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Journal of Separation Science Oct 2023Imidazoquinoline gallamide is a toll-like receptor 7/8 agonist, belongs to the imidazoquinoline class, has the potential to activate antigen-presenting cells, and...
Development of liquid chromatography-triple quadrupole mass spectrometric method for the quantitative determination of a novel adjuvant, Imidazoquinoline gallamide in aluminum hydroxide gel-Imidazoquinoline gallamide and COVAXIN.
Imidazoquinoline gallamide is a toll-like receptor 7/8 agonist, belongs to the imidazoquinoline class, has the potential to activate antigen-presenting cells, and enhances immune response, primarily Th1 response. The COVAXIN is a whole virion inactivated Coronavirus disease 2019 vaccine formulated with this novel adjuvant called, aluminum hydroxide gel Imidazoquinoline gallamide, wherein, Imidazoquinoline gallamide is chemisorbed onto aluminum hydroxide gel. Herein, an analytical method based on liquid chromatography-tandem mass spectrometry was developed to identify and quantify Imidazoquinoline gallamide in aluminum hydroxide gel Imidazoquinoline gallamide and COVAXIN. The multiple reaction monitoring transitions were optimized for Imidazoquinoline gallamide quantification are [M+H] ions with 512.24→343.19 m/z (quantifier ion) and 512.24→360.22 m/z (qualifier ion). The developed method was validated as per the international conference on harmonization quality2 revison1 guidelines. The method was linear in the range of 0.025-10 µg/mL with a coefficient of determination of 0.9985 and the limit of quantification is 0.025 µg/mL. The accuracy was in the range of 82-121 % and intra- and inter-day precision was less than 7.1% and 5.39%, respectively. The expanded uncertainty results are 9.2% for Imidazoquinoline gallamide in the sample. The validated method was successfully applied to evaluate Imidazoquinoline gallamide concentration in every batch of COVAXIN.
Topics: Humans; COVID-19 Vaccines; Aluminum Hydroxide; Tandem Mass Spectrometry; Chromatography, Liquid; Adjuvants, Pharmaceutic; Reproducibility of Results; Ions; Chromatography, High Pressure Liquid
PubMed: 37609812
DOI: 10.1002/jssc.202300380 -
Archives of Razi Institute Dec 2023Foot-and-mouth disease (FMD) has a high prevalence in cloven-hoofed animals. It is also highly contagious and remains a serious threat to livestock worldwide. Despite... (Comparative Study)
Comparative Study
Foot-and-mouth disease (FMD) has a high prevalence in cloven-hoofed animals. It is also highly contagious and remains a serious threat to livestock worldwide. Despite the widespread vaccination program in Iran, outbreaks of FMD continue to occur. Vaccination is one of the most effective methods of preventing FMD. The vaccines used in Iran are of the inactivated type and contain several serotypes. Since inactivated vaccines without adjuvants do not induce a high and durable antibody response, it is necessary to use adjuvants. Montanide ISA 206 VG is a mineral oil-based adjuvant that produces a water-in-oil-in-water (w:o:w) emulsion in vaccine preparations. However, a large number of manufacturers in Iran and around the world still use alum adjuvant (with or without saponin) to produce the FMD vaccine. This study used Montanide ISA 206 and alum adjuvants to administer the O2010 serotype of the FMD virus to goats. A total of six goats were divided randomly into three groups. Vaccines were administered subcutaneously twice, at a one-month interval. Blood sampling was done at different times, and the micro-neutralization method was used to measure the neutralizing antibody titer in each serum. Seven days after the second vaccination, the alum group's antibody titer was higher but not statistically significant. However, from the 28th day after the second injection until the end of the study, the Montanide ISA 206 group's antibody titer was significantly higher than that of the alum group. Six months after the second injection, the antibody titer in the ISA 206 group remained at the peak level, while in the alum group, it decreased and reached the minimum protective level. Nine months after the second injection, the antibody titer remained at its peak level in the ISA 206 group, whereas it dropped significantly in the alum group. Based on the findings, ISA 206 VG is capable of generating long-term humoral immunity in goats against the FMD serotype O2010 and could replace aluminum hydroxide adjuvants in FMD vaccine preparations.
