27 results on '"Chen, Dexiang"'
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2. Probing Oxidation Mechanisms in Plasmonic Catalysis: Unraveling the Role of Reactive Oxygen Species.
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Wei, Yunjia, Fan, Xingce, Chen, Dexiang, Zhu, Xiangnan, Yao, Lei, Zhao, Xing, Tang, Xiao, Wang, Jiawei, Zhang, Yuanjian, Qiu, Teng, and Hao, Qi
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- 2024
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3. Probing Oxidation Mechanisms in Plasmonic Catalysis: Unraveling the Role of Reactive Oxygen Species
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Wei, Yunjia, Fan, Xingce, Chen, Dexiang, Zhu, Xiangnan, Yao, Lei, Zhao, Xing, Tang, Xiao, Wang, Jiawei, Zhang, Yuanjian, Qiu, Teng, and Hao, Qi
- Abstract
Plasmon-induced oxidation has conventionally been attributed to the transfer of plasmonic hot holes. However, this theoretical framework encounters challenges in elucidating the latest experimental findings, such as enhanced catalytic efficiency under uncoupled irradiation conditions and superior oxidizability of silver nanoparticles. Herein, we employ liquid surface-enhanced Raman spectroscopy (SERS) as a real-time and in situtool to explore the oxidation mechanisms in plasmonic catalysis, taking the decarboxylation of p-mercaptobenzoic acid (PMBA) as a case study. Our findings suggest that the plasmon-induced oxidation is driven by reactive oxygen species (ROS) rather than hot holes, holding true for both the Au and Ag nanoparticles. Subsequent investigations suggest that plasmon-induced ROS may arise from hot carriers or energy transfer mechanisms, exhibiting selectivity under different experimental conditions. The observations were substantiated by investigating the cleavage of the carbon–boron bonds. Furthermore, the underlying mechanisms were clarified by energy level theories, advancing our understanding of plasmonic catalysis.
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- 2024
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4. Formulation and preclinical studies with a trivalent rotavirus P2-VP8 subunit vaccine
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Lakatos, Kyle, McAdams, David, White, Jessica A., and Chen, Dexiang
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ABSTRACTMore effective rotavirus vaccines are essential for preventing extensive diarrheal morbidity and mortality in children under five years of age in low-resource regions. Nonreplicating rotavirus vaccines (NRRV) administered parenterally provide an alternate vaccination method to the current licensed oral vaccine. Live attenuated vaccines and may generate increased efficacy in low-resource settings because the parenteral administration route bypasses some of the challenges associated with oral administration, including differences in intestinal environments. Work described here supports development of a trivalent NRRV vaccine for parenteral administration to avoid complications of the gastrointestinal route. Recombinant VP8* subunit proteins representing some of the most prevalent strains of rotavirus infecting humans – DS-1 (P[4]), 1076 (P[6]), and Wa (P[8]) – were combined with an aluminum adjuvant and the P2 epitope of tetanus toxoid to enhance the immune response to this NRRV antigen. Vaccine formulation development included selection of aluminum hydroxide (Alhydrogel®) as an appropriate adjuvant as well as an optimal buffer to maintain antigen stability and optimize antigen binding to the adjuvant. Characterization assays were used to select the lead vaccine formulation and monitor formulation stability. The NRRV liquid formulation was stable for one year at 2°C to 8°C and four weeks at 37°C. Immunogenicity of the NRRV formulation was evaluated using a guinea pig model, where we demonstrated that the adjuvant provided a 20-fold increase in neutralization titer against a homologous antigen and that the P2-fusion also enhanced the serum neutralizing antibody responses. This vaccine candidate is currently being evaluated in human clinical trials.
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- 2020
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5. Fates of atmospheric deposited nitrogen in an Asian tropical primary forest.
