title: Development of a Minor Histocompatibility Antigen Vaccine Regimen in the Canine Model of Hematopoietic Cell Transplantation.
abstract: BACKGROUND
  Minor histocompatibility antigen (miHA) vaccines have the potential to augment graft-versus-tumor effects without graft-versus-host disease (GVHD). We used mixed hematopoietic chimerism in the canine model of major histocompatibility complex-matched allogeneic hematopoietic cell transplantation as a platform to develop a miHA vaccination regimen.
  
  
  METHODS
  We engineered DNA plasmids and replication-deficient human adenovirus type 5 constructs encoding large sections of canine SMCY and the entire canine SRY gene.
  
  
  RESULTS
  Priming with replication-deficient human adenovirus type 5 constructs and boosting with ex vivo plasmid-transfected dendritic cells and cutaneous delivery of plasmids with a particle-mediated epidermal delivery device (PMED) in 2 female dogs induced antigen-specific T-cell responses. Similar responses were observed after a prime-boost vaccine regimen in three female hematopoietic cell transplantation donors. Subsequent donor lymphocyte infusion resulted in a significant change of chimerism in 1 of 3 male recipients without any signs of graft-versus-host disease. The change in chimerism in the recipient occurred in association with the development of CD4+ and CD8+ T-cell responses to the same peptide pools detected in the donor.
  
  
  CONCLUSIONS
  These studies describe the first in vivo response to miHA vaccination in a large, outbred animal model without using recipient cells to sensitize the donor. This model provides a platform for ongoing experiments designed to define optimal miHA targets and develop protocols to directly vaccinate the recipient.
authors.affiliation: 1 Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA. 2 Department of Medicine, University of Washington, Seattle, WA. 3 The Center for Emerging and Re-emerging Infectious Diseases, University of Washington, Seattle, WA. 4 Department of Microbiology, University of Washington, Seattle, WA. 5 The Washington National Primate Research Center, University of Washington, Seattle, WA. 6 Division of Vaccine and Infectious Disease, Fred Hutchinson Cancer Research Center, Seattle, WA. 7 Department of Laboratory Medicine, University of Washington, Seattle, WA.
authors.forename: Steven Lawrence
authors.initials: SL
authors.lastname: Rosinski
authors.forename: Brad
authors.initials: B
authors.lastname: Stone
authors.forename: Scott S
authors.initials: SS
authors.lastname: Graves
authors.forename: Deborah H
authors.initials: DH
authors.lastname: Fuller
authors.forename: Stephen C
authors.initials: SC
authors.lastname: De Rosa
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Spies
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Mize
authors.forename: James T
authors.initials: JT
authors.lastname: Fuller
authors.forename: Rainer
authors.initials: R
authors.lastname: Storb
mesh_terms: D000256:Adenoviridae / Q000378:metabolism; D000818:Animals; D004247:DNA / Q000737:chemistry; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D020350:Graft vs Tumor Effect; D018380:Hematopoietic Stem Cell Transplantation; D016219:Immunotherapy, Adoptive; D008214:Lymphocytes / Q000166:cytology; D008297:Male; D015778:Minor Histocompatibility Antigens / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry; D010957:Plasmids / Q000378:metabolism; D014019:Tissue Donors; D014184:Transplantation, Homologous
chemical_list: D015778:Minor Histocompatibility Antigens; D010455:Peptides; D004247:DNA