- Immunogenicity and safety of an investigational tetravalent recombinant subunit vaccine for dengue: results of a Phase I randomized clinical trial in flavivirus-Naïve adults. [Journal Article]
- HVHum Vaccin Immunother 2018 Nov 14
- There is an unmet medical need for vaccines to prevent dengue. V180 is an investigational recombinant subunit vaccine that consists of truncated dengue envelope proteins (DEN-80E) for all 4 serotypes...
There is an unmet medical need for vaccines to prevent dengue. V180 is an investigational recombinant subunit vaccine that consists of truncated dengue envelope proteins (DEN-80E) for all 4 serotypes. Three dosage levels of the tetravalent DEN-80E antigens were assessed in a randomized, placebo-controlled, Phase I dose-escalation, first-in-human proof-of-principle trial in healthy, flavivirus-naïve adults in Australia (NCT01477580). The 9 V180 formulations that were assessed included either ISCOMATRIX™ adjuvant (2 dosage levels), aluminum-hydroxide adjuvant, or were unadjuvanted, and were compared to phosphate-buffered saline placebo. Volunteers received 3 injections of assigned product on a 0, 1, 2 month schedule, and were followed for safety through 1 year after the last injection. Antibody levels were assessed at 6 time-points: enrollment, 28 days after each injection, and 6 and 12 months Postdose 3 (PD3). Of the 98 randomized participants, 90 (92%) received all 3 injections; 83 (85%) completed 1-year follow-up. Immunogenicity was measured by a qualified Focus Reduction Neutralization Test with a 50% neutralization cutoff (FRNT50). All 6 V180 formulations with ISCOMATRIX™ adjuvant showed robust immunogenicity, while the 1 aluminum-adjuvanted and 2 unadjuvanted formulations were poorly immunogenic. Geometric mean antibody titers generally declined at 6 months and 1 year PD3. All 9 V180 formulations were generally well tolerated. Formulations with ISCOMATRIX™ adjuvant were associated with more adverse events than aluminum-adjuvanted or unadjuvanted formulations.
- Adjuvants in allergen-specific immunotherapy: modulating and enhancing the immune response. [Review]
- JIJ Investig Allergol Clin Immunol 2018 Nov 12; :0
- Allergen-specific immunotherapy (AIT) is the only treatment that may affect the natural course of allergic diseases such as allergic asthma, allergic rhinitis, and IgEmediated food allergy. Adjuvants...
Allergen-specific immunotherapy (AIT) is the only treatment that may affect the natural course of allergic diseases such as allergic asthma, allergic rhinitis, and IgEmediated food allergy. Adjuvants are used to induce a quicker, more potent, and longer-lasting AIT immune response. Up to now, only four compounds are used as adjuvants in currently marketed AIT products: aluminum hydroxide, calcium phosphate, microcrystalline tyrosine (MCT), and monophosphoryl lipid A (MPL). The three first adjuvants are delivery systems with depot effect, although they also may have immunomodulatory properties. These firstgeneration adjuvants are still widely used, especially aluminum hydroxide. However, aluminum has some limitations. MCT is the depot formulation of L-tyrosine; it enhances IgG production withoutinducing a significant IgE increase, is biodegradable and has good local and systemic tolerability. In turn, MPL is an immunostimulatory agent that is the only second-generation adjuvant currently used for AIT. In addition, there are multiple adjuvants under research, including immunostimulatory sequences (ISS), nanoparticles (liposomes, virus-like particlesand biodegradable polymers), and phosphatidylserine derivatives. In a murine model of allergic bronchial inflammation by sensitization to olive pollen, specific IgE level was significantly higher in sensitized mice treated with olive pollen and aluminum hydroxide. However, sensitized mice treated with olive pollen and bacterial derivatives (MPL or ISS) showed a significant reduction of specific IgE levels and a significant improvement of bronchial hyperreactivity.