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Wang, Ang, Zhu, Weixing, Gundersen, Per, Phillips, Oliver L., Chen, Dexiang, and Fang, Yunting
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FOREST ecology ,CARBON sequestration in forests ,TROPICAL forests ,MOUNTAIN forests ,ATMOSPHERIC nitrogen - Abstract
The impacts of increasing nitrogen (N) deposition on forest ecosystems, including on carbon (C) sequestration, largely depend on the extent to which forests are N-limited and so whether and where deposited N is retained within the ecosystem. The 15 N tracer method can provide excellent insight into the ecosystem fates of N, but while it has been extensively used in temperate forests it has yet to be sufficiently employed in tropical forests, which are often thought not to be N-limited. Here, we used stable isotope 15 NH 4 + and 15 NO 3 − tracers applied as solutions to the forest floor to examine the fates of different forms of N in a tropical montane primary forest with low background atmospheric N deposition (6 kg N ha −1 yr −1 ) in China. We found that a substantial amount of 15 N was assimilated by plants over time and significantly more 15 N was recovered following 15 NO 3 − addition than following 15 NH 4 + addition: 7% and 16% of 15 N were recovered three months after the respective 15 NH 4 + and 15 NO 3 − tracer additions and 11% and 29% respectively after one year. In contrast to plants, the organic layer was only an important short-term sink for deposited N: while 21% and 12% of the 15 N from 15 NH 4 + and 15 NO 3 − additions were accumulated in the organic layer after three months, more than half of the retained 15 N was lost after one year. Mineral soil was the largest sink for deposited N, and the 15 N retained in soil was relatively stable over time for both N forms, with 39% and 32% of the initial 15 N input recovered after one year for 15 NH 4 + and 15 NO 3 − tracer additions, respectively. Overall, the total ecosystem 15 N recovery one year after the 15 NH 4 + and 15 NO 3 − tracer additions was large (60% and 66% respectively), and not significantly different from total recovery after three months, suggesting that a large proportion of deposited N could be retained in the longer term. Based on the measured fate of 15 N one year after labeling and the C:N ratios of different plant components, this tropical forest’s carbon sequestration efficiency is calculated to be 17 kg C per kg N added, comparable to the values reported for temperate and boreal forests in Europe and North America and indicating substantial N limitation of this tropical forest. Our results suggest that anthropogenic N input in moderate levels may contribute to enhance C sequestration in some tropical forests, without significant long-term loss of N to the environment. [ABSTRACT FROM AUTHOR]
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- 2018
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6. Long-term phosphorus addition alleviates CO2 and N2O emissions via altering soil microbial functions in secondary rather primary tropical forests.
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Chen, Jie, Ma, Xiaomin, Lu, Xiankai, Xu, Han, Chen, Dexiang, Li, Yanpeng, Zhou, Zhang, Li, Yide, Ma, Suhui, and Yakov, Kuzyakov
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TROPICAL forests ,GREENHOUSE gases ,CARBON emissions ,SECONDARY forests ,FOREST soils ,SOILS - Abstract
Tropical forests, where the soils are nitrogen (N) rich but phosphorus (P) poor, have a disproportionate influence on global carbon (C) and N cycling. While N deposition substantially alters soil C and N retention in tropical forests, whether P input can alleviate these N-induced effects by regulating soil microbial functions remains unclear. We investigated soil microbial taxonomy and functional traits in response to 10-year independent and interactive effects of N and P additions in a primary and a secondary tropical forest in Hainan Island. In the primary forest, N addition boosted oligotrophic bacteria and phosphatase and enriched genes responsible for C-, P-mineralization, nitrification and denitrification, suggesting aggravated P limitation while N excess. This might stimulate P excavation via organic matter mineralization, and enhance N losses, thereby increasing soil CO 2 and N 2 O emissions by 86% and 110%, respectively. Phosphorus and NP additions elevated C-mining enzymes activity mainly due to intensified C limitation, causing 82% increase in CO 2 emission. In secondary forest, P and NP additions reduced phosphatase activity, enriched fungal copiotrophs and increased microbial biomass, suggesting removal of nutrient deficiencies and stimulation of fungal growth. Meanwhile, soil CO 2 emission decreased by 25% and N 2 O emission declined by 52–82% due to alleviated P acquisition from organic matter decomposition and increased microbial C and N immobilization. Overall, N addition accelerates most microbial processes for C and N release in tropical forests. Long-term P addition increases C and N retention via reducing soil CO 2 and N 2 O emissions in the secondary but not primary forest because of strong C limitation to microbial N immobilization. Further, the seasonal and annual variations in CO 2 and N 2 O emissions should be considered in future studies to test the generalization of these findings and predict and model dynamics in greenhouse gas emissions and C and N cycling. [Display omitted] • N and P inputs shift soil fungi towards copiotrophs and bacteria towards oligotrophs in tropical forest. • Soil microbial responses to nutrient inputs differs between primary and secondary forests. • P boosts fungal growth and N retention in secondary forest, reducing soil CO 2 and N 2 O efflux. • N enhances microbial P excavation and denitrification in primary forest, raising CO 2 and N 2 O efflux. • Soil N:P ratio regulates microbial C and N retention and release capacity under N and P inputs. [ABSTRACT FROM AUTHOR]
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- 2023
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7. Serum and mucosal antibody responses to inactivated polio vaccine after sublingual immunization using a thermoresponsive gel delivery system
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White, Jessica A, Blum, Jeremy S, Hosken, Nancy A, Marshak, Joshua O, Duncan, Lauren, Zhu, Changcheng, Norton, Elizabeth B, Clements, John D, Koelle, David M, Chen, Dexiang, Weldon, William C, Steven Oberste, M, and Lal, Manjari
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Administering vaccines directly to mucosal surfaces can induce both serum and mucosal immune responses. Mucosal responses may prevent establishment of initial infection at the port of entry and subsequent dissemination to other sites. The sublingual route is attractive for mucosal vaccination, but both a safe, potent adjuvant and a novel formulation are needed to achieve an adequate immune response. We report the use of a thermoresponsive gel (TRG) combined with a double mutant of a bacterial heat-labile toxin (dmLT) for sublingual immunization with a trivalent inactivated poliovirus vaccine (IPV) in mice. This TRG delivery system, which changes from aqueous solution to viscous gel upon contact with the mucosa at body temperature, helps to retain the formulation at the site of delivery and has functional adjuvant activity from the inclusion of dmLT. IPV was administered to mice either sublingually in the TRG delivery system or intramuscularly in phosphate-buffered saline. We measured poliovirus type-specific serum neutralizing antibodies as well as polio-specific serum Ig and IgA antibodies in serum, saliva, and fecal samples using enzyme-linked immunosorbent assays. Mice receiving sublingual vaccination via the TRG delivery system produced both mucosal and serum antibodies, including IgA. Intramuscularly immunized animals produced only serum neutralizing and binding Ig but no detectable IgA. This study provides proof of concept for sublingual immunization using the TRG delivery system, comprising a thermoresponsive gel and dmLT adjuvant.
