Anti-Gamma Interferon Antibodies Enhance the Immunogenicity of Recombinant Adenovirus Vectors

作者：Jackson Shawn S; Schmitz Joern E; Letvin Norman L^*

来源：Clinical and Vaccine Immunology, 2011, 18(11): 1969-1978.

DOI：10.1128/CVI.05180-11

Vaccination for eliciting antigen-specific memory CD8(+) T cells may be facilitated by manipulating the pleiotropic effects of gamma interferon (IFN-gamma). We assessed strategies for modulating the contribution of IFN-gamma during the development of antigen-specific cytotoxic T lymphocyte (CTL) populations. We first showed that recombinant IFN-gamma suppressed antigen expression in vitro from a recombinant adenovirus (rAd) vector in a dose-dependent manner and that addition of an anti-IFN-gamma 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-gamma-knockout (GKO) mice than in wild-type mice following immunization with rAd. Since these observations suggested that IFN-gamma might suppress rAd-induced CTL development, we assessed the ability of anti-IFN-gamma Ab administration to augment rAd-elicited CTL in vivo. In fact, blockage of IFN-gamma activity by monoclonal Ab administration was associated with elevated levels of interleukin 7 receptor alpha chain-positive (IL-7R alpha(+)) Env-specific CTL populations postboost. These observations illustrate the utility of an anti-IFN-gamma Ab for potentiating rAd immunizations to effect quantitative and qualitative changes in the effector and memory CTL populations.

• 出版日期2011-11