Protein subunit vaccines offer important potential advantages over live vaccine vectors, but generally elicit weaker and shorter-lived cellular immune responses. Here we investigate the use of pH-responsive, endosomolytic polymer nanoparticles that were originally developed for RNA delivery as vaccine delivery vehicles for enhancing cellular and humoral immune responses. Micellar nanoparticles were assembled from amphiphilic diblock copolymers composed of an ampholytic core-forming block and a re-designed polycationic corona block doped with thiol-reactive pyridyl disulfide groups to enable dual-delivery of antigens and immunostimulatory CpG oligodeoxynucleotide (CpG ODN) adjuvants. Polymers assembled into 23 nm particles with simultaneous packaging of CpG ODN and a thiolated protein antigen, ovalbumin (ova). Conjugation of ova to nanoparticles significantly enhanced antigen cross-presentation in vitro relative to free ova or an unconjugated, physical mixture of the parent compounds. Subcutaneous vaccination of mice with ova-nanoparticle conjugates elicited a significantly higher CD8+ T cell response (0.5% IFN-ɣ+ of CD8+) compared to mice vaccinated with free ova or a physical mixture of the two components. Significantly, immunization with ova-nanoparticle conjugates electrostatically complexed with CpG ODN (dual-delivery) enhanced CD8+ T cell responses (3.4% IFN-ɣ+ of CD8+) 7-, 18-, and 8-fold relative to immunization with conjugates, ova administered with free CpG, or a formulation containing free ova and CpG complexed to micelles, respectively. Similarly, dual-delivery carriers significantly increased CD4+IFN-ɣ+ (Th1) responses, and elicited a balanced IgG1/IgG2c antibody response. Intradermal administration further augmented cellular immune responses, with dual-delivery carriers inducing ~7% antigen-specific CD8+ T cells. This work demonstrates the ability of pH-responsive, endosomolytic nanoparticles to actively promote antigen cross-presentation and augment cellular and humoral immune responses via dual-delivery of protein antigens and CpG ODN. Hence, pH-responsive polymeric nanoparticles offer promise as a delivery platform for protein subunit vaccines.

We report record high breakdown voltages up to 340 and 230 V realized on unintentionally doped (1.5 μm gate length) and Si doped (1 μm gate length) AlGaN/GaN modulation doped field effect transistors (MODFETs), respectively. The devices also have large transconductances up to 140 mS/mm and a full channel current of 150–400 mA/mm. The Si doped MODFET sample demonstrated a very high room temperature mobility of 1500 cm2/Vs. With these specifications, GaN field effect transistors as microwave power devices are practical.

Synthetic subunit vaccines need to induce CD8+ cytotoxic T-cell (CTL) responses for effective vaccination against intracellular pathogens. Most subunit vaccines primarily generate humoral immune responses, with a weaker than desired CD8+ cytotoxic T-cell response. Here, a neutral, pH-responsive polymer micelle carrier that alters intracellular antigen trafficking was shown to enhance CD8+ T-cell responses with a correlated increase in cytosolic delivery and a decrease in exocytosis. Polymer diblock carriers consisted of a N-(2-hydroxypropyl) methacrylamide corona block with pendant pyridyl disulfide groups for reversible conjugation of thiolated ovalbumin, and a tercopolymer ampholytic core-forming block composed of propylacrylic acid (PAA), dimethylaminoethyl methacrylate (DMAEMA), and butyl methacrylate (BMA). The diblock copolymers self-assembled into 25–30 nm diameter micellar nanoparticles. Conjugation of ovalbumin to the micelles significantly enhanced antigen cross-presentation in vitro relative to free ovalbumin, an unconjugated physical mixture of ovalbumin and polymer, and a non pH-responsive micelle-ovalbumin control. Mechanistic studies in a murine dendritic cell line (DC2.4) demonstrated micelle-mediated enhancements in intracellular antigen retention and cytosolic antigen accumulation. Approximately 90% of initially internalized ovalbumin-conjugated micelles were retained in cells after 1.5 h, compared to only ~40% for controls. Furthermore, cells dosed with conjugates displayed 67-fold higher cytosolic antigen levels relative to soluble ovalbumin 4 h post uptake. Subcutaneous immunization of mice with ovalbumin-polymer conjugates significantly enhanced antigen-specific CD8+ T cell responses (0.4 % IFN-γ+ of CD8+) compared to immunization with soluble protein, ovalbumin and polymer mixture, and the control micelle without endosome-releasing activity. Additionally, pH-responsive carrier facilitated antigen delivery to antigen presenting cells in the draining lymph nodes. As early as 90 min post injection ova-micelle conjugates were associated with 28% and 55% of dendritic cells and macrophages, respectively. After 24 h, conjugates preferentially associated with dendritic cells, affording 30-, 3-, and 3-fold enhancements in uptake relative to free protein, physical mixture, and the non pH-responsive conjugate controls, respectively. These results demonstrate the potential of pH-responsive polymeric micelles for use in vaccine applications that rely on CD8+ T cell activation.

Raman and photoluminescence characterization of focused ion beam patterned InGaN/GaN multi-quantum-wells nanopillar arrayEffects of growth interruption on the optical and the structural properties of InGaN/GaN quantum wells grown by metalorganic chemical vapor deposition GaN nanopillar and nanostripe arrays with embedded InGaN / GaN multi-quantum wells ͑MQWs͒ were fabricated by holographic lithography and subsequent reactive ion etching. Etch related damage of the nanostructures was successfully healed through annealing in NH 3 /N 2 mixtures under optimized conditions. The nanopatterned samples exhibited enhanced luminescence in comparison to the planar wafers. X-ray reciprocal space maps recorded around the asymmetric ͑1015͒ reflection revealed that the MQWs in both nanopillars and nanostripes relaxed after nanopatterning and adopted a larger in-plane lattice constant than the underlying GaN layer. The pillar relaxation process had no measurable effect on the Stokes shift typically observed in MQWs on c-plane GaN, as evaluated by excitation power dependent photoluminescence ͑PL͒ measurements. Angular-resolved PL measurements revealed the extraction of guided modes from the nanopillar arrays.

Growth conditions for AlN in two dimensional (2D) and three dimensional (3D) growth modes were explored on SiC using metal organic chemical vapor deposition. High quality AlN layers were obtained by alternating between 3D and 2D growth modes, referred to as modulation growth (MG). Long parallel atomic terraces without step terminations were observed in atomic force microscopy (AFM) scans of MG AlN, indicating a reduced dislocation density. X-ray diffraction rocking curves yielded full widths at half maximum (FWHM) of 86 and 363arcsec for the (002) and (102) reflections, respectively, giving further evidence of low dislocation density in the film. 3D-2D MG also releases some of the tensile strain in the AlN film, enabling the growth of thick, crack-free AlN on SiC substrates.