- Molecular Signature of Aluminum Hydroxide Adjuvant in Ovine PBMCs by Integrated mRNA and microRNA Transcriptome Sequencing. [Journal Article]
- FIFront Immunol 2018; 9:2406
- There have been few in vivo studies on the effect of aluminum hydroxide adjuvant and its influence on the immune response to vaccination. In this study, lambs received a parallel subcutaneous treatme...
There have been few in vivo studies on the effect of aluminum hydroxide adjuvant and its influence on the immune response to vaccination. In this study, lambs received a parallel subcutaneous treatment with either commercial vaccines containing aluminum hydroxide or an equivalent dose of this compound only with the aim of identifying the activated molecular signature. Blood samples were taken from each animal at the beginning and at the end of the experiment and PBMCs isolated. Total RNA and miRNA libraries were prepared and sequenced. After alignment to the Oar3.1 reference genome and differential expression with 3 programs, gene enrichment modeling was performed. For miRNAs, miRBase and RNAcentral databases were used for detection and characterization. Three expression comparisons were made: vaccinated animals at the beginning and at the end of the treatment, adjuvanted animals at the same times, and animals of both treatments at the end of the experiment. After exposure to both treatments, a total of 2,473; 2,980 and 429 differentially expressed genes were identified in vaccinated animals, adjuvanted animals and animals at the end of both treatments, respectively. In both adjuvant and vaccine treated animals the NF-κB signaling pathway was enriched. On the other hand, it can be observed a downregulation of cytokines and cytokine receptors in the adjuvanted group compared to the vaccinated group at the final time, suggesting a milder induction of the immune response when the adjuvant is alone. As for the miRNA analysis, 95 miRNAs were detected: 64 previously annotated in Ovis aries, 11 annotated in Bos taurus and 20 newly described. Interestingly, 6 miRNAs were differentially expressed in adjuvant treated animals, and 3 and 1 in the other two comparisons. Lastly, an integrated miRNA-mRNA expression profile was developed, in which a miRNA-mediated regulation of genes related to DNA damage stimulus was observed. In brief, it seems that aluminum-containing adjuvants are not simple delivery vehicles for antigens, but also induce endogenous danger signals that can stimulate the immune system. Whether this contributes to long-lasting immune activation or to the overstimulation of the immune system remains to be elucidated.
- Maternal Separation as Early-Life Stress Causes Enhanced Allergic Airway Responses by Inhibiting Respiratory Tolerance in Mice. [Journal Article]
- TJTohoku J Exp Med 2018; 246(3):155-165
- Epidemiologic studies indicate that exposure to psychosocial stress in early childhood is a risk factor of adult-onset asthma, but the mechanisms of this relationship are poorly understood. Therefore...
Epidemiologic studies indicate that exposure to psychosocial stress in early childhood is a risk factor of adult-onset asthma, but the mechanisms of this relationship are poorly understood. Therefore, we examined whether early-life stress increases susceptibility to adult-onset asthma by inhibiting the development of respiratory tolerance. Neonatal BALB/c female mice were aerosolized with ovalbumin (OVA) to induce immune tolerance prior to immune sensitization with an intraperitoneal injection of OVA and the adjuvant aluminum hydroxide. Maternal separation (MS) was applied as an early-life stressor during the induction phase of immune tolerance. The mice were challenged with OVA aerosol in adulthood, and allergic airway responses were evaluated, including airway hyper-responsiveness to inhaled methacholine, inflammatory cell infiltration, bronchoalveolar lavage fluid levels of interleukin (IL)-4, IL-5, and IL-13, and serum OVA-specific IgE. We then evaluated the effects of MS on the development of regulatory T (Treg) cells in bronchial lymph nodes (BLN) and on splenocyte proliferation and cytokine expression. In mice that underwent MS and OVA tolerization, the allergic airway responses and OVA-induced proliferation and IL-4 expression of splenocytes were significantly enhanced. Furthermore, exposure to MS was associated with a lower number of Treg cells in the BLN. These findings suggest that exposure to early-life stress prevents the acquisition of respiratory tolerance to inhaled antigen due to insufficient Treg cell development, resulting in Th2-biased sensitization and asthma onset. We provide the evidence for inhibitory effects of early-life stress on immune tolerance. The present findings may help to clarify the pathogenesis of adult-onset asthma.