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- 2014
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8. A freeze-stable formulation for DTwP and DTaP vaccines
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Xue, Honggang, Yang, Bangling, Kristensen, Debra D, and Chen, Dexiang
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Inadvertent vaccine freezing often occurs in the cold chain and may cause damage to freeze‑sensitive vaccines. Liquid vaccines that contain aluminum salt adjuvants are particularly vulnerable. Polyol cryoprotective excipients have been shown to prevent freeze damage to hepatitis B vaccine. In this study, we examined the freeze-protective effect of propylene glycol on diphtheria-tetanus-pertussis-whole-cell (DTwP) and acellular (DTaP) vaccines. Pilot lots of DTwP and DTaP formulated with 7.5% propylene glycol underwent 3 freeze-thaw treatments. The addition of propylene glycol had no impact on pH, particle size distribution, or potency of the vaccines prior to freeze-thaw treatment; the only change noted was an increase in osmolality. The potencies and the physical properties of the vaccines containing cryoprotectant were maintained after freeze-thawing and for 3 months in accelerated stability studies. The results from this study indicate that formulating vaccines with propylene glycol can protect diphtheria-tetanus-pertussis vaccines against freeze damages.
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- 2014
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9. Preparation of Acrylate Copolymer Containing Fluorine and Silicon Latex.
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Dai Weishuai, Xu Lin, Xie Hongde, and Chen Dexiang
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ACRYLATES ,COPOLYMERS ,LATEX ,FLUORINE ,SILICON - Abstract
In this paper, acrylate copolymer latexes containing fluorine and silicon were prepared via semi continuous emulsion copolymerization in the presence of dodecyl-benzenesulfonic acid (DBSA). The effects of the contents of catalyst and monomers on the stability of emulsion were systemically investigated. FTIR, TEM and TGA were used to analyze the properties of the latexes and films. The results indicated that when the amount of D
F 3 was 20%, DBSA was 0.7%, VTES was 3%, the final product was much more stable. The average particle size of the latexes was about 88 nm with a narrow distribution. The thermal stability of the film was improved and the water absorption rate was declined by the addition of fluorosilicone monomer. [ABSTRACT FROM AUTHOR]- Published
- 2012
10. Biomass and carbon dynamics of a tropical mountain rain forest in China
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Chen, DeXiang, Li, YiDe, Liu, HePing, Xu, Han, Xiao, WenFa, Luo, TuShou, Zhou, Zhang, and Lin, MingXian
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Biometric inventories for 25 years, from 1983 to 2005, indicated that the Jianfengling tropical mountain rain forest in Hainan, China, was either a source or a modest sink of carbon. Overall, this forest was a small carbon sink with an accumulation rate of (0.56±0.22) Mg C ha−1yr−1, integrated from the long-term measurement data of two plots (P9201 and P8302). These findings were similar to those for African and American rain forests ((0.62±0.23) Mg C ha−1yr−1). The carbon density varied between (201.43±29.38) Mg C ha−1and (229.16±39.2) Mg C ha−1, and averaged (214.17±32.42) Mg C ha−1for plot P9201. Plot P8302, however, varied between (223.95±45.92) Mg C ha−1and (254.85±48.86) Mg C ha−1, and averaged (243.35±47.64) Mg C ha−1. Quadratic relationships were found between the strength of carbon sequestration and heavy rainstorms and dry months. Precipitation and evapotranspiration are two major factors controlling carbon sequestration in the tropical mountain rain forest.
