title: SIV antigen-specific effects on immune responses induced by vaccination with DNA electroporation and plasmid IL-12.
abstract: 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.
authors: International AIDS Vaccine Initiative, 140 58th Street, Brooklyn, NY 11220, USA. Electronic address: rlindsay@iavi.org.
authors: Ross W
authors: RW
authors: Lindsay
authors: Ian
authors: I
authors: Ouellette
authors: Heather E
authors: HE
authors: Arendt
authors: Jennifer
authors: J
authors: Martinez
authors: Joanne
authors: J
authors: DeStefano
authors: Mary
authors: M
authors: Lopez
authors: George N
authors: GN
authors: Pavlakis
authors: Maria J
authors: MJ
authors: Chiuchiolo
authors: Christopher L
authors: CL
authors: Parks
authors: C Richter
authors: CR
authors: King
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000235:genetics; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018274:Electroporation; D007156:Immunologic Memory; D018664:Interleukin-12 / Q000008:administration & dosage* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D014611:Vaccination / Q000379:methods*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D000956:Antigens, Viral; D018449:SAIDS Vaccines; D019444:Vaccines, DNA; D018664:Interleukin-12
keywords: Adenovirus; Antibody; DNA; IL-12; T cell
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