- Coupled Multimodal Dynamics of Hydrogen-Containing Ion Networks in Water-Deficient, Sodium-Hydroxide-Aluminate Solutions. [Journal Article]
- JPJ Phys Chem B 2018 Nov 08
- The (meta)stability of low water activity, sodium hydroxide/aluminate (Na+OH-/Al(OH)4-) electrolytes dictates kinetics in the Bayer process for aluminum refining and high-level nuclear waste processi...
The (meta)stability of low water activity, sodium hydroxide/aluminate (Na+OH-/Al(OH)4-) electrolytes dictates kinetics in the Bayer process for aluminum refining and high-level nuclear waste processing. We utilized quasi-elastic neutron scattering (QENS) and proton nuclear magnetic resonance spectroscopy (1H NMR) to investigate the picosecond (ps) to microsecond (ms) timescale motions of H-bearing species (Al(OH)4- monomers/clusters, OH- and H2O) in extremely concentrated sodium aluminate solutions. In the QENS data, in contrast to typical liquids, no short-time translational diffusion was observed at 293 K, but two types of localized motions were found: (i) local backbone tumbling or a formation of large hydrated ion clusters on the order of 40-60 ps; and (ii) much slower, complex, collective dynamics of the ensemble of H-bearing species on the order of 350-750 ps. Variable temperature, pulsed field gradient, diffusion ordered 1H NMR was used to determine the ensemble translational motion along with relaxometry to calculate rotational correlation coefficients. The ensemble rotational correlation times were on the order of 184-300 ps from 1H NMR, which is consistent with the timescale of the QENS components. Complementary molecular dynamics simulation of NaOH solutions exhibit extensive ion-networks potentially responsible for the observed dynamical coupling of water with the motion of large hydrated ion clusters. Understanding these collective motions will aid in predicting the behavior of complex solutions during aluminum production and during nuclear waste processing.
- OK-432 Acts as Adjuvant to Modulate T Helper 2 Inflammatory Responses in a Murine Model of Asthma. [Journal Article]
- JIJ Immunol Res 2018; 2018:1697276
- Enhanced type 2 helper T (Th2) cell responses to inhaled harmless allergens are strongly associated with the development of allergic diseases. Antigen formulated with an appropriate adjuvant can elic...
Enhanced type 2 helper T (Th2) cell responses to inhaled harmless allergens are strongly associated with the development of allergic diseases. Antigen formulated with an appropriate adjuvant can elicit suitable systemic immunity to protect individuals from disease. Although much has been learned about Th1-favored immunomodulation of OK-432, a streptococcal preparation with antineoplastic activity, little is known about its adjuvant effect for allergic diseases. Herein, we demonstrate that OK-432 acts as an adjuvant to favor a systemic Th1 polarization with an elevation in interferon- (IFN-) γ and ovalbumin- (OVA-) immunoglobulin (Ig) G2a. Prior vaccination with OK-432 formulated against OVA attenuated lung eosinophilic inflammation and Th2 cytokine responses that were caused by challenging with OVA through the airway. This vaccination with OK-432 augmented the ratios of IFN-γ/interleukin- (IL-) 4 cytokine and IgG2a/IgG1 antibody compared to the formulation with Th2 adjuvant aluminum hydroxide (Alum) or antigen only. The results obtained in this study lead us to propose a potential novel adjuvant for clinical use such as prophylactic vaccination for pathogens and immunotherapy in atopic diseases.