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- 2010
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11. Stabilization of vaccines: Lessons learned
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Kristensen, Debra and Chen, Dexiang
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- 2010
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12. A heat-stable hepatitis B vaccine formulation
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Jezek, Jan, Chen, Dexiang, Watson, Lynne, Crawford, Jill, Perkins, Shalimar, Tyagi, Anil, and Jones Braun, LaToya
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The purpose of the present study was to develop a formulation of recombinant hepatitis B vaccine with improved stability at elevated temperatures. A validated, in vitro, antigen reactivity assay was used to measure the stability of the vaccine. The formulation development focused on modification of the interactions between the antigen and aluminum hydroxide adjuvant and subsequent optimization of the ionic aqueous environment of the adsorbed vaccine. A formulation of hepatitis B vaccine containing 40 mM histidine and 40 mM phosphate at pH 5.2 had considerably improved stability at elevated temperatures as measured by the in vitro antigen reactivity assay. The formulation exhibited 9-week stability at 55°C and was subsequently shown to be stable both at 37°C and at 45°C for at least 6 months based on the in vitro antigen reactivity and immunogenicity in mice. The formulation comprises only excipients which have a history of safe use in approved drug products. The new vaccine formulation has the potential to be used outside the cold chain for part of its shelf life. This may improve the immunization coverage, simplify the logistics for outreach immunization, and ensure the potency of the vaccine in areas where the cold chain is insufficient.
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- 2009
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13. Characterization of the freeze sensitivity of a hepatitis B vaccine
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Chen, Dexiang, Tyagi, Anil, Carpenter, John, Perkins, Shalimar, Sylvester, David, Guy, Mark, Kristensen, Debra D., and Jones Braun, LaToya
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Recent studies have revealed that vaccines containing aluminum adjuvant are exposed to sub-zero temperatures while in the cold chain more frequently than was previously believed. This raises concerns that these freeze-sensitive vaccines may be damaged and offer inadequate protection. This study was undertaken to characterize the immediate qualitative changes of one such vaccine, hepatitis B, caused by freeze exposure. Hepatitis B vaccine was subjected to freezing temperatures ranging from 0°C to -20°C for up to three episodes with durations ranging from 1 hour to 7 days. The vaccine was analyzed for freezing point, particle size distribution, tertiary structure, and in vitro and in vivo potency. Whether or not hepatitis B vaccine freezes was shown to be dependent on an array of factors including temperature, rate of temperature change, duration of exposure, supercooling effects, and vibration. Vaccine exposed to “mild” freezing (-4°C or warmer) temperatures did not freeze and remained qualitatively unaltered. Single or repeated freezing events at temperatures of -10°C or lower were associated with aggregation of the adjuvant-antigen particles, structural damage of the antigen, and reduction of immunogenicity in mice. Damage to the vaccine increased with duration of freezing, lower temperature, and the number of freezing episodes. With vibration, vaccine froze at -6°C after 1 hour and damage occurred. Freezing and freeze damage to vaccines containing aluminum adjuvant represents a real risk to effectiveness of immunizations and should be prevented by strengthening the cold chain system or, alternatively, development of freeze-stable vaccine formulations.
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- 2009
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14. An antigen-independent but not antigen-specific TH1 response provides protection in the murine airway inflammation model
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Burger, Melissa S., Zuleger, Cindy L., Chu, Qili, Gao, Xiaoyan, Payne, Lendon G., and Chen, Dexiang
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Atopic disorders are associated with an imbalanced THcell response biased toward a strong TH2 type, resulting in excessive production of IgE antibodies, eosinophil recruitment and activation, and mast cell degranulation. Restoring the TH1-TH2 balance by increasing the antigen-specific TH1 response has been pursued for specific allergy immunotherapy. Synthetic oligodeoxynucleotides containing unmethylated CG dinucleotides (CpG) are strong TH1 adjuvants and are being investigated for allergy immunotherapy.
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- 2004
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15. Influenza Vaccine Powder Formulation Development: Spray‐Freeze‐Drying and Stability Evaluation
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Maa, Yuh‐Fun, Ameri, Mahmoud, Shu, Cassandra, Payne, Lendon G., and Chen, Dexiang
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The purpose of this study was to develop a spray‐freeze‐drying (SFD) process for preparing an influenza vaccine dry powder formulation suitable for epidermal powder immunization. After preformulation of two types of flu vaccines, their dry‐powder formulations were prepared by SFD. Powder properties and physical stability were determined using particle size analysis, tap density measurement, scanning electron microscopy, optical microscopy, and moisture content analysis. Chemical and biochemical stability of vaccine antigens was determined by sodium dodecyl sulfate–polyacrylamide gel electrophoresis, single radial immunodiffusion assay, and in vivoimmunogenicity in a mouse model. We demonstrated that SFD could produce high‐density particles—a critical parameter for effective skin penetration. From the stability perspective, the stress posed by SFD was mild because the antigen in the dry powder retained its stability, potency, and immunogenicity. Among several formulations screened, we noted that formulation composition has a significant role in the powder's long‐term physical and biochemical stability. One formulation, in particular, containing sub‐unit vaccine (45 μg of antigen in 1 mg of powder) with a tertiary mixture of trehalose, mannitol, and dextran, exhibited excellent overall stability, including acceptable biochemical stability after being exposed to a highly humid environment. After all, we have not only demonstrated the suitability of SFD to prepare powders for epidermal powder immunization but also developed a systematic formulation development strategy that allowed the optimization of an influenza vaccine dry powder formulation. More important, this study led to the selection of a formulation system that had been successfully tested in a human clinical study. © 2004 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:1912–1923, 2004