Topics: Animals; Goats; Aluminum Hydroxide; Foot-and-Mouth Disease Virus; Goat Diseases; Foot-and-Mouth Disease; Adjuvants, Immunologic; Viral Vaccines; Antibodies, Neutralizing; Antibodies, Viral; Iran; Oleic Acids; Mannitol
PubMed: 38828163
DOI: 10.32592/ARI.2023.78.6.1843 -
Journal of Ethnopharmacology Jan 2024Angelica decursiva Franchet & Savatier is a traditional medicinal plant used to treat asthma, cough, headache, pyrexia and thick phlegm in China, Japan and Korea. A....
ETHNOPHARMACOLOGICAL RELEVANCE
Angelica decursiva Franchet & Savatier is a traditional medicinal plant used to treat asthma, cough, headache, pyrexia and thick phlegm in China, Japan and Korea. A. decursiva contains many types of coumarins, which can exert several pharmacological activities including anti-inflammatory and antioxidant properties for treating various diseases such as pneumonitis, atopic dermatitis, diabetes, and Alzheimer's disease.
AIM OF THE STUDY
In this study, we analyzed the components of A. decursiva ethanol extract (ADE) by high performance liquid chromatography (HPLC) and investigated the therapeutic effects of ADE against allergic asthma using lipopolysaccharide (LPS) stimulated RAW264.7 cells and an ovalbumin (OVA)-exposed allergic asthma model. To elucidate the mechanism of action of ADE, we examined the protein expression through network pharmacological analysis.
MATERIALS AND METHODS
To establish asthma model, the mice were sensitized on day 0 and 14 via intraperitoneal injection of OVA with aluminum hydroxide. The mice were inhaled with OVA using an ultrasonic nebulizer on day 21, 22 and 23. ADE (50 and 100 mg/kg) was administered to mice by oral gave form day 18-23. On day 24, airway hyperresponsiveness (AHR) was measured using flexivent. On day 25, the mice were sacrificed and collected bronchoalveolar lavage fluids (BALF), serum and lung tissue. In LPS-stimulated RAW264.7 cell, nitric oxide and cytokines were measured. Additionally, expression of nuclear factor erythroid-2-related factor (Nrf2) and suppression of nuclear factor (NF)-κB were detected using double-immunofluorescence.
RESULTS
We detected the five coumarin components which included nodakenin, umbelliferon, (-)-marmesin (=nodakenetin), bergapten, and decursin, in ADE by high performance liquid chromatography. Treatment with ADE decreased the production of nitric oxide, interleukin (IL)-6 and tumor necrosis factor (TNF)-α in LPS-stimulated RAW264.7 cells accompanied by the enhanced expression of nuclear factor erythroid-2-related factor (Nrf2) and suppression of nuclear factor (NF)-κB. In the asthma model, the administration of ADE reduced inflammatory cell count and airway hyperresponsiveness in OVA-exposed animals with decreased levels of IL-4, IL-13, and OVA-specific immunoglobulin E. These results were accompanied by the reduction of pulmonary inflammation and mucus secretion. Furthermore, ADE administration inhibited the expression of NF-κB and matrix metalloproteinase (MMP)-9 in OVA-exposed animals, which was consistent with the results of network pharmacological analysis.
CONCLUSION
This study demonstrated that ADE effectively attenuated allergic inflammation induced by OVA inhalation through the enhancement of Nrf2 expression and suppression of NF-κB expression. Therefore, ADE may be a potential therapeutic agent for controlling asthma.
Topics: Animals; Mice; Ovalbumin; NF-kappa B; NF-E2-Related Factor 2; Lipopolysaccharides; Matrix Metalloproteinase 9; Angelica; Nitric Oxide; Asthma; Hypersensitivity; Lung; Pneumonia; Bronchoalveolar Lavage Fluid; Interleukin-6; Mice, Inbred BALB C; Disease Models, Animal
PubMed: 37423516
DOI: 10.1016/j.jep.2023.116863 -
Bioconjugate Chemistry Oct 2023Currently approved pharmacotherapies for opioid use disorders (OUDs) and overdose reversal agents are insufficient to slow the spread of OUDs due to the proliferation of...
