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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 -
Journal of Pharmaceutical Sciences Jan 2020Subunit vaccines often contain colloidal aluminum salt-based adjuvants to activate the innate immune system. These aluminum salts consist of micrometer-sized aggregates.... (Comparative Study)
Comparative Study
Subunit vaccines often contain colloidal aluminum salt-based adjuvants to activate the innate immune system. These aluminum salts consist of micrometer-sized aggregates. It is well-known that particle size affects the adjuvant effect of particulate adjuvants. In this study, the activation of human monocytes by hexagonal-shaped gibbsite (ø = 210 ± 40 nm) and rod-shaped boehmite (ø = 83 ± 827 nm) was compared with classical aluminum oxyhydroxide adjuvant (alum). To this end, human primary monocytes were cultured in the presence of alum, gibbsite, or boehmite. The transcriptome and proteome of the monocytes were investigated by using quantitative polymerase chain reaction and mass spectrometry. Human monocytic THP-1 cells were used to investigate the effect of the particles on cellular maturation, differentiation, activation, and cytokine secretion, as measured by flow cytometry and enzyme-linked immunosorbent assay. Each particle type resulted in a specific gene expression profile. IL-1ß and IL-6 secretion was significantly upregulated by boehmite and alum. Of the 7 surface markers investigated, only CD80 was significantly upregulated by alum and none by gibbsite or boehmite. Gibbsite hardly activated the monocytes. Boehmite activated human primary monocytes equally to alum, but induced a much milder stress-related response. Therefore, boehmite was identified as a promising adjuvant candidate.
Topics: Adjuvants, Immunologic; Aluminum Hydroxide; Aluminum Oxide; B7-1 Antigen; Cell Differentiation; Colloids; Drug Compounding; Humans; Immunity, Innate; Interleukin-1beta; Interleukin-6; Monocytes; Particle Size; THP-1 Cells; Transcriptome
PubMed: 31449816
DOI: 10.1016/j.xphs.2019.08.014 -
BMC Veterinary Research Jan 2014Toll-like receptor (TLR) agonists reportedly have potent antiviral and antitumor activities and may be a new kind of adjuvant for enhancing immune efficacy. Resiquimod...
BACKGROUND
Toll-like receptor (TLR) agonists reportedly have potent antiviral and antitumor activities and may be a new kind of adjuvant for enhancing immune efficacy. Resiquimod (R848) is an imidazoquinoline compound with potent antiviral activity and functions through the TLR7/TLR8 MyD88-dependent signaling pathway. Polyinosinic-polycytidylic acid [poly(I:C)] is a synthetic analog of double-stranded RNA that induces the production of pro-inflammatory cytokines by the activation of NF-κB through TLR3. This study investigated the potential of R848 and poly(I:C) as an adjuvant 146S foot-and-mouth disease virus (FMDV) vaccine formulated with aluminum hydroxide (Al(OH)₃).
RESULTS
Antibody titers to FMDV and CD8+ T cells were markedly enhanced in mice immunized to 146S FMDV + Al(OH)₃ + R848 + poly(I:C) compared with mice immunized to FMDV + ISA206. IFN-γ secretion substantially increased compared with IL-4 secretion by splenic T cells stimulated with FMDV antigens in vitro, suggesting that R848, poly(I:C), and with Al(OH)₃ together biased the immune response toward a Th1-type direction.
CONCLUSIONS
These results indicated that the R848 and poly(I:C) together with Al(OH)₃ enhanced humoral and cellular immune responses to immunization with 146S FMDV antigens. Thus, this new vaccine formulation can be used for FMDV prevention.
