DNA, or genetic, inoculation mimics aspects of attenuated vaccines in that synthesis of specific foreign proteins is accomplished in the host. These proteins can be processed and presented on the relevant major histocompatibility complex (MHC) antigens and ultimately become the subject of immune surveillance. Very recently, we have described the use of the new technology to generate immune responses in mice against the human immunodeficiency virus type 1 (HIV-1) envelope using a gp160 DNA construct. Further analysis of this technology specifically in regard to HIV vaccine design is clearly important. In this report, we describe the analysis of additional HIV constructs as immunogens in both mice and report the use of this genetic immunization technology in nonhuman primates. In these studies, successful seroconversion occurs in more than 70% of the mice following the second immunization with 100 micrograms of construct DNA; three and four immunizations result in routinely 100% seroconversion of the mice. Furthermore, the same strategy has successfully seroconverted primates following their second inoculation, resulting in the generation of both antiviral and neutralizing antibodies in this animal species. These studies are the first report of which we are aware that demonstrate successful immunization of nonhuman primates through genetic vaccination technology and the first to describe genetic immunization of primates against HIV antigens. This technology has relevance for the development of safe and efficacious immunization strategies against HIV because it provides for relevant antigen production in vivo without the use of infectious agents.
Several recent studies have suggested seemingly contrasting roles of SIRT2 in inflammation: Our previous cell culture study has indicated that SIRT2 siRNA-produced decrease in SIRT2 levels can lead to significant inhibition of lipopolysaccharides (LPS)-induced activation of BV2 microglia, suggesting that SIRT2 is required for LPS-induced microglial activation. In contrast, some studies have suggested that SIRT2 deficiency can lead to increased inflammation. In our current study, we used a mouse model of neuroinflammation to determine the roles of SIRT2 in LPS-induced inflammation. We found that administration of SIRT2 inhibitor AGK2 can significantly decrease LPS-induced increases in CD11b signals and the mRNA of TNF-α and IL-6. We further found that AGK2 can block LPS-induced nuclear translocation of NFκB. In addition, our study has shown that AGK2 can decrease not only LPS-induced increase in TUNEL signals-a marker of apoptosis-like damage, but also LPS-induced increases in the levels of active Caspase-3 and Bax. Collectively, our current in vivo study, together with our previous cell culture study, has suggested that SIRT2 is required for LPS-induced neuroinflammation and brain injury.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.