Currently approved pharmacotherapies for opioid use disorders (OUDs) and overdose reversal agents are insufficient to slow the spread of OUDs due to the proliferation of fentanyl. This is evident in the 31% rise in drug overdose deaths from 2019 to 2022, with rates increasing from 21.6 to 28.3 overdoses per 100,000 deaths. Vaccines are a potential alternative or adjunct therapy for the treatment of several substance use disorders (nicotine, cocaine) but have shown limited clinical success due to suboptimal antibody titers. In this study, we demonstrate that coconjugation of a Toll-like receptor 7/8 (TLR7/8) agonist (UM-3006) alongside a fentanyl-based hapten (F) on the surface of the carrier protein cross-reactive material 197 (CRM) significantly increased generation of high-affinity fentanyl-specific antibodies. This demonstrated enhanced protection against fentanyl challenges relative to an unconjugated (admix) adjuvant control in mice. Inclusion of aluminum hydroxide (alum) adjuvant further increased titers and enhanced protection, as determined by analysis of fentanyl concentration in serum and brain tissue. Collectively, our findings present a promising approach to enhance the efficacy of antiopioid vaccines, underscoring the need for extensive exploration of TLR7/8 agonist conjugates as a compelling strategy to combat opioid use disorders.
Topics: Animals; Mice; Toll-Like Receptor 7; Fentanyl; Adjuvants, Immunologic; Antigens; Vaccines; Haptens; Opioid-Related Disorders; Analgesics, Opioid
PubMed: 37758302
DOI: 10.1021/acs.bioconjchem.3c00347 -
Environmental Research Oct 2023Textile and pharmaceutical effluents contain significant amounts of dyes and antibiotics, which pose a serious threat to the ecosystem when discharged directly....
Simultaneous adsorption of methylene blue and amoxicillin by starch-impregnated MgAl layered double hydroxide: Parametric optimization, isothermal studies and thermo-kinetic analysis.
Textile and pharmaceutical effluents contain significant amounts of dyes and antibiotics, which pose a serious threat to the ecosystem when discharged directly. Therefore, they should be treated by facile treatment techniques using low-cost materials. Layered double hydroxide (LDH) and its hybrids have emerged as robust and economic adsorbents for water treatment. Herein, magnesium/aluminum LDH and its starch-based composite were synthesized by a co-precipitation technique. The physicochemical features of the developed adsorbents were thoroughly characterized using various analytical tools. The developed materials were tested for the eradication of methylene blue (MB) and amoxicillin (AMX) in batch mode adsorption by varying operating conditions. Adsorption performance depends on the solution's pH. Under optimum adsorption conditions of pH 11, adsorbent dosage of 50 mg/L, and treatment time of 120 min, starch-impregnated MgAl-LDH exhibited maximum MB and AMX adsorption capacities of 114.94 and 48.08 mg/g, respectively. The adsorption mechanism states that hydrogen bonds and weak van der Waals forces are responsible for the removal of pollutants by the developed materials. Moreover, equilibrium and kinetic studies revealed that the removal of dye and antibiotic followed the Freundlich and Langmuir models with the pseudo-second-order reaction kinetics, respectively. The spent adsorbents were regenerated using 0.1 M HCl (for MB) and methanol (for AMX) eluent, and reusability studies ensured that the developed adsorbents retained their performance for up to four consecutive adsorption/desorption cycles. MgAl-LDH and its starch-based hybrid could thus be used to effectively remove organic contaminants from wastewater streams on a commercial scale.
Topics: Kinetics; Methylene Blue; Adsorption; Amoxicillin; Ecosystem; Water Pollutants, Chemical; Hydroxides; Coloring Agents; Anti-Bacterial Agents; Hydrogen-Ion Concentration
PubMed: 37437872
DOI: 10.1016/j.envres.2023.116610 -
The Journal of Physical Chemistry. C,... Jul 2023Improving the performance of organic optoelectronics has been under vigorous research for decades. Recently, polaritonics has been introduced as a technology that has...
