Xenogeneic immunization in mice using HER2 DNA delivered by an adenoviral vector

Int J Cancer. 2005 Jan 1;113(1):67-77. doi: 10.1002/ijc.20536.


The protective efficacy of xenogeneic vaccination with DNA encoding the HER2 oncogene was evaluated in BALB/c mice transgenic for the transforming form of the neu oncogene, which spontaneously develops carcinomas in all mammary glands. Intramuscular injection of either plasmid DNA followed by electrical stimulation (pVIJ-HER2 with ES) or an adenoviral vector (Ad5-HER2), both expressing the HER2 oncogene, was tested. Immunization using pVIJ-HER2 with ES elicited a cell-mediated response that was much lower than that elicited by the immunization with Ad5-HER2, as measured by the frequency of IFN-gamma-secreting spleen cells. The dominant T-cell epitope of the HER2 protein product (p185) in the BALB/c (H-2(d)) genetic background was identified. While the T-cell response elicited was only partially crossreactive with the corresponding rat epitopes because of sequence variations (89% similarity), a cytotoxic T-lymphocyte activity against the rat immunodominant epitope was also evident. The Ad5-HER2 vaccination induced also antibodies against p185, which crossreacted with the rat protein homolog. Both T- and B-cell responses slowly declined with time. Vaccination with Ad5-HER2 at 6 and 9 weeks of age delayed incidence and reduced multiplicity of tumors in neu transgenic mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Adenoviridae / immunology
  • Animals
  • Antibodies, Heterophile / immunology*
  • Cancer Vaccines / administration & dosage
  • Cancer Vaccines / genetics
  • Cancer Vaccines / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Epitopes, B-Lymphocyte
  • Epitopes, T-Lymphocyte
  • Female
  • Flow Cytometry
  • Genes, erbB-2 / immunology*
  • Genetic Vectors* / genetics
  • Genetic Vectors* / immunology
  • Immunodominant Epitopes
  • Interferon-gamma
  • Mammary Neoplasms, Experimental / immunology*
  • Mammary Neoplasms, Experimental / prevention & control
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred Strains
  • Mice, Transgenic
  • Plasmids / genetics
  • Plasmids / immunology
  • Rats
  • Receptor, ErbB-2 / genetics*
  • Receptor, ErbB-2 / immunology
  • T-Lymphocytes, Cytotoxic / immunology
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / genetics
  • Vaccines, DNA / immunology*


  • Antibodies, Heterophile
  • Cancer Vaccines
  • Epitopes, B-Lymphocyte
  • Epitopes, T-Lymphocyte
  • Immunodominant Epitopes
  • Vaccines, DNA
  • Interferon-gamma
  • Receptor, ErbB-2