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The Lancet. Infectious Diseases Nov 2023Malaria transmission-blocking vaccines target mosquito-stage parasites and will support elimination programmes. Gamete vaccine Pfs230D1-EPA/Alhydrogel induced superior... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Malaria transmission-blocking vaccines target mosquito-stage parasites and will support elimination programmes. Gamete vaccine Pfs230D1-EPA/Alhydrogel induced superior activity to zygote vaccine Pfs25-EPA/Alhydrogel in malaria-naive US adults. Here, we compared these vaccines in malaria-experienced Malians.
METHODS
We did a pilot safety study then double-blind, block-randomised, comparator-controlled main-phase trial in malaria-intense Bancoumana, Mali. 18-50-year-old healthy non-pregnant, non-breastfeeding consenting adult residents were randomly assigned (1:1:1:1) to receive four doses at months 0, 1, 4·5, and 16·5 of either 47 μg Pfs25, 40 μg Pfs230D1 or comparator (Twinrix or Menactra)-all co-administered with normal saline for blinding-or 47 μg Pfs25 plus 40 μg Pfs230D1 co-administered. We documented safety and tolerability (primary endpoint in the as-treated populations) and immunogenicity (secondary endpoint in the as-treated populations: ELISA, standard-membrane-feeding assay, and mosquito direct skin feed assay). This trial is registered at ClinicalTrials.gov, NCT02334462.
FINDINGS
Between March 19, and June 2, 2015, we screened 471 individuals. Of 225 enrolled for the pilot and main cohorts, we randomly assigned 25 participants to pilot safety cohort groups of five (20%) to receive a two-dose series of Pfs25-EPA/Alhydrogel (16 μg), Pfs230D1-EPA/Alhydrogel (15 μg) or comparator, followed by Pfs25-EPA/Alhydrogel (16 μg) plus Pfs230D1-EPA/Alhydrogel (15 μg) or comparator plus saline. For the main cohort, we enrolled 200 participants between May 11 and June 2, 2015, to receive a four-dose series of 47 μg Pfs25-EPA/Alhydrogel plus saline (n=50 [25%]; Pfs25), 40 μg Pfs230D1-EPA/Alhydrogel plus saline (n=49 [25%]; Pfs230D1), 47 μg Pfs25-EPA/Alhydrogel plus 40 μg Pfs230D1-EPA/Alhydrogel (n=50 [25%]; Pfs25 plus Pfs230D1), or comparator (Twinrix or Menactra) plus saline (n=51 [25%]). Vaccinations were well tolerated in the pilot safety and main phases. Most vaccinees became seropositive after two Pfs230D1 or three Pfs25 doses; peak titres increased with each dose thereafter (Pfs230D1 geometric mean: 77·8 [95% CI 56·9-106·3], 146·4 [108·3-198·0], and 410·2 [301·6-558·0]; Pfs25 geometric mean 177·7 [130·3-242·4] and 315·7 [209·9-474·6]). Functional activity (mean peak transmission-reducing activity) appeared for Pfs230D1 (74·5% [66·6-82·5]) and Pfs25 plus Pfs230D1 (68·6% [57·3-79·8]), after the third dose and after the fourth dose (88·9% [81·7-96·2] for Pfs230D1 and 85·0% [78·4-91·5] Pfs25 plus Pfs230D1) but not for Pfs25 (58·2% [49·1-67·3] after the third dose and 58·2% [48·5-67·9] after the fourth dose). Pfs230D1 transmission-reducing activity (73·7% [64·1-83·3]) persisted 10 weeks after the fourth dose. Transmission-reducing activity of 80% was estimated at 1659 ELISA units for Pfs25, 218 for Pfs230D1, and 223 for Pfs230D1 plus Pfs25. After 3850 direct skin feed assays, 35 participants (12 Pfs25, eight Pfs230D1, five Pfs25 plus Pfs230D1, and ten comparator) had transmitted parasites at least once. The proportion of positive assays in vaccine groups (Pfs25 33 [3%] of 982 [-0·013 to 0·014], Pfs230D1 22 [2%] of 954 [-0·005 to 0·027], and combination 11 [1%] of 940 [-0·024 to 0·002]) did not differ from that of the comparator (22 [2%] of 974), nor did Pfs230D1 and combination groups differ (-0·024 to 0·001).
