title: Anti-gamma interferon antibodies enhance the immunogenicity of recombinant adenovirus vectors.
abstract: Vaccination for eliciting antigen-specific memory CD8(+) T cells may be facilitated by manipulating the pleiotropic effects of gamma interferon (IFN-γ). We assessed strategies for modulating the contribution of IFN-γ during the development of antigen-specific cytotoxic T lymphocyte (CTL) populations. We first showed that recombinant IFN-γ suppressed antigen expression in vitro from a recombinant adenovirus (rAd) vector in a dose-dependent manner and that addition of an anti-IFN-γ antibody (Ab) eliminated this suppression. Consistent with these in vitro findings, we found that HIV-1 envelope (Env)-specific CTL responses were higher in IFN-γ-knockout (GKO) mice than in wild-type mice following immunization with rAd. Since these observations suggested that IFN-γ might suppress rAd-induced CTL development, we assessed the ability of anti-IFN-γ Ab administration to augment rAd-elicited CTL in vivo. In fact, blockage of IFN-γ activity by monoclonal Ab administration was associated with elevated levels of interleukin 7 receptor alpha chain-positive (IL-7Rα(+)) Env-specific CTL populations postboost. These observations illustrate the utility of an anti-IFN-γ Ab for potentiating rAd immunizations to effect quantitative and qualitative changes in the effector and memory CTL populations.
authors: Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA.
authors: Shawn S
authors: SS
authors: Jackson
authors: Jörn E
authors: JE
authors: Schmitz
authors: Norman L
authors: NL
authors: Letvin
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000256:Adenoviridae / Q000235:genetics*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000235:genetics; D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D005822:Genetic Vectors; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D007371:Interferon-gamma / Q000037:antagonists & inhibitors*; D051379:Mice; D008807:Mice, Inbred BALB C; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D000906:Antibodies; D000911:Antibodies, Monoclonal; D014614:Vaccines, Synthetic; D054299:env Gene Products, Human Immunodeficiency Virus; D007371:Interferon-gamma