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- 2004
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16. Influenza vaccine powder formulation development: spray‐freeze‐drying and stability evaluation
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Maa, Yuh‐Fun, Ameri, Mahmoud, Shu, Cassandra, Payne, Lendon G., and Chen, Dexiang
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The purpose of this study was to develop a spray‐freeze‐drying (SFD) process for preparing an influenza vaccine dry powder formulation suitable for epidermal powder immunization. After preformulation of two types of flu vaccines, their dry‐powder formulations were prepared by SFD. Powder properties and physical stability were determined using particle size analysis, tap density measurement, scanning electron microscopy, optical microscopy, and moisture content analysis. Chemical and biochemical stability of vaccine antigens was determined by sodium dodecyl sulfate–polyacrylamide gel electrophoresis, single radial immunodiffusion assay, and in vivo immunogenicity in a mouse model. We demonstrated that SFD could produce high‐density particles—a critical parameter for effective skin penetration. From the stability perspective, the stress posed by SFD was mild because the antigen in the dry powder retained its stability, potency, and immunogenicity. Among several formulations screened, we noted that formulation composition has a significant role in the powder's long‐term physical and biochemical stability. One formulation, in particular, containing sub‐unit vaccine (45 μg of antigen in 1 mg of powder) with a tertiary mixture of trehalose, mannitol, and dextran, exhibited excellent overall stability, including acceptable biochemical stability after being exposed to a highly humid environment. After all, we have not only demonstrated the suitability of SFD to prepare powders for epidermal powder immunization but also developed a systematic formulation development strategy that allowed the optimization of an influenza vaccine dry powder formulation. More important, this study led to the selection of a formulation system that had been successfully tested in a human clinical study. © 2004 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:1912–1923, 2004
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- 2004
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17. Spray-Coating for Biopharmaceutical Powder Formulations: Beyond the Conventional Scale and Its Application
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Maa, Yuh-Fun, Ameri, Mahmoud, Rigney, Robert, Payne, Lendon, and Chen, Dexiang
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Purpose:Fluid-bed spray-coating process is widely used to prepare non-protein pharmaceutical solid dosage forms using macro-size seed particles (200-1000 μm) at kilogram batch sizes. In this study we developed a small-scale fluid-bed spray-coating process (20 g) to produce micro-sized vaccine powder formulations (40-60 μm) for epidermal powder immunization (EPI) Methods:A bench-top spray coater was used to spray two vaccines, diphtheria toxoid (dT) and alum-adsorbed hepatitis-B surface antigen (Alum-HBsAg), onto crystalline lactose particles of 40-60 μm in diameter. Particle properties such as particle size, surface morphology, and degree of particle agglomeration were determined. Protein stability was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The immunogenicity of the vaccine was evaluated in vivoby needle injection and epidermal powder immunization (EPI) of mice or guinea pigs. Results:Coating feasibility was demonstrated for both vaccine formulations containing different excipients. However, the nature of the vaccine antigen appeared to affect coating feasibility in terms of particle agglomeration considerably. Delivery of spray-coated dT and alum-HBsAg through EPI to mice and guinea pigs, respectively, generated significant antibody responses, at a level comparable to liquid formulation delivered subcutaneously through needle/syringe injection. Conclusions:The new spray-coating process represents an important technical advance and may provide a useful tool for developing high-valued biopharmaceutical powder formulations for novel applications. The strong in vivoperformance of the coated dT and alum-HBsAg powders by EPI further demonstrated that spray-coating is a viable dry powder formulation process and the skin's epidermal layer presents an efficient vaccine delivery route.
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- 2004
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18. Optimization of an Alum-Adsorbed Vaccine Powder Formulation for Epidermal Powder Immunization
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Maa, Yuh-Fun, Shu, Cassandra, Ameri, Mahmoud, Zuleger, Cindy, Che, Jenny, Osorio, Jorge, Payne, Lendon, and Chen, Dexiang
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Purpose. To develop stable and effective aluminum salt (alum)-adsorbed vaccine powder formulations for epidermal powder immunization (EPI) via a spray freeze-drying (SFD) process. Methods. Powder properties were determined using particle size analysis, tap density, and scanning electron microscopy. Alum coagulation was monitored via optical microscopy and particle sedimentation. Protein analysis was determined by the BCA protein assay, SDS-PAGE, and an enzyme immunoassay. In vivoimmunogenicity and skin reactogenicity were performed on hairless guinea pigs and pigs, respectively. Results. SFD of hepatitis B surface antigen (HBsAg) adsorbed to aluminum hydroxide or aluminum phosphate using an excipient combination of trehalose/mannitol/dextran produced vaccine powders of dense particles and satisfactory powder flowability and hygroscopicity. This formulation also offered excellent long-term stability to the powder and the antigen. The two most important factors influencing alum particle coagulation are the freezing rate and the concentration of aluminum in the liquid formulation for SFD. The SFD vaccines, when delivered to hairless guinea pigs by EPI or injected intramuscularly after reconstitution, were as immunogenic as the original liquid vaccine. A further study showed that EPI with SFD alum-adsorbed diphtheria-tetanus toxoid vaccine was well tolerated, whereas needle injection of the liquid formulation caused persistent granuloma. Conclusions. Stabilization of alum-adsorbed vaccine by SFD has important implications in extending vaccination to areas lacking a cold chain for transportation and storage and may also accelerate the development of new immunization technologies such as EPI.