INTERPRETATION
Pfs230D1 but not Pfs25 vaccine induces durable serum functional activity in Malian adults. Direct skin feed assays detect parasite transmission to mosquitoes but increased event rates are needed to assess vaccine effectiveness.
FUNDING
Intramural Research Program of the National Institute of Allergy and Infectious Diseases and US National Institutes of Health.
Topics: Animals; Adult; Humans; Adolescent; Young Adult; Middle Aged; Aluminum Hydroxide; Malaria, Falciparum; Plasmodium falciparum; Malaria Vaccines; Meningococcal Vaccines; Double-Blind Method; Immunogenicity, Vaccine
PubMed: 37499679
DOI: 10.1016/S1473-3099(23)00276-1 -
Vaccine Sep 2023The ongoing evolution and emergence of SARS-CoV-2 variants have raised concerns regarding the efficacy of existing vaccines and therapeutic agents. This study aimed to...
The ongoing evolution and emergence of SARS-CoV-2 variants have raised concerns regarding the efficacy of existing vaccines and therapeutic agents. This study aimed to investigate the immunogenicity of an aluminum hydroxide (Alum) and CpG adjuvanted inactivated vaccine (IAV) candidate against SARS-CoV-2 in mice. A comparison was made between the immune response of mice vaccinated with the Alum+CpG adjuvant IAV and those vaccinated with the Alum adjuvant IAV. Mice immunized with Alum+CpG adjuvant IAV demonstrated high antibody titers and a durable humoral immune response, as well as a Th1-type cellular immune response. Notably, compared to Alum alone vaccine, the Alum+CpG adjuvant IAV induced significantly higher proportions of GC B cells in the splenocytes of immunized mice. Importantly, the changes in inflammatory cytokine levels in the sera of mice vaccinated with the Alum+CpG adjuvant IAV followed a similar trend to that of the Alum adjuvant IAV, which had been proven safe in clinical trials. Overall, our results demonstrate that Alum+CpG adjuvant has the potential to serve as a novel adjuvant, thereby providing valuable insights into the development of vaccine formulations.
Topics: Animals; Mice; Aluminum Hydroxide; COVID-19; SARS-CoV-2; Adjuvants, Immunologic
PubMed: 37640568
DOI: 10.1016/j.vaccine.2023.08.061 -
Toxics Jan 2024The recovery and recycling of metals that generate toxic ions in the environment is of particular importance, especially when these are tungsten and, in particular,...
The recovery and recycling of metals that generate toxic ions in the environment is of particular importance, especially when these are tungsten and, in particular, thorium. The radioactive element thorium has unexpectedly accessible domestic applications (filaments of light bulbs and electronic tubes, welding electrodes, and working alloys containing aluminum and magnesium), which lead to its appearance in electrical and electronic waste from municipal waste management platforms. The current paper proposes the simultaneous recovery of waste containing tungsten and thorium from welding electrodes. Simultaneous recovery is achieved by applying a hybrid membrane electrolysis technology coupled with nanofiltration. An electrolysis cell with sulphonated polyether-ether-ketone membranes (sPEEK) and a nanofiltration module with chitosan-polypropylene membranes (C-PHF-M) are used to carry out the hybrid process. The analysis of welding electrodes led to a composition of W (tungsten) 89.4%; Th 7.1%; O 2.5%; and Al 1.1%. Thus, the parameters of the electrolysis process were chosen according to the speciation of the three metals suggested by the superimposed Pourbaix diagrams. At a constant potential of 20.0 V and an electrolysis current of 1.0 A, the pH is varied and the possible composition of the solution in the anodic workspace is analyzed. Favorable conditions for both electrolysis and nanofiltration were obtained at pH from 6 to 9, when the soluble tungstate ion, the aluminum hydroxide, and solid thorium dioxide were formed. Through the first nanofiltration, the tungstate ion is obtained in the permeate, and thorium dioxide and aluminum hydroxide in the concentrate. By adding a pH 13 solution over the two precipitates, the aluminum is solubilized as sodium aluminate, which will be found after the second nanofiltration in the permeate, with the thorium dioxide remaining integrally (within an error of ±0.1 ppm) on the C-PHF-M membrane.
