Investigation of the Hepatitis-B Vaccine's Immune Response in a Non-Alcoholic Fatty Liver Disease Mouse Model.

This study aimed to investigate the immunogenicity of the hepatitis B virus (HBV) vaccine by applying a normal and high-dose hepatitis B virus vaccination program in the mice modeling of non-alcoholic fatty liver disease (NAFLD). NAFLD was induced in mouse livers via diet. At the 10-week mark, both groups were divided into 3 subgroups. While the standard dose vaccination program was applied on days 0, 7, and 21, two high-dose programs were applied: one was applied on days 0 and 7, and the other was applied on days 0, 7, and 21. All mice were euthanized. Blood samples from anti-HB titers; T follicular helper, T follicular regulatory, CD27+, and CD38+ cells; and the liver, spleen, and thymus were taken for histopathologic evaluation. NAFLD subgroups receiving high doses showed higher hepatocyte ballooning scores than normal-dose subgroup. There were differences in CD27+ and CD27+CD38+ cells in animals fed on different diets, without any differences or interactions in terms of vaccine protocols. In the NAFLD group, a negative correlation was observed between anti-HB titers and T helper and CD27+ cells, while a positive correlation was observed with CD38+ cells. NAFLD induced changes in immune parameters in mice, but there was no difference in vaccine efficacy among the applied vaccine protocols. Based on this study's results, high-dose vaccination protocols are not recommended in cases of NAFLD, as they do not enhance efficacy and may lead to increased liver damage.

Analysis of Immunobiological Properties of Recombinant Streptococcus pneumoniae Pneumolysin.

We compared the immunogenicity of recombinant S. pneumoniae pneumolysin (rPly) when administered with and without Al(OH)3 adjuvant, and evaluated the protective properties of recombinant protein in the active defense experiment. It was shown that double immunization with rPly+Al(OH)3 increases the levels of IgG antibodies in comparison with the control (p<0.01), while triple immunization results in a more significant increase in IgG antibody levels (p<0.001). Double immunization with rPly without Al(OH)3 does not induce a significant increase in antibody levels in comparison with the control, while triple immunization results in a slight but significant increase in antibody levels (p<0.05). The active defense test proved the protective activity of rPly against S. pneumoniae serotype 3 at intranasal infection.

Rate-Dependent Tensile Properties of Aluminum-Hydroxide-Enhanced Ethylene Propylene Diene Monomer Coatings for Solid Rocket Motors.

Quasi-static and dynamic tensile tests on aluminum-hydroxide-enhanced ethylene propylene diene monomer (EPDM) coatings were conducted using a universal testing machine and a Split Hopkinson Tension Bar (SHTB) over a strain rate range of 10-3 to 103 s-1. This comprehensive study explored the tensile performance of enhanced EPDM coatings in solid rocket motors. The results demonstrated a significant impact of strain rate on the mechanical properties of EPDM coatings. To capture the hyperelastic and viscoelastic characteristics of EPDM coatings at large strains, the Ogden hyperelastic model was used to replace the standard elastic component to develop an enhanced Zhu-Wang-Tang (ZWT) nonlinear viscoelastic constitutive model. The model parameters were fitted using a particle swarm optimization (PSO) algorithm. The improved constitutive model's predictions closely matched the experimental data, accurately capturing stress-strain responses and inflection points. It effectively predicts the tensile behavior of aluminum-hydroxide-enhanced EPDM coatings within a 20% strain range and a wide strain rate range.

Aluminum hydroxide and immunostimulatory glycolipid adjuvant combination for enhanced COVID-19 subunit vaccine immunogenicity.

Protein-based subunit vaccines like RBD-Fc are promising tools to fight COVID-19. RBD-Fc fuses the receptor-binding domain (RBD) of the SARS-CoV-2 virus spike protein with the Fc region of human IgG1, making it more immunogenic than RBD alone. Earlier work showed that combining RBD-Fc with iNKT cell agonists as adjuvants improved neutralizing antibodies but did not sufficiently enhance T cell responses, a limitation RBD-Fc vaccines share with common adjuvants. Here we demonstrate that aluminum hydroxide combined with α-C-GC, a C-glycoside iNKT cell agonist, significantly improved the RBD-Fc vaccine's induction of RBD-specific T-cell responses. Additionally, aluminum hydroxide with α-GC-CPOEt, a phosphonate diester derivative, synergistically elicited more robust neutralizing antibodies. Remarkably, modifying αGC with phosphate (OPO3H2) or phosphonate (CPO3H2) to potentially enhance aluminum hydroxide interaction did not improve efficacy over unmodified αGC with aluminum hydroxide. These findings underscore the straightforward yet potent potential of this approach in advancing COVID-19 vaccine development and provide insights for iNKT cell-based immunotherapy.

Clinical Characteristics, Therapeutic Options, and Outcomes in Hyperphosphatemic Tumoral Calcinosis: A Systematic Review.

This systematic review was performed to understand better the myriad presentations, various therapeutic options, response to therapy, and its clinical outcomes in hyperphosphatemic tumoral calcinosis (HTC). Full texts were selected according to strict inclusion criteria. All case reports of HTC wherein baseline phosphate was measured, treatment offered was mentioned, and information on follow-up and response to therapy that were available were included. A total of 43 of 188 eligible studies (N = 63 patients) met the inclusion criteria. A list of desired data was extracted and graded for methodological quality. A total of 63 individuals (Males = 33) were included from the 43 eligible case studies. The median age of the patients was 18 (IQR 8-32) years. The most frequently involved sites were the hip/gluteal region (34/63; 53.9%) followed by the elbow/forearm (26/63; 41.2%), and the shoulder (18/63; 28.5%). Three patients had conjunctival calcific deposits. The mean (SD) phosphate was 6.9 (1.1) mg/dL. Among the subjects, 36/63 (57.1%) underwent surgical excision with some form of medical therapy. Two patients underwent only surgical excision (2.1%). One patient was maintained on follow-up (1.6%) and 24/63 (38.1%) patients were treated with medical measures. The median (IQR) follow-up duration was 3 (1-9) years. Regression or reduction in lesion size was reported in 19/63 (30.2%) subjects; 20/63 (31.7%) showed progression, 24/63 (38.1%) had features of stable disease, and mortality was reported in 3 patients (4.7%). We report for the first time a detailed description of the clinical and therapeutic response of HTC. A combination of medical measures aimed at lowering serum phosphate appears to be the cornerstone of treatment, although clinical responses may vary.