Improving the performance of organic optoelectronics has been under vigorous research for decades. Recently, polaritonics has been introduced as a technology that has the potential to improve the optical, electrical, and chemical properties of materials and devices. However, polaritons have been mainly studied in optical microcavities that are made by vacuum deposition processes, which are costly, unavailable to many, and incompatible with printed optoelectronics methods. Efforts toward the fabrication of polariton microcavities with solution-processed techniques have been utterly absent. Herein, we demonstrate for the first time strong light-matter coupling and polariton photoluminescence in an organic microcavity consisting of an aluminum mirror and a distributed Bragg reflector (DBR) made by sequential dip coating of titanium hydroxide/poly(vinyl alcohol) (TiOH/PVA) and Nafion films. To fabricate and develop the solution-processed DBRs and microcavities, we automatized a dip-coating device that allowed us to produce sub-100 nm films consistently over many dip-coating cycles. Owning to the solution-based nature of our DBRs, our results pave the way to the realization of polariton optoelectronic devices beyond physical deposition methods.
PubMed: 37529668
DOI: 10.1021/acs.jpcc.3c01457 -
Journal of Chromatography. A Aug 2023A magnetic solid-phase extraction (MSPE) method was developed for the enrichment of trace amounts of estrone (E1), 17-β-estradiol (E2) and bisphenol A (BPA) from...
A magnetic solid-phase extraction (MSPE) method was developed for the enrichment of trace amounts of estrone (E1), 17-β-estradiol (E2) and bisphenol A (BPA) from aqueous samples using the Rubber-FeO@SiO@Mg-Al Layered double hydroxide followed by determination by HPLC. The proposed sorbent was characterized by X-ray diffraction, Field emission scanning electron microscopy, Fourier transform infrared spectroscopy, Vibrating-sample magnetometer, Thermal gravimetric analysis, N adsorption/desorption Brunauer-Emmett-Teller surface analysis, Barrett-Joyner-Halenda pore size analysis and Energy dispersive X-ray spectroscopy. Factors affecting the extraction efficiency such as pH, ionic strength, extraction temperature and time, desorption solvent and time were optimized. The limit of detection and quantification were obtained as 0.33, 1 µg L for the E1 and E2 and BPA, respectively. Also, linear range of the method were 1-150, 1-100 and 1-150 µg Lfor E1, E2, and BPA, respectively. Relative standard deviations (RSD%) for the repeatability of extraction on one sorbent were obtained as 2.98, 1.31 and 3.50%, also, sorbent to sorbent repeatability were investigated and RSD% values were obtained as 7.58, 8.35 and 8.12% for E1, E2 and BPA, respectively.
Topics: Aluminum; Magnesium; Rubber; Estrone; Silicon Dioxide; Solid Phase Extraction; Hydroxides; Adsorption; Magnetic Phenomena; Limit of Detection
PubMed: 37354774
DOI: 10.1016/j.chroma.2023.464129 -
Immunology Letters Aug 2023Shrimp is among the most sensitizing food allergens and has been associated with many anaphylaxis reactions. However, there is still a shortage of studies that enable a...
Shrimp is among the most sensitizing food allergens and has been associated with many anaphylaxis reactions. However, there is still a shortage of studies that enable a systematic understanding of this disease and the investigation of new therapeutic approaches. This study aimed to develop a new experimental model of shrimp allergy that could enable the evaluation of new prophylactic treatments. BALB/c mice were subcutaneously sensitized with 100 μg of shrimp proteins of Litopenaeus vannamei adsorbed in 1 mg of aluminum hydroxide on day 0, and a booster (100 µg of shrimp proteins only) on day 14. The oral challenge protocol was based on the addition of 5 mg/ml of shrimp proteins to water from day 21 to day 35. Analysis of shrimp extract content detected at least 4 of the major allergens reported to L. vannamei. In response to the sensitization, allergic mice showed significantly enhanced IL-4 and IL-10 production in restimulated cervical draining lymph node cells. High detection of serum anti-shrimp IgE and IgG1 suggested the development of allergies to shrimp while Passive Cutaneous Anaphylaxis assay revealed an IgE-mediated response. Immunoblotting analysis revealed that Allergic mice developed antibodies to multiple antigens present in the shrimp extract. These observations were supported by the detection of anti-shrimp IgA production in intestinal lavage samples and morphometric intestinal mucosal changes. Therefore, this experimental protocol can be a tool to evaluate prophylactic and therapeutic approaches.