PubMed: 38393198
DOI: 10.3390/toxics12020103 -
Polymers Aug 2023This study investigates the influence of silane-treated aluminum hydroxide on the mechanical performance of flame-retardant composites. These composites have potential...
This study investigates the influence of silane-treated aluminum hydroxide on the mechanical performance of flame-retardant composites. These composites have potential applications for luggage bags, as a replacement for conventional plastics, offering more durability and lighter weight. Glass fabric was used as the reinforcement, while epoxy was used as the matrix material. To impart flame retardancy, aluminum hydroxide nanoparticles were used as fillers in different weight % age (5%, 10% and 15%). As these are inorganic particles and have compatibility issues with the matrix material, silane-coupling agents (Dynasylan 6490 and Dynasylan Glymo) were used to treat these filler particles. Both the silane-coupling agents fraction used for treatment and the fillers fraction added to the composites were varied to determine the most optimum combination. The mechanical properties of the developed composites such as tensile, flexural, and short beam shear strength were investigated. The best results were exhibited by 10% aluminum hydroxide fillers treated with 1% (by weight) coupling agent (Dynasylan Glymo).
PubMed: 37688139
DOI: 10.3390/polym15173514 -
Human Vaccines & Immunotherapeutics Dec 2023COVID-19 pandemic caused by SARS-CoV-2 infection has an impact on global public health and social economy. The emerging immune escape of SARS-CoV-2 variants pose great...
COVID-19 pandemic caused by SARS-CoV-2 infection has an impact on global public health and social economy. The emerging immune escape of SARS-CoV-2 variants pose great challenges to the development of vaccines based on original strains. The development of second-generation COVID-19 vaccines to induce immune responses with broad-spectrum protective effects is a matter of great urgency. Here, a prefusion-stabilized spike (S) trimer protein based on B.1.351 variant was expressed and prepared with CpG7909/aluminum hydroxide dual adjuvant to investigate the immunogenicity in mice. The results showed that the candidate vaccine could induce a significant receptor binding domain-specific antibody response and a substantial interferon-γ-mediated immune response. Furthermore, the candidate vaccine also elicited robust cross-neutralization against the pseudoviruses of the original strain, Beta variant, Delta variant and Omicron variant. The vaccine strategy of S-trimer protein formulated with CpG7909/aluminum hydroxide dual adjuvant may be considered a means to increase vaccine effectiveness against future variants.
Topics: Animals; Humans; Mice; COVID-19 Vaccines; SARS-CoV-2; COVID-19; Aluminum Hydroxide; Pandemics; Adjuvants, Immunologic; Antibodies, Neutralizing; Spike Glycoprotein, Coronavirus; Antibodies, Viral
PubMed: 36882925
DOI: 10.1080/21645515.2023.2186110 -
Polymers Nov 2023Particle boards are manufactured through a hot pressing process using wood materials (natural polymer materials) and adhesive, which find common usage in indoor...
Analyzing Temperature Distribution Patterns on the Facing and Backside Surface: Investigating Combustion Performance of Flame-Retardant Particle Boards Using Aluminum Hypophosphite, Intumescent, and Magnesium Hydroxide Flame Retardants.
Particle boards are manufactured through a hot pressing process using wood materials (natural polymer materials) and adhesive, which find common usage in indoor decorative finishing materials. Flame-retardant particleboard, crucial for fire safety in such applications, undergoes performance analysis that includes assessing temperature distribution across its facing surface and temperature increase on the backside surface during facade combustion, yielding critical insights into fire scenario development. In this study, a compact flame spread apparatus is utilized to examine the flame retardancy and combustion behavior of particle boards, with a specific emphasis on the application of cost-effective flame retardants, encompassing aluminum hypophosphite (ALHP), an intumescent flame retardant (IFR) comprising ammonium polyphosphate (APP), melamine (MEL), and Dipentaerythritol (DPE), alongside magnesium hydroxide (MDH), and their associated combustion characteristics. The D values, representing the vertical distance from the ignition point (IP) to P (the temperature point at 300 °C farthest from IP), are measured using a compact temperature distribution measurement platform. For MDH/PB, APP + MEL + DPE/PB, and ALHP/PB samples, the respective D values of 145.79 mm, 117.81 mm, and 118.57 mm indicate reductions of 11.11%, 28.17%, and 27.71%, compared to the untreated sample's value of 164.02 mm. The particle boards treated with ALHP, IFR, and MDH demonstrated distinct flame-retardant mechanisms. MDH/PB relied on the thermal decomposition of MDH to produce MgO and HO for flame retardancy, while APP + MEL + DPE/PB achieved flame retardancy through a cross-linked structure with char expansion, polyphosphate, and pyrophosphate during combustion. On the other hand, ALHP/PB attained flame retardancy by reacting with wood materials and adhesives, forming a stable condensed P-N-C structure. This study serves as a performance reference for the production of cost-effective flame-resistant particleboards and offers a practical method for assessing its fire-resistant properties when used as a decorative finishing material on facades in real fire situations.
