SIV antigen-specific effects on immune responses induced by vaccination with DNA electroporation and plasmid IL-12

Vaccine. 2013 Oct 1;31(42):4749-58. doi: 10.1016/j.vaccine.2013.08.011. Epub 2013 Aug 14.


Molecular adjuvants are important for augmenting or modulating immune responses induced by DNA vaccination. Promising results have been obtained using IL-12 expression plasmids in a variety of disease models including the SIV model of HIV infection. We used a mouse model to evaluate plasmid IL-12 (pIL-12) in a DNA prime, recombinant adenovirus serotype 5 (rAd5) boost regimen specifically to evaluate the effect of IL-12 expression on cellular and humoral immunity induced against both SIVmac239 Gag and Env antigens. Priming with electroporated (EP) DNA+pIL-12 resulted in a 2-4-fold enhanced frequency of Gag-specific CD4 T cells which was maintained through the end of the study irrespective of the pIL-12 dose, while memory Env-specific CD4+T cells were maintained only at the low dose of pIL-12. There was little positive effect of pIL-12 on the humoral response to Env, and in fact, high dose pIL-12 dramatically reduced SIV Env-specific IgG. Additionally, both doses of pIL-12 diminished the frequency of CD8 T-cells after DNA prime, although a rAd5 boost recovered CD8 responses regardless of the pIL-12 dose. In this prime-boost regimen, we have shown that a high dose pIL-12 can systemically reduce Env-specific humoral responses and CD4T cell frequency, but not Gag-specific CD4+ T cells. These data indicate that it is important to independently characterize individual SIV or HIV antigen immunogenicity in multi-antigenic vaccines as a function of adjuvant dose.

Keywords: Adenovirus; Antibody; DNA; IL-12; T cell.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Adjuvants, Immunologic / genetics
  • Animals
  • Antibodies, Viral / blood
  • Antigens, Viral / genetics
  • Antigens, Viral / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Electroporation
  • Immunologic Memory
  • Interleukin-12 / administration & dosage*
  • Interleukin-12 / genetics
  • Mice
  • Mice, Inbred C57BL
  • SAIDS Vaccines / administration & dosage
  • SAIDS Vaccines / genetics
  • SAIDS Vaccines / immunology*
  • Simian Acquired Immunodeficiency Syndrome / prevention & control*
  • Vaccination / methods*
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / genetics
  • Vaccines, DNA / immunology*


  • Adjuvants, Immunologic
  • Antibodies, Viral
  • Antigens, Viral
  • SAIDS Vaccines
  • Vaccines, DNA
  • Interleukin-12