Topics: Adjuvants, Immunologic; Aluminum Hydroxide; Animals; Antibodies, Viral; Antibody Specificity; Female; Foot-and-Mouth Disease; Imidazoles; Mice; Mice, Inbred BALB C; Poly I-C; Spleen; T-Lymphocyte Subsets; Viral Vaccines
PubMed: 24386990
DOI: 10.1186/1746-6148-10-2 -
The Cochrane Database of Systematic... Nov 2014Background Tranexamic acid reduces haemorrhage through its antifibrinolytic effects. In a previous version of the present review, we found that tranexamic acid may... (Meta-Analysis)
Meta-Analysis Review
Background Tranexamic acid reduces haemorrhage through its antifibrinolytic effects. In a previous version of the present review, we found that tranexamic acid may reduce mortality. This review includes updated searches and new trials.Objectives To assess the effects of tranexamic acid versus no intervention, placebo or other antiulcer drugs for upper gastrointestinal bleeding.Search methods We updated the review by performing electronic database searches (Cochrane Central Register of Controlled Trials (CENTRAL),MEDLINE, EMBASE, Science Citation Index) and manual searches in July 2014.Selection criteriaRandomised controlled trials, irrespective of language or publication status.Data collection and analysis We used the standard methodological procedures of the The Cochrane Collaboration. All-cause mortality, bleeding and adverse events were the primary outcome measures. We performed fixed-effect and random-effects model meta-analyses and presented results as risk ratios (RRs) with 95% confidence intervals (CIs) and used I² as a measure of between-trial heterogeneity. We analysed tranexamic acid versus placebo or no intervention and tranexamic acid versus antiulcer drugs separately. To analyse sources of heterogeneity and robustness of the overall results, we performed subgroup, sensitivity and sequential analyses.Main results We included eight randomised controlled trials on tranexamic acid for upper gastrointestinal bleeding. Additionally, we identified one large ongoing pragmatic randomised controlled trial from which data are not yet available. Control groups were randomly assigned to placebo (seven trials) or no intervention (one trial). Two trials also included a control group randomly assigned to antiulcer drugs(lansoprazole or cimetidine). The included studies were published from 1973 to 2011. The number of participants randomly assigned ranged from 47 to 216 (median 204). All trials reported mortality. In total, 42 of 851 participants randomly assigned to tranexamic acid and 71 of 850 in the control group died (RR 0.60, 95% CI 0.42 to 0.87; P value 0.007; I² = 0%). The analysis was not confirmed when all participants in the intervention group with missing outcome data were included as treatment failures, or when the analysis was limited to trials with low risk of attrition bias. Rebleeding was diagnosed for 117 of 826 participants in the tranexamic acid group and for 146 of 825 participants in the control group (RR 0.80, 95% CI 0.64 to 1.00; P value 0.07; I² = 49%).We were able to evaluate the risk of serious adverse events on the basis of only four trials. Our analyses showed 'no evidence of a difference between tranexamic acid and control interventions regarding the risk of thromboembolic events.’ Tranexamic acid appeared to reduce the risk of surgery ina fixed-effect meta-analysis (RR 0.73, 95% CI 0.56 to 0.95), but this result was no longer statistically significant in a random-effects meta-analysis (RR 0.61, 95% CI 0.35 to 1.04; P value 0.07). No difference was apparent between tranexamic acid and placebo in the assessment of transfusion (RR 1.02, 95% CI 0.94 to 1.11; I² = 0%), and meta-analyses that compared tranexamic acid versus antiulcer drugs did not identify beneficial or detrimental effects of tranexamic acid for any of the outcomes assessed.Authors' conclusions This review found that tranexamic acid appears to have a beneficial effect on mortality, but a high dropout rate in some trials means that we cannot be sure of this until the findings of additional research are published. At the time of this update in 2014, one large study(8000 participants) is in progress, so this review will be much more informative in a few years. Further examination of tranexamic acid would require inclusion of high-quality randomised controlled trials. Timing of randomisation is essential to avoid attrition bias and to limit the number of withdrawals. Future trials may use a pragmatic design and should include all participants with suspected bleeding or with endoscopically verified bleeding, as well as a tranexamic placebo arm and co-administration of pump inhibitors and endoscopic therapy. Assessment of outcome measures in such studies should be clearly defined. Endoscopic examination with appropriate control of severe bleeding should be performed, as should endoscopic verification of clinically significant rebleeding. In addition, clinical measures of rebleeding should be included. Other important outcome measures include mortality (30-day or in-hospital), need for emergency surgery or blood transfusion and adverse events (major or minor).
