Mature Dendritic Cells Infected with Canarypox Virus Elicit Strong Anti-Human Immunodeficiency Virus CD8(+) and CD4(+) T-Cell Responses from Chronically Infected Individuals

Recombinant canarypox virus vectors containing human immunodeficiency virus type 1 (HIV-1) sequences are promising vaccine candidates, as they replicate poorly in human cells. However, when delivered intramuscularly the vaccines have induced inconsistent and in some cases transient antigen-specific cytotoxic T-cell (CTL) responses in seronegative volunteers. An attractive way to enhance these responses would be to target canarypox virus to professional antigen-presenting cells such as dendritic cells (DCs). We studied (i) the interaction between canarypox virus and DCs and (ii) the T-cell responses induced by DCs infected with canarypox virus vectors containing HIV-1 genes. Mature and not immature DCs resisted the cytopathic effects of canarypox virus and elicited strong effector CD8(+) T-cell responses from chronically infected HIV(+) individuals, e.g., cytolysis, and secretion of gamma interferon (IFN-γ) and β-chemokines. Furthermore, canarypox virus-infected DCs were >30-fold more efficient than monocytes and induced responses that were comparable to those induced by vaccinia virus vectors or peptides. Addition of exogenous cytokines was not necessary to elicit CD8(+) effector cells, although the presence of CD4(+) T cells was required for their expansion and maintenance. Most strikingly, canarypox virus-infected DCs were directly able to stimulate HIV-specific, IFN-γ-secreting CD4 helper responses from bulk as well as purified CD4(+) T cells. Therefore, these results suggest that targeting canarypox virus vectors to mature DCs could potentially elicit both anti-HIV CD8(+) and CD4(+) helper responses in vivo

Upscaling Of Biological Processes And Multiphase Flow In Highly Heterogeneous Media

In order to remediate contamination of our aquifers or optimize the recovery of hydrocarbon from subsurface reservoirs, one must be able to accurately simulate the multiphase flow of fluids through highly heterogeneous media. The fine-scale interfacial interactions greatly influence ow properties particularly in the presence of bioprocesses; these effects must be upscaled through many scales of heterogeneities in the subsurface lithologies. Large-scale correlations of flow properties in the subsurface can cause chanelling, which greatly influences the production or remediation strategies. We will discuss various difficulties in this upscaling process in the context of bioremediation and will present some directions for future research