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- 2003
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19. Stabilization of alum-adjuvanted vaccine dry powder formulations: Mechanism and application
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Maa, Yuh-Fun, Zhao, Lu, Payne, Lendon G., and Chen, Dexiang
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Studies were performed to elucidate the mechanism of alum gel coagulation upon freezing and drying and its relationship to vaccine potency loss and to develop a novel freeze-drying process for the production of stable alum-adjuvanted vaccine formulations suitable for conventional needle injection and epidermal powder immunization (EPI). The alum hydroxide-adjuvanted hepatitis-B surface antigen (Alum-HBsAg) and the alum phosphate-adjuvanted diphtheria and tetanus toxoids (Alum-DT) were dehydrated by freeze drying (FD), spray drying (SD), air drying (AD), or spray freeze drying (SFD). After drying by FD, SD, or AD, alum gels coagulated when examined by optical microscopy and particle size analysis. In addition, desorption of antigen molecules from the coagulated when examined by optical microscopy and particle size analysis. In addition, desorption of antigen molecules from the coagulated alum gel upon reconstitution appeared to be difficult, as indicated by attenuated band intensity on SDS-PAGE. In contrast, SFD alum gels turned a homogenous suspension upon reconstitution, suggesting minimal alum coagulation. In the mouse model, the in vivo immunogenicity of SFD Alum-HBsAg was preserved, whereas the FD Alum-HBsAg suffered significant immunogenicity loss. Grinding of coagulated FD Alum-HBsAg into smaller particles could partially recover the immunogenicity. In a guinea pig study using EPI, the SD Alum-DT formulation was not immunogenic, but the SFD Alum-DT formulations had a vaccine potency comparable to that of the untreated DT administered by I.M. injection. Overall, the relationship of coagulation of alum gel upon reconstitution and the loss of vaccine potency was established in this study. Alum gels became highly coagulated after dehydration by spray drying and traditional freeze-drying processes. However, freezing rate played a critical role in preserving the adjuvant effect of alum and fast freezing decreased the tendency of alum coagulation. Spraying the alum gel into liquid nitrogen represents the fastest freezing rate achievable and resulted in no discernible alum coagulation. Therefore, SFD presents a novel and effective drying process for alum-adjuvanted vaccine formulations and is particularly valuable for dry powder applications such as EPI. © 2003 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 92:319332, 2003
- Published
- 2003
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20. Stabilization of Alum-Adjuvanted Vaccine Dry Powder Formulations: Mechanism and Application
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Maa, Yuh-Fun, Zhao, Lu., Payne, Lendon G., and Chen, Dexiang
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Studies were performed to elucidate the mechanism of alum gel coagulation upon freezing and drying and its relationship to vaccine potency loss and to develop a novel freeze-drying process for the production of stable alum-adjuvanted vaccine formulations suitable for conventional needle injection and epidermal powder immunization (EPI). The alum hydroxide-adjuvanted hepatitis-B surface antigen (Alum-HBsAg) and the alum phosphate-adjuvanted diphtheria and tetanus toxoids (Alum-DT) were dehydrated by freeze drying (FD), spray drying (SD), air drying (AD), or spray freeze drying (SFD). After drying by FD, SD, or AD, alum gels coagulated when examined by optical microscopy and particle size analysis. In addition, desorption of antigen molecules from the coagulated when examined by optical microscopy and particle size analysis. In addition, desorption of antigen molecules from the coagulated alum gel upon reconstitution appeared to be difficult, as indicated by attenuated band intensity on SDS-PAGE. In contrast, SFD alum gels turned a homogenous suspension upon reconstitution, suggesting minimal alum coagulation. In the mouse model, the in vivoimmunogenicity of SFD Alum-HBsAg was preserved, whereas the FD Alum-HBsAg suffered significant immunogenicity loss. Grinding of coagulated FD Alum-HBsAg into smaller particles could partially recover the immunogenicity. In a guinea pig study using EPI, the SD Alum-DT formulation was not immunogenic, but the SFD Alum-DT formulations had a vaccine potency comparable to that of the untreated DT administered by I.M. injection. Overall, the relationship of coagulation of alum gel upon reconstitution and the loss of vaccine potency was established in this study. Alum gels became highly coagulated after dehydration by spray drying and traditional freeze-drying processes. However, freezing rate played a critical role in preserving the adjuvant effect of alum and fast freezing decreased the tendency of alum coagulation. Spraying the alum gel into liquid nitrogen represents the fastest freezing rate achievable and resulted in no discernible alum coagulation. Therefore, SFD presents a novel and effective drying process for alum-adjuvanted vaccine formulations and is particularly valuable for dry powder applications such as EPI.