Topics: Animals; Mice; Immunoglobulin E; Food Hypersensitivity; Anaphylaxis; Allergens; Plant Extracts
PubMed: 37315848
DOI: 10.1016/j.imlet.2023.06.007 -
Vaccine Jul 2023Countermeasures against Zika virus (ZIKV) epidemics are urgently needed. In this study we generated a ZIKV virus-like particle (VLP) based vaccine candidate and assessed...
Countermeasures against Zika virus (ZIKV) epidemics are urgently needed. In this study we generated a ZIKV virus-like particle (VLP) based vaccine candidate and assessed the immunogenicity of these particles in mice. The ZIKV-VLPs were morphologically similar to ZIKV by electron microscopy and were recognized by anti-Flavivirus neutralising antibodies. We observed that a single dose of unadjuvanted ZIKV-VLPs, or inactivated ZIKV, generated an immune response that lasted over 6 months, but did not neutralize ZIKV infection of cells in vitro. However, when we co-administered the ZIKV VLPs with either Aluminium hydroxide (Alhydrogel®; Alum), AddaVax or PamCys we observed that Alum was the most effective in a single dose regime, since it not only produced antibodies that neutralized the virus, but also generated a greater number of antigen-specific memory B cells. We additionally observed that the generation of the neutralising antibodies persisted for up to 6 months. Our results suggest that a single dose ZIKV VLPs could be a suitable single dose vaccine candidate for use in outbreak settings.
Topics: Animals; Mice; Zika Virus; Antibodies, Neutralizing; Zika Virus Infection; Antibodies, Viral; Viral Vaccines; Adenoviridae
PubMed: 37391311
DOI: 10.1016/j.vaccine.2023.06.068 -
Vaccine Oct 2023The development of safe and effective second-generation COVID-19 vaccines to improve affordability and storage stability requirements remains a high priority to expand... (Comparative Study)
Comparative Study
Formulation development and comparability studies with an aluminum-salt adjuvanted SARS-CoV-2 spike ferritin nanoparticle vaccine antigen produced from two different cell lines.
The development of safe and effective second-generation COVID-19 vaccines to improve affordability and storage stability requirements remains a high priority to expand global coverage. In this report, we describe formulation development and comparability studies with a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen (called DCFHP), when produced in two different cell lines and formulated with an aluminum-salt adjuvant (Alhydrogel, AH). Varying levels of phosphate buffer altered the extent and strength of antigen-adjuvant interactions, and these formulations were evaluated for their (1) in vivo performance in mice and (2) in vitro stability profiles. Unadjuvanted DCFHP produced minimal immune responses while AH-adjuvanted formulations elicited greatly enhanced pseudovirus neutralization titers independent of ∼100%, ∼40% or ∼10% of the DCFHP antigen adsorbed to AH. These formulations differed, however, in their in vitro stability properties as determined by biophysical studies and a competitive ELISA for measuring ACE2 receptor binding of AH-bound antigen. Interestingly, after one month of 4°C storage, small increases in antigenicity with concomitant decreases in the ability to desorb the antigen from the AH were observed. Finally, we performed a comparability assessment of DCFHP antigen produced in Expi293 and CHO cells, which displayed expected differences in their N-linked oligosaccharide profiles. Despite consisting of different DCFHP glycoforms, these two preparations were highly similar in their key quality attributes including molecular size, structural integrity, conformational stability, binding to ACE2 receptor and mouse immunogenicity profiles. Taken together, these studies support future preclinical and clinical development of an AH-adjuvanted DCFHP vaccine candidate produced in CHO cells.
Topics: Animals; Spike Glycoprotein, Coronavirus; COVID-19 Vaccines; Adjuvants, Immunologic; Mice; Ferritins; SARS-CoV-2; COVID-19; Nanoparticles; Humans; Antibodies, Neutralizing; Female; Antibodies, Viral; Cell Line; Cricetulus; CHO Cells; Mice, Inbred BALB C; Aluminum Hydroxide; Immunogenicity, Vaccine; Nanovaccines
PubMed: 37620203
DOI: 10.1016/j.vaccine.2023.08.037