PubMed: 38231928
DOI: 10.3390/polym15234479 -
Journal of Ethnopharmacology Oct 2023Cough-variant asthma (CVA) is one of the most common causes of chronic cough. Its pathogenesis is closely related to chronic airway inflammation and airway...
ETHNOPHARMACOLOGICAL RELEVANCE
Cough-variant asthma (CVA) is one of the most common causes of chronic cough. Its pathogenesis is closely related to chronic airway inflammation and airway hyperresponsiveness. CVA belongs to the category of "wind cough" in Traditional Chinese medicine (TCM). Zi-Su-Zi decoction (ZSD) is a Chinese herbal formula that is clinically used for the treatment of cough and asthma, especially CVA. However, the mechanism of action remains unclear.
AIM OF THE STUDY
In this study, we aimed to explore the potential mechanism by which ZSD improves CVA airway hyperresponsiveness.
MATERIALS AND METHODS
The targets of ZSD in CVA were studied using a Network pharmacology. The main chemical components of ZSD were detected and analyzed using ultra-high-pressure liquid chromatography (UHPLC-MS/MS). In animal experiments, the rat model of CVA was established using Ovalbumin (OVA)/Aluminum hydroxide (AL(OH)3) sensitization. Moreover, the experiment also evaluated cough symptoms, percentage of eosinophils (EOS%), pulmonary function tests, histopathological sections, blood cytokine levels, mRNA and protein levels.
RESULTS
The results showed that Network pharmacology suggested 276 targets of ZSD and CVA and found that ZSD treatment with CVA was closely related to the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. UHPLC-MS/MS revealed that ZSD contained 52 main chemical components. Compared with the model group, the cough symptoms of the rats in the different ZSD concentration groups were relieved, the EOS% index was lowered, and body weight was increased. HE staining showed that ZSD reduced airway inflammation, edema and hyperplasia, thereby improving the pathological structure of lung tissue, and the effect of high-dose ZSD was especially significant. Our most important finding was that ZSD blocked the entry of hypoxia-inducible factor-1α (HIF-1α), signal transducer and activator of transcription-3 (STAT3) and nuclear factor kappa-B (NF-κB) into the nucleus by interfering with PI3K/AKT1/mechanistic target of rapamycin (mTOR), and janus kinase 2 (JAK2) signaling factors. Consequently, inhibiting the release of cytokines and immunoglobulin-E, thereby reducing airway hyperresponsiveness (AHR) and partially reverses airway remodeling.
CONCLUSIONS
This study showed that ZSD can improve airway hyperresponsiveness and partially reverse airway remodeling by inhibiting the PI3K/AKT1/mTOR, JAK2/STAT3 and HIF-1α/NF-κB signaling pathways. Therefore, ZSD is an effective prescription for the treatment of CVA.
Topics: Rats; Animals; NF-kappa B; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Phosphatidylinositol 3-Kinase; Cough; Janus Kinase 2; Airway Remodeling; Tandem Mass Spectrometry; Asthma; Signal Transduction; TOR Serine-Threonine Kinases; Cytokines; Inflammation
PubMed: 37187363
DOI: 10.1016/j.jep.2023.116637 -
Journal of Pharmaceutical Sciences Feb 2024Aluminum hydroxide adjuvants are widely used in human vaccines, such as diphtheria, tetanus, hepatitis A and hepatitis B vaccines. The adsorption of antigens on aluminum...
