Development of a Minor Histocompatibility Antigen Vaccine Regimen in the Canine Model of Hematopoietic Cell Transplantation

Transplantation. 2015 Oct;99(10):2083-94. doi: 10.1097/TP.0000000000000744.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / metabolism
  • Animals
  • DNA / chemistry
  • Disease Models, Animal
  • Dogs
  • Female
  • Graft vs Tumor Effect*
  • Hematopoietic Stem Cell Transplantation*
  • Immunotherapy, Adoptive
  • Lymphocytes / cytology
  • Male
  • Minor Histocompatibility Antigens / chemistry*
  • Peptides / chemistry
  • Plasmids / metabolism
  • Tissue Donors
  • Transplantation, Homologous


  • Minor Histocompatibility Antigens
  • Peptides
  • DNA