Topics: Administration, Oral; Aluminum Hydroxide; Anti-Ulcer Agents; Antifibrinolytic Agents; Cimetidine; Drug Combinations; Endoscopy, Gastrointestinal; Gastrointestinal Hemorrhage; Humans; Injections, Intravenous; Lansoprazole; Magnesium; Magnesium Hydroxide; Randomized Controlled Trials as Topic; Tranexamic Acid
PubMed: 25414987
DOI: 10.1002/14651858.CD006640.pub3 -
Journal of Immunological Methods Jul 2015The mechanism behind the adjuvant effect of aluminum salts is poorly understood notwithstanding that aluminum salts have been used for decades in clinical vaccines. In...
The mechanism behind the adjuvant effect of aluminum salts is poorly understood notwithstanding that aluminum salts have been used for decades in clinical vaccines. In an aqueous environment and at a nearly neutral pH, the aluminum salts form particulate aggregates, and one plausible explanation of the lack of information regarding the mechanisms could be the absence of an efficient method of tracking phagocytosed aluminum adjuvants and thereby the intracellular location of the adjuvant. In this paper, we want to report upon the use of lumogallion staining enabling the detection of phagocytosed aluminum adjuvants inside viable cells. Including micromolar concentrations of lumogallion in the culture medium resulted in a strong fluorescence signal from cells that had phagocytosed the aluminum adjuvant. The fluorescence appeared as spots in the cytoplasm and by confocal microscopy and co-staining with probes presenting fluorescence in the far-red region of the spectrum, aluminum adjuvants could to a certain extent be identified as localized in acidic vesicles, i.e., lysosomes. Staining and detection of intracellular aluminum adjuvants was achieved not only by diffusion of lumogallion into the cytoplasm, thereby highlighting the presence of the adjuvant, but also by pre-staining the aluminum adjuvant prior to incubation with cells. Pre-staining of aluminum adjuvants resulted in bright fluorescent particulate aggregates that remained fluorescent for weeks and with only a minor reduction of fluorescence upon extensive washing or incubation with cells. Both aluminum oxyhydroxide and aluminum hydroxyphosphate, two of the most commonly used aluminum adjuvants in clinical vaccines, could be pre-stained with lumogallion and were easily tracked intracellularly after incubation with phagocytosing cells. Staining of viable cells using lumogallion will be a useful method in investigations of the mechanisms behind aluminum adjuvants' differentiation of antigen-presenting cells into inflammatory cells. Information will be gained regarding the phagosomal pathways and the events inside the phagosomes, and thereby the ultimate fate of phagocytosed aluminum adjuvants could be resolved.
Topics: Adjuvants, Immunologic; Aluminum Hydroxide; Aluminum Oxide; Animals; Benzenesulfonates; Cell Line, Tumor; Flavonoids; Fluorescent Dyes; Humans; Mice; Mice, Inbred C57BL; Microscopy, Confocal; Phagocytosis; Phosphates; Staining and Labeling
PubMed: 25896212
DOI: 10.1016/j.jim.2015.04.008 -
Gut Jun 1979Antacids can reduce gastroduodenal acidity for long periods if taken in substantial quantities after food. Their healing effect on gastric ulcer is minimal, if present... (Clinical Trial)
Clinical Trial Comparative Study Review
Antacids can reduce gastroduodenal acidity for long periods if taken in substantial quantities after food. Their healing effect on gastric ulcer is minimal, if present at all, and easily overwhelmed by the benefit obtained from admission to hospital. Intensive antacid therapy appears effective in healing duodenal ulcer and preventing haemorrhage from stress ulcer, and is comparable in these respects with cimetidine but with a higher incidence of side-effects. Clinical impression strongly suggests that antacids relieve pain in peptic ulcer but objective confirmation is lacking.
Topics: Aluminum Hydroxide; Antacids; Calcium Carbonate; Cimetidine; Clinical Trials as Topic; Double-Blind Method; Gastric Juice; Humans; Hydrogen-Ion Concentration; Pain; Peptic Ulcer; Peptic Ulcer Hemorrhage; Time Factors
PubMed: 38192
DOI: 10.1136/gut.20.6.538 -
Journal of Immunology (Baltimore, Md. :... Jan 2017Vaccine adjuvant effects in the CD4-deficient condition largely remain unknown. We investigated the roles of combined monophosphoryl lipid A (MPL) and aluminum hydroxide...
