited by applicant ; Dunn, Walter, et al., “Functional Profiling of a Human Cytomegalovirus Genome,” Proc Natl Acad Sci, Nov. 25, 2003, vol. 100, No. 24, pp. 14223-14228. cited by applicant ; Cantrell, Stacy R. et al., “Interaction Between the Human Cytomegalovirus UL82 Gene Product (pp71) and hDaxx Regulates Immediate-Early Gene Expression and Viral Replication,” Journal of Virology, Jun. 2005, vol. 79, No. 12, pp. 7792-7802. cited by applicant ; Bresnahan, Wade et al., “Replication of Wild-Type and Mutant Human Cyomegalovirus in Life-Extended Human Diploid Fibroblasts,” Journal of Virology, Nov. 2000, vol. 74, No. 22, pp. 10816-10818. cited by applicant ; Cantrell, Stacy R. et al., “Human Cytomegalovirus (HCMV) UL82 Gene Product (pp71) Relieves hDaxx-Mediated Repression of HMCV Replication,” Journal of Virology, Jun. 2006, vol. 80, No. 12, pp. 6188-6191. cited by applicant ; Moutaftsi, Magdalena et al., “Human Cytomegalovirus Inhibits Maturation and Impairs Function of Monocyte-derived Dendritic Cells,” Blood, Apr. 15, 2002, vol. 99, No. 8, pp. 2913-2921. cited by applicant ; Gorman, Shelley et al., “Prior Infection with Murine Cytomegalovirus (MCMC) limits the Immunocontraceptive Effects of an MCMV Vector Expressing the Mouse-zona-pellucida-3 Protein,” Vaccine, Jun. 2008, vol. 26, pp. 3860-3869. cited by applicant ; Plotkin, Stanley A. et al., “Vaccines for the Prevention of Human Cytomegalovirus Infection,” Reviews of Infectious Diseases, Sep.-Oct. 1990, vol. 12, Supplement 7, pp. S827-S838. cited by applicant ; Olaleye, O.D. et al., “Cytomegalovirus Infection Among Tuberculosis Patients in a Chest Hospital in Nigeria,” Comp. Immun. Microbiol. Infect. Dis. 1990, vol. 13, No. 2, pp. 101-106. cited by applicant ; Kaech, Susan M. et al., “Effector and Memory T-Cell Differentiation: Implications for Vaccine Development,” Nature Reviews, Apr. 2002, vol. 2 pp. 251-262. cited by applicant ; Halary, Franck et al., “Human Cytomegalovirus Binding to DC-SIGN is Required for Dendritic Cell Infection and Target Cell trans-Infection,” Immunity, Nov. 2002, vol. 17, pp. 653-664. cited by applicant ; Marshall, Ker R. et al., “Activity and Intracellular Localization of the Human Cytomegalovirus Protein pp71,” Journal of General Virology, Mar. 2002, vol. 83, pp. 1601-1612. cited by applicant ; Kalejta, Robert F. et al., “Human Cytomegalovirus pp71: A New Viral Tool to Probe the Mechanisms of Cell Cyle Progression and the Oncogenesis Controlled by the Retinoblastoma Family of Tumor Suppressors,” Journal of Cellular Biochemistry, Apr. 2004, vol. 93, pp. 37-45. cited by applicant ; Borst, Eva Maria et al., “Construction of a Cytomegalovirus-Based Amplicon: A Vector with a Unique Transfer Capacity,” Human Gene Therapy, Jul. 1, 2003, vol. 14, pp. 959-970. cited by applicant ; Ulmer, Jeffrey B., “Tuberculosis DNA Vaccines,” Scandinavian Journal of Infectious Disease, 2001, vol. 33, pp. 246-248. cited by applicant ; Wang, Xiuqing et al., “Murine Cytomegalovirus Abortively Infects Human Dendritic Cells, Leading to Expression and Presentation of Virally Vectored Genes,” Journal of Virology, Jul. 2003, vol. 77, No. 13, pp. 7182-7192. cited by applicant ; Hansen, Scott G. et al., “Effector Memory T Cell Responses are Associated with Protection of Rhesus Monkeys from Mucosal Simian Immunodeficiency Virus Challenge,” Nature Medicine, Mar. 2009, vol. 15, No. 3, pp. 293-312. cited by applicant ; Borst, E et al., “Development of a Cytomegalovirus Vector for Somatic Gene Therapy,” Bone Marrow Transplantation, 2000, vol. 25, Supp. 2, pp. S80-S82. cited by applicant ; Karrer et al., “Expansion of Protective CD8+ T-Cell Responses Driven by Recombinant Cytomegaloviruses,” Journal of Virology, Mar. 2004, vol. 78, No. 5, pp. 2255-2264. cited by applicant ; Murphy, Cynthia G. et al.,“Vaccine Protection against Simian Immunodeficiency Virus by Recombinant Strains of Herpes Simplex Virus,” Journal of Virology, Sep. 2000, vol. 74, No. 17, pp. 7745-7754. cited by applicant ; Rizvanov, Albert et al., “Generation of a Recombinant Cytomegalovirus for Expression of a Hantavirus Glycoprotein,” Journal of Virology, 2003, vol. 77, No. 22, pp. 12203-12210. cited by applicant ; Hansen, Scott G., et al., “Complete Sequence and Genomic Analysis of Rhesus Cytomegalovirus,” Journal of Virology, Jun. 2003, vol. 77, No. 12, pp. 6620-6636. cited by applicant ; Hagemeier, SC, “Functional Analysis of the Human Cytomegalovirus UL82 Gene Product PP71 During Virus Replication,” Doctoral Dissertation, The University of Texas Southwestern Medical at Dallas, May 2007, pp. 1-181. cited by applicant ; Ryckman, Brent J. et al., “Characterization of the Human Cytomegalovirus gH/gL/US128-131 Complex That Mediates Entry into Epithelian and Endothelial Cells,” Journal of Virology, Jan. 2008, vol. 82, No. 1, pp. 60-70. cited by applicant ; Oxford, Kristie et al., “Protein Coding Content of the ULb′ Region of Wild-type Rhesus Cytomegalovirus,” Virology, Mar. 30, 2008, vol. 373, No. 1, pp. 181-183. cited by applicant ; Hahn, Gabriele et al., “Human Cytomegalovirus UL 131-128 Genes are Indispensible for Virus Growth in Endothelial Cells and Virus Transfer to Leukocytes,” Journal of Virology, Sep. 2004, vol. 78, No. 18, pp. 10023-10033. cited by applicant
  • Primary Examiner: Gill, Rachel B
  • Attorney, Agent or Firm: Schwabe, Williamson & Wyatt, P.C.

Klicken Sie ein Format an und speichern Sie dann die Daten oder geben Sie eine Empfänger-Adresse ein und lassen Sie sich per Email zusenden.

oder
oder

Wählen Sie das für Sie passende Zitationsformat und kopieren Sie es dann in die Zwischenablage, lassen es sich per Mail zusenden oder speichern es als PDF-Datei.

oder
oder

Bitte prüfen Sie, ob die Zitation formal korrekt ist, bevor Sie sie in einer Arbeit verwenden. Benutzen Sie gegebenenfalls den "Exportieren"-Dialog, wenn Sie ein Literaturverwaltungsprogramm verwenden und die Zitat-Angaben selbst formatieren wollen.

xs 0 - 576
sm 576 - 768
md 768 - 992
lg 992 - 1200
xl 1200 - 1366
xxl 1366 -