- The protective effects of nasal PcrV-CpG oligonucleotide vaccination against Pseudomonas aeruginosa pneumonia. [Journal Article]
- MIMicrobiol Immunol 2018 Oct 31
- An effective vaccine against Pseudomonas aeruginosa would be hugely beneficial to people who are susceptible to the serious infections it causes. Vaccination against PcrV of the P. aeruginosa type II...
An effective vaccine against Pseudomonas aeruginosa would be hugely beneficial to people who are susceptible to the serious infections it causes. Vaccination against PcrV of the P. aeruginosa type III secretion system is a potential prophylactic strategy for improving the incidence and poor prognosis of P. aeruginosa pneumonia. Here, the effect of nasal PcrV adjuvanted with CpG oligodeoxynucleotide (CpG) was compared with a nasal PcrV/aluminum hydroxide gel (alum) vaccine. Seven mouse groups in the infection series were vaccinated intranasally with one of the following: 1, PcrV-CpG; 2, PcrV-alum; 3, PcrV alone; 4, CpG alone; 5, alum alone; 6 and 7, a saline control. Fifty days after the first immunization, anti-PcrV IgG, IgA and IgG isotype titers were measured, and significant increases in these parameters were detected in the PcrV-CpG vaccinated mice only. The vaccinated mice were then intratracheally infected with a lethal dose of P. aeruginosa and their body temperatures and survival were monitored for 24 h, with edema, bacteria, myeloperoxidase activity and lung histology being evaluated at 24 h post-infection. Consequently, 73% of the PcrV-CpG-vaccinated mice survived, but less than 30% of the mice vaccinated with PcrV-alum or adjuvant alone survived. Lung edema and other inflammatory parameters were less severe in the PcrV-CpG group. The significant increase in PcrV-specific IgA titers detected following PcrV-CpG vaccination probably comprise part of the disease protection mechanism. Overall, our data show that intranasal PcrV-CpG vaccination has potential efficacy for clinical application against P. aeruginosa pneumonia.
- Solvent-free hydrothermal synthesis of gamma-aluminum oxide nanoparticles with selective adsorption of Congo red. [Journal Article]
- JCJ Colloid Interface Sci 2018 Oct 19; 536:180-188
- Aluminum hydroxide and oxide have been widely used for decontamination due to their environmentally friendly nature and cost effectiveness. Aluminum (hydro) oxides are the main phases of aluminum-der...
Aluminum hydroxide and oxide have been widely used for decontamination due to their environmentally friendly nature and cost effectiveness. Aluminum (hydro) oxides are the main phases of aluminum-derived environment materials. Herein, the solvent-free hydrothermal synthesis of gamma-aluminum oxide (γ-Al2O3) nanoparticles and phase transformation of AlOOH into γ-Al2O3 are reported. Hydrothermal treatment of NH3·H2O-induced aluminum precipitate resulted in the formation of AlOOH, which was an intermediate product of γ-Al2O3. AlOOH was transformed into highly crystalline 20-nm γ-Al2O3 particles through calcination at 500 °C due to dehydration. The transformation was confirmed through X-ray diffraction (XRD) and thermogravimetric (TG) analyses. The resulting γ-Al2O3 had superior adsorption ability for the anionic Congo red (CR) dye than for the cationic methylene blue (MB) and malachite green (MG) dyes. The selective adsorption ability of CR instead of MB was attributed to the electrostatic attraction and hydrogen bonds between the amino group and azo double bond of CR, and between the amino group and hydroxyl group in γ-Al2O3. Thus, this study investigated crystalline phase transformation into γ-Al2O3 and selective adsorption capacity of CR, which provides important information regarding the synthesis of crystalline γ-Al2O3 adsorbent, with selective adsorption ability for decontamination applications.
- Reduction of Fluoride in Water Phase by Micro-Nano Bubble Pretreatment Process. [Journal Article]
- JNJ Nanosci Nanotechnol 2019 Feb 01; 19(2):1155-1157
- Fluoride is important to aquatic environment and health aspects, and the optimal fluoride concentration in water is below 1 mg/L. In this study, the micro-nano bubble pretreatment was applied to remo...