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- 2003
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21. Needle-free epidermal powder immunization
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Chen, Dexiang, Maa, Yuh-Fun, and Haynes, Joel R
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Due to the presence of a network of antigen-presenting cells and other cells with innate and adaptive immune functions, the skin is both a sensitive immune organ and a practical target site for vaccine administration. A handful of needle-free immunization technologies have emerged in recent years that aim to take advantage of these characteristics. Skin delivery technologies provide potentially safer alternatives to needle injection and promises increased efficacy in the prevention and/or therapy of infectious diseases, allergic disorders and cancer. In this review, we will cover advances in needle-free skin vaccination technologies and their potential applications to disease prevention and therapy. Emphasis will be placed on epidermal powder immunization and particle-mediated (‘gene gun’) DNA immunization, which use similar mechanical devices to deliver protein and DNA vaccines, respectively, into the viable epidermis.
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- 2002
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22. Targeting epidermal Langerhans cells by epidermal powder immunization
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CHEN, Dexiang and PAYNE, Lendon G
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ABSTRACTImmune reactions to foreign or self-antigens lead to protective immunity and, sometimes, immune disorders such as allergies and autoimmune diseases. Antigen presenting cells (APC) including epidermal Langerhans cells (LCs) play an important role in the course and outcome of the immune reactions. Epidermal powder immunization (EPI) is a technology that offers a tool to manipulate the LCs and the potential to harness the immune reactions towards prevention and treatment of infectious diseases and immune disorders.
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- 2002
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23. Targeting epidermal Langerhans cells by epidermal powder immunization
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CHEN, Dexiang and PAYNE, Lendon G
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ABSTRACTImmune reactions to foreign or self-antigens lead to protective immunity and, sometimes, immune disorders such as allergies and autoimmune diseases. Antigen presenting cells (APC) including epidermal Langerhans cells (LCs) play an important role in the course and outcome of the immune reactions. Epidermal powder immunization (EPI) is a technology that offers a tool to manipulate the LCs and the potential to harness the immune reactions towards prevention and treatment of infectious diseases and immune disorders.Cell Research (2002) 12, 97–104. doi:10.1038/sj.cr.7290115
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- 2002
24. Epidermal Powder Immunization Induces both Cytotoxic T-Lymphocyte and Antibody Responses to Protein Antigens of Influenza and Hepatitis B Viruses
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Chen, Dexiang, Weis, Kathleen F., Chu, Qili, Erickson, Cherie, Endres, Ryan, Lively, Chris R., Osorio, Jorge, and Payne, Lendon G.
- Abstract
ABSTRACTCytotoxic T lymphocytes (CTL) play a vital role in host defense against viral and intracellular bacterial infections. However, nonreplicating vaccines administered by intramuscular injection using a syringe and needle elicit predominantly humoral responses and not CTL responses. Here we report that epidermal powder immunization (EPI), a technology that delivers antigens on 1.5- to 2.5-µm gold particles to the epidermis using a needle-free powder delivery system, elicits CTL responses to nonreplicating antigens. Following EPI, a majority of the antigen-coated gold particles were found in the viable epidermis in the histological sections of the target skin. Further studies using transmission electron microscopy revealed the intracellular localization of the gold particles. Many Langerhans cells (LCs) at the vaccination site contained antigen-coated particles, as revealed by two-color immunofluorescence microscopy, and these cells were found in the draining lymph nodes 20 h later. Immune responses to several viral protein antigens after EPI were studied in mice. EPI with hepatitis B surface antigen (HBsAg) and a synthetic peptide of influenza virus nucleoprotein (NP peptide) elicited antigen-specific CTL responses as well as antibody responses. In an in vitro cell depletion experiment, we demonstrated that the CTL activity against HBsAg elicited by EPI was attributed to CD8+, not CD4+, T cells. As controls, needle injections of HBsAg or the NP peptide into deeper tissues elicited solely antibody, not CTL, responses. We further demonstrated that EPI with inactivated A/Aichi/68 (H3N2) or A/Sydney/97 (H3N2) influenza virus elicited complete protection against a mouse-adapted A/Aichi/68 virus. In summary, EPI directly delivers protein antigens to the cytosol of the LCs in the skin and elicits both cellular and antibody responses.
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- 2001
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25. Serum and Mucosal Immune Responses to an Inactivated Influenza Virus Vaccine Induced by Epidermal Powder Immunization
- Author
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Chen, Dexiang, Periwal, Sangeeta B., Larrivee, Katherine, Zuleger, Cindy, Erickson, Cherie A., Endres, Ryan L., and Payne, Lendon G.