Roles of Aluminum Hydroxide and Monophosphoryl Lipid A Adjuvants in Overcoming CD4+ T Cell Deficiency To Induce Isotype-Switched IgG Antibody Responses and Protection by T-Dependent Influenza Vaccine.
Vaccine adjuvant effects in the CD4-deficient condition largely remain unknown. We investigated the roles of combined monophosphoryl lipid A (MPL) and aluminum hydroxide (Alum) adjuvant (MPL+Alum) in inducing immunity after immunization of CD4 knockout (CD4KO) and wild-type (WT) mice with T-dependent influenza vaccine. MPL+Alum adjuvant mediated IgG isotype-switched Abs, IgG-secreting cell responses, and protection in CD4KO mice, which were comparable to those in WT mice. In contrast, Alum adjuvant effects were dependent on CD4 T cells. MPL+Alum adjuvant was effective in recruiting monocytes and neutrophils as well as in protecting macrophages from Alum-mediated cell loss at the injection site in CD4KO mice. MPL+Alum appeared to attenuate MPL-induced inflammatory responses in WT mice, likely improving the safety. Additional studies in CD4-depleted WT mice and MHC class II KO mice suggest that MHC class II APCs contribute to providing alternative B cell help in the CD4-deficient condition in the context of MPL+Alum-adjuvanted vaccination.
Topics: Adjuvants, Immunologic; Aluminum Hydroxide; Animals; Antibodies, Viral; Antigen-Presenting Cells; CD4-Positive T-Lymphocytes; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Immunoglobulin Class Switching; Immunoglobulin G; Influenza Vaccines; Lipid A; Lymphocyte Activation; Male; Mice; Mice, Inbred C57BL; Mice, Knockout
PubMed: 27881702
DOI: 10.4049/jimmunol.1600173 -
International Journal of Nanomedicine 2015Hydrotalcite-like compounds are two-dimensional inorganic nanolayers also known as clay minerals or anionic clays or layered double hydroxides/layered hydroxy salts, and... (Review)
Review
Hydrotalcite-like compounds are two-dimensional inorganic nanolayers also known as clay minerals or anionic clays or layered double hydroxides/layered hydroxy salts, and have emerged as a single type of material with numerous biomedical applications, such as drug delivery, gene delivery, cosmetics, and biosensing. Inorganic nanolayers are promising materials due to their fascinating properties, such as ease of preparation, ability to intercalate different type of anions (inorganic, organic, biomolecules, and even genes), high thermal stability, delivery of intercalated anions in a sustained manner, high biocompatibility, and easy biodegradation. Inorganic nanolayers have been the focus for researchers over the last decade, resulting in widening application horizons, especially in the field of biomedical science. These nanolayers have been widely applied in drug and gene delivery. They have also been applied in biosensing technology, and most recently in bioimaging science. The suitability of inorganic nanolayers for application in drug delivery, gene delivery, biosensing technology, and bioimaging science makes them ideal materials to be applied for theranostic purposes. In this paper, we review the structure, methods of preparation, and latest advances made by inorganic nanolayers in such biomedical applications as drug delivery, gene delivery, biosensing, and bioimaging.
Topics: Aluminum Hydroxide; Aluminum Silicates; Anti-Infective Agents; Antineoplastic Agents; Antitubercular Agents; Biocompatible Materials; Biosensing Techniques; Clay; Drug Delivery Systems; Gene Transfer Techniques; Hydroxides; Intercalating Agents; Magnesium Hydroxide; Nanostructures
PubMed: 26366081
DOI: 10.2147/IJN.S72330 -
International Journal of Molecular... May 2023In this paper, water hyacinth is used to prepare biochar (WBC). A biochar-aluminum-zinc-layered double hydroxide composite functional material (WL) is synthesized via a...