Fluoride is important to aquatic environment and health aspects, and the optimal fluoride concentration in water is below 1 mg/L. In this study, the micro-nano bubble pretreatment was applied to remove fluoride ions in the water phase. The pH control by calcium hydroxide (Ca(OH)₂), and coagulation processes with poly aluminum chloride (PAC), aluminum sulfate (Alum), F900 and two kinds of polymer named as A-polymer and A430P polymer were applied for the pretreated wastewater. In results, the combination of PAC and A430P polymer with micro-nano bubble pretreated wastewater showed a higher fluoride removal than the case of other combinations. In chemical oxygen demand (COD) removal, the combination of Alum and A430P polymer with micro-nano bubble pretreated wastewater showed the best removal efficiency (64.6%) while the COD removal without pretreatment was 71.4% for fluoride and 57.2% for COD.
New Search Next
- [Effects of sIL-13Rα2 on the nasal mucosa goblet cell apoptosis of allergic rhinitis of rats]. [Journal Article]
- ZEZhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2018 Oct 07; 53(10):745-750
- Objective: To investigate the effects of sIL-13Rα2 on the apoptosis of goblet cell in nasal mucosa of allergic rhinitis rats. Methods: Forty healthy male Wistar rats were randomly divided into 4 gr...
Objective: To investigate the effects of sIL-13Rα2 on the apoptosis of goblet cell in nasal mucosa of allergic rhinitis rats. Methods: Forty healthy male Wistar rats were randomly divided into 4 groups (10 rats per group): control group (group A), AR group (group B), sIL-13Rα2 group (group C) and triamcinolone acetonide group (group D). Ovalbumin (OVA) and aluminum hydroxide were used to establish the AR rat model. After the establishment of AR rat models, 50 μl PBS, 100 μg/50 μl IL-13Rα2 and 3.5 μg/50 μl triamcinolone acetonide were respectively dropped into each nasal cavity of every rat two times a week from 4 to 10 week in group B, group C and group D. Group A was operated with saline instead of OVA. The nasal mucosa tissues were collected at 24 h after the final administration. AB-PAS staining method was used to detect the quantity and secretion of goblet cells in the nasal mucosa tissue of all groups. Immunohistochemistry method was used to detect the expression of Bax proteins.Apoptosis was detected by TUNEL method.ANOVA analysis was used to compare multiple groups, and LSD-t test was used to compare the two groups.Pearson correlation analysis was used to analyze the correlation between the Bax positive cell rate of goblet cells and the rate of apoptotic cells. The difference was statistically significant with P<0.05. Results: Compared with group A, there were more goblet cells and hypersecretion of mucus in the nasal mucosa tissue of rats in group B while fewer in group C. The goblet cells in group C and group D were significantly fewer than that in group B (0.639 00±0.831 vs 0.956 7±0.980, 0.661 90±0.657 vs 0.956 7±0.980, t value was 2.748, 2.767, respectively, all P<0.05). The immunohistochemistry results showed that the positive expression rates of Bax protein in goblet cells of group C and group D were significantly higher than that in group B (0.880 2±0.125 vs 0.568 7±0.953, 0.938 4±0.200 vs 0.568 7±0.953, t value was -2.292, -2.685, respectively, all P<0.05). The apoptosis rates of goblet cell in nasal mucosa of group C and group D were also significantly higher than that in group B (0.516 0±0.079 vs 0.274 0±0.056, 0.535 4±0.829 vs 0.274 0±0.056, t value was -17.671, -2.225, respectively, all P<0.05). The expression of Bax protein and apoptosis of goblet cells were positively correlated (r=0.859, P<0.01). Conclusion: sIL-13Rα2 can induce apoptosis of the goblet cells in nasal mucosa of allergic rhinitis rats, by inhibiting IL-13 and up regulating Bax.