- Abstract
ABSTRACTBoth circulating and mucosal antibodies are considered important for protection against infection by influenza virus in humans and animals. However, current inactivated vaccines administered by intramuscular injection using a syringe and needle elicit primarily circulating antibodies. In this study, we report that epidermal powder immunization (EPI) via a unique powder delivery system elicits both serum and mucosal antibodies to an inactivated influenza virus vaccine. Serum antibody responses to influenza vaccine following EPI were enhanced by codelivery of cholera toxin (CT), a synthetic oligodeoxynucleotide containing immunostimulatory CpG motifs (CpG DNA), or the combination of these two adjuvants. In addition, secretory immunoglobulin A (sIgA) antibodies were detected in the saliva and mucosal lavages of the small intestine, trachea, and vaginal tract, although the titers were much lower than the IgG titers. The local origin of the sIgA antibodies was further shown by measuring antibodies released from cultured tracheal and small intestinal fragments and by detecting antigen-specific IgA-secreting cells in the lamina propria using ELISPOT assays. EPI with a single dose of influenza vaccine containing CT or CT and CpG DNA conferred complete protection against lethal challenges with an influenza virus isolated 30 years ago, whereas a prime and boost immunizations were required for protection in the absence of an adjuvant. The ability to elicit augmented circulating antibody and mucosal antibody responses makes EPI a promising alternative to needle injection for administering vaccines against influenza and other diseases.
- Published
- 2001
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26. The Levels and Bactericidal Capacity of Antibodies Directed against the UspA1 and UspA2 Outer Membrane Proteins ofMoraxella(Branhamella) catarrhalisin Adults and Children
- Author
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Chen, Dexiang, Barniak, Vicki, VanDerMeid, Karl R., and McMichael, John C.
- Abstract
ABSTRACTThe UspA1 and UspA2 proteins from Moraxella catarrhalisshare antigenic epitopes and are promising vaccine candidates. In this study, the levels and bactericidal activities of antibodies in sera from healthy adults and children toward UspA1 and UspA2 from the O35E strain were measured. Human sera contained antibodies to both proteins, and the levels of immunoglobulin G (IgG) antibodies were age dependent. Adult sera had significantly higher titers of IgG than child sera (P< 0.01). The IgG3 titers to the UspA proteins were higher than the IgG1 titers in the adults’ sera, while the IgG1 titers were higher than the IgG3 titers in the children’s sera (P< 0.05). The IgG antibodies in the sera from 2-month-old children appeared to be maternally derived, since the mean titer was significantly higher than that in sera from 6- to 7-month-old children (P< 0.05). Serum IgA antibodies to both UspA1 and UspA2 were low during the first 7 months of age but thereafter gradually increased along with the IgG titers. Analysis of sera absorbed with UspA1 or UspA2 showed that the antibodies to UspA1 and UspA2 were cross-reactive with each other and associated with serum bactericidal activity. Examination of affinity-purified human antibodies confirmed that naturally acquired antibodies to UspA1 and UspA2 were bactericidal and cross-reactive. These results support using UspA1 and UspA2 in a vaccine to prevent M. catarrhalisinfections.
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- 1999
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27. Isolation and Characterization of Two Proteins fromMoraxella catarrhalisThat Bear a Common Epitope
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McMichael, John C., Fiske, Michael J., Fredenburg, Ross A., Chakravarti, Deb N., VanDerMeid, Karl R., Barniak, Vicki, Caplan, Jeffrey, Bortell, Eric, Baker, Steven, Arumugham, Rasappa, and Chen, Dexiang
- Abstract
ABSTRACTThe UspA1 and UspA2 proteins of Moraxella catarrhalisare potential vaccine candidates for preventing disease caused by this organism. We have characterized both proteins and evaluated their vaccine potential using both in vitro and in vivo assays. Both proteins were purified from the O35E isolate by Triton X-100 extraction, followed by ion-exchange and hydroxyapatite chromatography. Analysis of the sequences of internal peptides, prepared by enzymatic and chemical cleavage of the proteins, revealed that UspA1 and UspA2 exhibited distinct structural differences but shared a common sequence including an epitope recognized by the monoclonal antibody 17C7. By sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), purified UspA1 exhibited a molecular weight of approximately 350,000 when unheated and a molecular weight of 100,000 after being heated for 10 min at 100°C. In contrast, purified UspA2 exhibited an apparent molecular weight of 240,000 by SDS-PAGE that did not change with the length of time of heating. Their sizes as determined by gel filtration were 1,150,000 and 830,000 for UspA1 and UspA2, respectively. Preliminary results indicate the proteins have separate functions in bacterial pathogenesis. Purified UspA1 was found to bind HEp-2 cells, and sera against UspA1, but not against UspA2, blocked binding of the O35E isolate to the HEp-2 cells. UspA1 also bound fibronectin and appears to have a role in bacterial attachment. Purified UspA2, however, did not bind fibronectin but had an affinity for vitronectin. Both proteins elicited bactericidal antibodies in mice to homologous and heterologous disease isolates. Finally, mice immunized with each of the proteins, followed by pulmonary challenge with either the homologous or a heterologous isolate, cleared the bacteria more rapidly than mock-immunized mice. These results suggest that UspA1 and UspA2 serve different virulence functions and that both are promising vaccine candidates.
- Published
- 1998
- Full Text
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