In this paper, water hyacinth is used to prepare biochar (WBC). A biochar-aluminum-zinc-layered double hydroxide composite functional material (WL) is synthesized via a simple co-precipitation method which is used to adsorb and remove benzotriazole (BTA) and lead (Pb) in an aqueous solution. In particular, this research paper uses various characterization methods to analyze WL and to explore the adsorption performance and adsorption mechanism of WL on BTA and Pb in an aqueous solution through batch adsorption experiments combined with model fitting and spectroscopy techniques. The results indicate that the surface of WL contains a thick sheet-like structure with many wrinkles which would provide many adsorption sites for pollutants. At room temperature (25 °C), the maximum adsorption capacities of WL on BTA and Pb are 248.44 mg·g and 227.13 mg·g, respectively. In a binary system, during the process of using WL to adsorb BTA and Pb, compared with that in the absorption on Pb, WL shows a stronger affinity in the adsorption on BTA, and BTA would thus be preferred in the absorption process. The adsorption process of WL on BTA and Pb is spontaneous and is endothermic monolayer chemisorption. In addition, the adsorption of WL on BTA and Pb involves many mechanisms, but the main adsorption mechanisms are different. Among them, hydrogen bonding dominates the adsorption on BTA, while functional groups (C-O and C=O) complexation dominates the adsorption on Pb. When WL adsorbs BTA and Pb, the coexistence of cations (K, Na, and Ca) has a strong anti-interference ability, and WL can use a lower concentration of fulvic acid (FA) (<20 mg·L) to improve its adsorption performance. Last but not least, WL has a stable regenerative performance in a one-component system and a binary system, which indicates that WL has excellent potential for the remediation of BTA and Pb in water.
Topics: Adsorption; Eichhornia; Lead; Charcoal; Aluminum Hydroxide; Water Pollutants, Chemical; Kinetics
PubMed: 37240279
DOI: 10.3390/ijms24108936 -
The Journal of Infectious Diseases Nov 2008Dose-sparing strategies are being explored for vaccines against pandemic influenza. We evaluated the dose-sparing potential of aluminum hydroxide (AlOH) adjuvant. (Randomized Controlled Trial)
Randomized Controlled Trial
Safety and immunogenicity of an inactivated influenza A/H5N1 vaccine given with or without aluminum hydroxide to healthy adults: results of a phase I-II randomized clinical trial.
BACKGROUND
Dose-sparing strategies are being explored for vaccines against pandemic influenza. We evaluated the dose-sparing potential of aluminum hydroxide (AlOH) adjuvant.
METHODS
A total of 600 healthy subjects (age, 18-49 years) were randomized to receive 2 vaccinations 1 month apart with subvirion inactivated influenza A/H5N1 vaccine containing 7.5, 15, or 45 microg of hemagglutinin (HA), with or without 600 microg of aluminum hydroxide (AlOH), or 3.75 microg of HA, with or without 300 microg of AlOH. Serum specimens were obtained for antibody assays before and 1 month after each vaccination.
RESULTS
All formulations were safe. Injection site discomfort was more frequent in groups given vaccines with AlOH. Dose-related increases in antibody responses were noted after both vaccinations (P< .001) geometric mean titers of hemagglutination inhibition antibody in vaccines with and without AlOH, respectively, were 5.4 and 5.4 for subjects who received 3.75 microg of HA, 7.7 and 5.3 for those who received 7.5 microg of HA, 8.1 and 8.5 for those who received 15 microg of HA, and 14.8 and 12 for those who received 45 microg of HA. A > or =4-fold increase in titer was observed in 2% and 2% of subjects who received 3.75 microg of HA with or without AlOH, respectively; in 14% and 0% who received 7 microg of HA; in 14% and 13% who received 15 microg of HA; and in 33% and 25% who received 45 microg of HA. Addition of AlOH enhanced responses only for subjects who received 7.5 microg of HA, but responses in subjects who received 7.5 microg of HA without AlOH were unexpectedly low.
CONCLUSION
Overall, a meaningful beneficial effect of AlOH adjuvant was not observed.
TRIAL REGISTRATION
ClinicalTrials.gov identifier: NCT00296634 .
Topics: Adjuvants, Immunologic; Adolescent; Adult; Aluminum Hydroxide; Dose-Response Relationship, Immunologic; Double-Blind Method; Female; Hemagglutinins; Humans; Influenza A Virus, H5N1 Subtype; Influenza Vaccines; Male; Middle Aged
PubMed: 18808338
DOI: 10.1086/592172