Aluminum hydroxide adjuvants are widely used in human vaccines, such as diphtheria, tetanus, hepatitis A and hepatitis B vaccines. The adsorption of antigens on aluminum hydroxide adjuvants determines the immune boosting effect of vaccines, but it is not clear how changes in physicochemical properties resulting from the production and formulation processes affect the adsorption of aluminum hydroxide adjuvants with antigens. In this study, the commercial aluminum hydroxide adjuvant Alhydrogel® was pretreated by commonly used processes such as autoclaving and calcination, and the changes of aluminum hydroxide adjuvant in physicochemical properties during the treatment were then comprehensively characterized. The adsorption of ovalbumin (OVA) with treated Alhydrogel®, was also investigated, it was found that the decrease in specific surface area caused by the autoclaving process reduced the adsorptive capacity of the antigen, and the adsorptive strength of antigen was decreased only when the surface hydroxyl groups and chemically bound water of adjuvant were reduced by calcination. These findings help to optimize the production and formulation process of adjuvants for the rational regulation of antigen adsorption in vaccines.
Topics: Humans; Aluminum Hydroxide; Aluminum; Adsorption; Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Hepatitis B Vaccines
PubMed: 37813301
DOI: 10.1016/j.xphs.2023.10.009 -
Materials (Basel, Switzerland) Oct 2023We investigated three calcium silicate-based sealers with respect to their chemical characterization, cytotoxicity, and attachment to RAW264.7 cells. BioRoot RCS (BR),...
We investigated three calcium silicate-based sealers with respect to their chemical characterization, cytotoxicity, and attachment to RAW264.7 cells. BioRoot RCS (BR), Bio-C Sealer (BC), and Sealer Plus BC (SPBC) were assessed using Fourier transform infrared spectroscopy (FTIR), X-ray fluorescence spectroscopy (XRF), and energy-dispersive X-ray spectroscopy (EDX) (n = 4) for elemental characterization, and using scanning electron microscopy (SEM) to evaluate cell morphology and adhesion. Cytotoxicity was determined at different dilutions (1:1, 1:2, and 1:5) using the succinate dehydrogenase activity (MTT assay). Statistical analysis was performed for normal distribution using the Shapiro-Wilk test and for homoscedasticity using Levene's test, and one-way ANOVA, Tukey's/Dunnett's post hoc tests for cell viability and XRF (α = 0.05). Calcium silicate hydrate and calcium hydroxide were detected by FTIR in all groups. EDX detected a higher calcium content for BR and SPBC and aluminum only in the premixed sealers. XRF detected the highest calcium release in BR ( < 0.05). The surface morphology showed irregular precipitates for all the sealers. SPBC at a 1:2 dilution resulted in the lowest cell viability compared to BR ( < 0.05) and BC ( < 0.05). The calcium silicate-based sealers produced a statistically significant reduction in cellular viability at a 1:1 dilution compared to the control group ( < 0.0001). All the sealers maintained viability above 70%.
PubMed: 37895687
DOI: 10.3390/ma16206705 -
ACS Omega Jan 2024Compounded aluminum hydroxide (ATH) flame retardants have been widely used for their low cost and environmentally friendly characteristics. However, previous research...
Compounded aluminum hydroxide (ATH) flame retardants have been widely used for their low cost and environmentally friendly characteristics. However, previous research lacks a systematic and comprehensive comparison. In addition, the combustion characteristics and phase characterization of asphalt binders are not taken into account either. In this work, flame retardants, for instance, APP, SbO, ZB, and LDHs, were compounded with ATH. The flame retardant behavior, together with the smoke suppression behavior, of asphalt binders with compounded flame retardants was determined by LOI and CCT. Furthermore, mechanisms on flame retardants were investigated. It was found that ATH compounded with ZB significantly reduced the heat smoke release and suppressed the formation of toxic volatiles during asphalt combustion. This was because ATH/ZB facilitated the formation of polyaromatic structures and improved the resistance of the char layer. ATH compounded with APP showed an antagonistic effect in the limiting oxygen test because the reaction between ATH and APP inhibited and delayed the decomposition of ATH during asphalt combustion with more aluminum phosphate presenting relatively poor barrier properties produced.
PubMed: 38250418
DOI: 10.1021/acsomega.3c08094