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.

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

International audiencen.

P18-08. Characterization of CD34+ derived dendritic cells generated in vitro and transfected with HIV gene as potential therapeutic vaccine in macaque

International audiencen.

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

International audiencen.

TLR9- and CD40-Targeting Vaccination Promotes Human B Cell Maturation and IgG Induction via pDC-Dependent Mechanisms in Humanized Mice

Mice reconstituted with a human immune system (humanized mice) provide a robust model to study human immunology, vaccinology, and human infectious diseases. However, the development and function of B cells in humanized mice is impaired. B cells from humanized mice are immature and are impaired in IgM to IgG isotype switch in response to infection or vaccination. In the present study we report that Toll-like receptor 9 (TLR9) agonist CpG-B combined with CD40-targeting vaccination triggered human B cell immunoglobin class-switch from IgM+ to IgG+ B cells in humanized mice. Human B cells from mice vaccinated with CpG-B as adjuvant were more mature in phenotype and produced significant levels of both total IgG and antigen-specific IgG. We found that CpG-B treatment activated human pDCs (plasmacytoid dendritic cells) in vivo to induce interferon-alpha (IFN-α)expression in humanized mice. Pre-depletion of human pDC in vivo abrogated the adjuvant effect of CpG-B. Our results indicate that TLR9 and CD40-targeting vaccination triggers human B cell maturation and immunoglobulin class-switch in a pDC-dependent manner in humanized mice. The findings also shed light on induction of human IgG antibodies in humanized mouse models

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

Unique Structural Modifications Are Present in the Lipopolysaccharide from Colistin-Resistant Strains of \u3ci\u3eAcinetobacter baumannii\u3c/i\u3e

Acinetobacter baumannii is a nosocomial opportunistic pathogen that can cause severe infections, including hospital-acquired pneumonia, wound infections, and sepsis. Multidrug-resistant (MDR) strains are prevalent, further complicating patient treatment. Due to the increase in MDR strains, the cationic antimicrobial peptide colistin has been used to treat A. baumannii infections. Colistin-resistant strains of A. baumannii with alterations to the lipid A component of lipopolysaccharide (LPS) have been reported; specifically, the lipid A structure was shown to be hepta-acylated with a phosphoethanolamine (pEtN) modification present on one of the terminal phosphate residues. Using a tandem mass spectrometry platform, we provide definitive evidence that the lipid A isolated from colistin-resistant A. baumannii MAC204 LPS contains a novel structure corresponding to a diphosphoryl hepta-acylated lipid A structure with both pEtN and galactosamine (GalN) modifications. To correlate our structural studies with clinically relevant samples, we characterized colistin-susceptible and -resistant isolates obtained from patients. These results demonstrated that the clinical colistin-resistant isolate had the same pEtN and GalN modifications as those seen in the laboratory-adapted A. baumannii strain MAC204. In summary, this work has shown complete structure characterization including the accurate assignment of acylation, phosphorylation, and glycosylation of lipid A from A. baumannii, which are important for resistance to colistin

THE FLUIDS AND COMBUSTION FACILITY: ENABLING THE EXPLORATION OF SPACE

The Fluids and Combustion Facility (FCF) is an International Space Station facility designed to support physical and biological research as well as technology experiments in space. The FCF consists of two racks called the Combustion Integrated Rack (CIR) and the Fluids Integrated Rack (FIR). The capabilities of the CIR and the FIR and plans for their utilization will support the President s vision for space exploration. The CIR will accommodate physical research and technology experiments that address needs in the areas of spacecraft fire prevention, detection and suppression, incineration of solid wastes, and power generation. Initial experiments will provide data to support design decisions for exploration spacecraft. The CIR provides a large sealed chamber in a near-weightless environment. The chamber supports many simulated atmospheres including lunar or Martian environments. The FIR will accommodate experiments that address needs for advanced life support, power, propulsion, and spacecraft thermal control systems. The FIR can also serve as a platform for experiments that address human health and performance, medical technologies, and biological sciences. The FIR provides a large volume for payload hardware, reconfigurable diagnostics, customizable software, active rack-level vibration isolation, and data acquisition and management in a nearly uniform temperature environment

The M\u3csub\u3er\u3c/sub\u3e-value of chloroplast coupling factor 1

The Mr of spinach chloroplast coupling factor 1 has been determined by sedimentation equilibrium and by light scattering to be 400 000 ± 24 600 and 407 000 ± 20 000, respectively. These values differ substantially from that obtained previously (325 000) and are consistent with an α3β3γδε{lunate} subunit stoichiometry. © 1983