P17-04. Targeting HIV peptides to human dendritic cells via CD40 elicits expansion of multi-epitope polyfunctional CD4+ and CD8+ T cells in HIV patients

International audiencen.

Monitoring the US ATLAS Network Infrastructure with perfSONAR-PS

Global scientific collaborations, such as ATLAS, continue to push the network requirements envelope. Data movement in this collaboration is routinely including the regular exchange of petabytes of datasets between the collection and analysis facilities in the coming years. These requirements place a high emphasis on networks functioning at peak efficiency and availability; the lack thereof could mean critical delays in the overall scientific progress of distributed data-intensive experiments like ATLAS. Network operations staff routinely must deal with problems deep in the infrastructure; this may be as benign as replacing a failing piece of equipment, or as complex as dealing with a multi-domain path that is experiencing data loss. In either case, it is crucial that effective monitoring and performance analysis tools are available to ease the burden of management. We will report on our experiences deploying and using the perfSONAR-PS Performance Toolkit at ATLAS sites in the United States. This software creates a dedicated monitoring server, capable of collecting and performing a wide range of passive and active network measurements. Each independent instance is managed locally, but able to federate on a global scale; enabling a full view of the network infrastructure that spans domain boundaries. This information, available through web service interfaces, can easily be retrieved to create customized applications. The US ATLAS collaboration has developed a centralized “dashboard” offering network administrators, users, and decision makers the ability to see the performance of the network at a glance. The dashboard framework includes the ability to notify users (alarm) when problems are found, thus allowing rapid response to potential problems and making perfSONAR-PS crucial to the operation of our distributed computing infrastructure.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98635/1/1742-6596_396_4_042038.pd

S04-04 OA. HIV-specific responses induced by anti-CD40 targeting antibodies

International audiencen.

P19-26. Directing macaque immune responses with an anti-dendritic cell HIV Gag p24 fusion protein vaccine

International audiencen.

A General Encoding Framework for Representing Network Measurement and Topology Data

SUMMARY Scientific applications are evolving rapidly and rely heavily on the network for data movement, communication, control, and result collection. Efforts to construct intelligent software that is aware of network status as well as features related to the logical and physical aspects of the topology will enable scientists the ability to alter these behaviors and enhance overall performance. The status of the network over time is delivered through monitoring software such as perfSONAR which relies on properly formatted and standardized description formats delivered from the deployed infrastructure [1]. We present a general model used to represent both network measurements collected from performance tools as well as describing the physical and logical characteristics of the underlying network. This system is currently being standardized in the Open Grid Forum to enable other uses within the wider grid and distributed computing community [2]

P16-49. Broad types of cytokines secreted by Gag-specific T cells from HIV infected patients on HAART

International audiencen.

Targeting HIV-1 Env gp140 to LOX-1 Elicits Immune Responses in Rhesus Macaques.

Improved antigenicity against HIV-1 envelope (Env) protein is needed to elicit vaccine-induced protective immunity in humans. Here we describe the first tests in non-human primates (NHPs) of Env gp140 protein fused to a humanized anti-LOX-1 recombinant antibody for delivering Env directly to LOX-1-bearing antigen presenting cells, especially dendritic cells (DC). LOX-1, or 1ectin-like oxidized low-density lipoprotein (LDL) receptor-1, is expressed on various antigen presenting cells and endothelial cells, and is involved in promoting humoral immune responses. The anti-LOX-1 Env gp140 fusion protein was tested for priming immune responses and boosting responses in animals primed with replication competent NYVAC-KC Env gp140 vaccinia virus. Anti-LOX-1 Env gp140 vaccination elicited robust cellular and humoral responses when used for either priming or boosting immunity. Co-administration with Poly ICLC, a TLR3 agonist, was superior to GLA, a TLR4 agonist. Both CD4+ and CD8+ Env-specific T cell responses were elicited by anti-LOX-1 Env gp140, but in particular the CD4+ T cells were multifunctional and directed to multiple epitopes. Serum IgG and IgA antibody responses induced by anti-LOX-1 Env gp140 against various gp140 domains were cross-reactive across HIV-1 clades; however, the sera neutralized only HIV-1 bearing sequences most similar to the clade C 96ZM651 Env gp140 carried by the anti-LOX-1 vehicle. These data, as well as the safety of this protein vaccine, justify further exploration of this DC-targeting vaccine approach for protective immunity against HIV-1

Signaling via interleukin-4, receptor alpha chain is required for successful vaccination against schistosomiasis in BALB/c mice

Radiation-attenuated (RA) schistosome larvae are potent stimulators of innate immune responses at the skin site of exposure (pinna) that are likely to be important factors in the development of Th1-mediated protective immunity. In addition to causing an influx of neutrophils, macrophages, and dendritic cells (DCs) into the dermis, RA larvae induced a cascade of chemokine and cytokine secretion following in vitro culture of pinna biopsy samples. While macrophage inflammatory protein 1 and interleukin-1 (IL-1) were produced transiently within the first few days, the Th1-promoting cytokines IL-12 and IL-18 were secreted at high levels until at least day 14. Assay of C3H/HeJ mice confirmed that IL-12 secretion was not due to lipopolysaccharide contaminants binding Toll-like receptor 4. Significantly, IL-12 p40 secretion was sustained in pinnae from vaccinated mice but not in those from nonprotected infected mice. In contrast, IL-10 was produced from both vaccinated and infected mice. This cytokine regulates IL-12-associated dermal inflammation, since in vaccinated IL-10/ mice, pinna thickness was greatly increased concurrent with elevated levels of IL-12 p40. A significant number of IL-12 p40 cells were detected as emigrants from in vitro-cultured pinnae, and most were within a population of rare large granular cells that were Ia, consistent with their being antigen-presenting cells. Labeling of IL-12 cells for CD11c, CD205, CD8, CD11b, and F4/80 indicated that the majority were myeloid DCs, although a proportion were CD11c F4/80, suggesting that macrophages were an additional source of IL-12 in the skin