Identifying transcriptomic profiles in ovine spleen after repetitive vaccination.

Aluminum hydroxide has long been employed as a vaccine adjuvant for its safety profile, although its precise mechanism of action remains elusive. In this study, we investigated the transcriptomic responses in sheep spleen following repetitive vaccination with aluminum adjuvanted vaccines and aluminum hydroxide alone. Notably, this work represents the first exploration of the sheep spleen transcriptome in such conditions. Animals were splitted in 3 treatment groups: vaccine group, adjuvant alone group and control group. A total of 18 high-depth RNA-seq libraries were sequenced, resulting in a rich dataset which also allowed isoform-level analysis. The comparisons between vaccine-treated and control groups (V vs C) as well as between vaccine-treated and adjuvant-alone groups (V vs A) revealed significant alterations in gene expression profiles, including protein coding genes and long non-coding RNAs. Among the differentially expressed genes, many were associated with processes such as endoplasmic reticulum (ER) stress, immune response and cell cycle. The analysis of co-expression modules further indicated a correlation between vaccine treatment and genes related to ER stress and unfolded protein response. Surprisingly, adjuvant-alone treatment had little impact on the spleen transcriptome. Additionally, the role of alternative splicing in the immune response was explored. We identified isoform switches in genes associated with immune regulation and inflammation, potentially influencing protein function. In conclusion, this study provides valuable insights into the transcriptomic changes in sheep spleen following vaccination with aluminum adjuvanted vaccines and aluminum hydroxide alone. These findings shed light on the molecular mechanisms underlying vaccine-induced immune responses and emphasize the significance of antigenic components in aluminum adjuvant mechanism of action. Furthermore, the analysis of alternative splicing revealed an additional layer of complexity in the immune response to vaccination in a livestock species.

Photo-switchable Collectors for the Flotation of Lithium Aluminate for the Recycling of the Critical Raw Material Lithium.

Flotation of the mineral lithium aluminate by application of the natural product punicine from Punica granatum and some derivatives as collectors is examined. Punicines, 1-(2',5'-dihydroxyphenyl)-pyridinium compounds, are switchable molecules whose properties can be changed reversibly. They exist as cations, neutral mesomeric betaines, anions, and dianions depending on the pH. In light, they form radicals. Five punicine derivatives were prepared which possess ß-methyl, ß-chlorine, γ-tert.-butyl, and γ-acetyl groups attached to the pyridinium ring, and a pyrogallol derivative. On the other hand, LiAlO2 reacts with water to give species such as LiAl2(OH)7 on its surface. Flotations were performed applying the punicines in daylight (3000 lux), in darkness (<40 lux) and under UV-irradiation (4500 lux, 390-400 nm). The pH of the suspension, the collector's concentration, the conditioning time as well as the flotation time were varied. The recovery rates strongly depend on these parameters. For example, the recovery rate of lithium aluminate was increased by 116 % on changing the lighting condition from daylight to darkness, when the pyrogallol derivative of punicine was applied. UV, FTIR, TGA and zeta potential measurements as well as DFT calculations were performed in order to gain insight into the chemistry of punicines on the surface of LiAlO2 and LiAl2(OH)7 in water which influence the flotation's results.

Bilateral Acute Posterior Multifocal Placoid Pigment Epitheliopathy With Bacillary Layer Detachment Following Sinopharm COVID-19 Vaccination: A Case Report.

Various ocular manifestations associated with COVID-19 and vaccines, affecting both the anterior and posterior segments of the eye have been documented in the literature. In this report, we present the case of a 25-year-old male who complained of sudden-onset blurred vision and metamorphopsia in both eyes one day after receiving the second dose of the Sinopharm COVID-19 vaccine. The visual loss was painless, with no reported flashes or floaters. The patient had no significant medical or surgical history, no history of trauma, and no drug intake. Upon ocular examination, the best-corrected visual acuity was 6/60 (Snellen chart) in both eyes. The anterior segments appeared unremarkable, while fundoscopy revealed multiple yellowish-white subretinal lesions at the posterior pole of both eyes. Spectral domain optical coherence tomography (SD-OCT) confirmed the presence of subretinal fluid (SRF) with neurosensory detachment in each eye, along with bacillary layer detachment (BALAD). There were no signs of inflammation in the vitreous cavity. A diagnosis of acute posterior multifocal plaque pigment epitheliopathy (APMPPE) was established. The patient was prescribed nepafenac 0.1% drops to be instilled three times a day in both eyes and was advised to return for a follow-up examination in two weeks. At the follow-up visit, the patient's vision had improved to 6/9 in the right eye and 6/6 in the left eye, with most of the SRF absorbed. Unilateral APMPPE with BALAD has been mentioned in the literature following various COVID-19 vaccinations, but, to the best of our knowledge, this is the first case report where bilateral APMPPE with BALAD is reported. This case emphasizes the importance of a thorough eye examination for individuals experiencing ocular symptoms after receiving the COVID-19 vaccine.

Recovery of aluminum oxide and iron oxide from aluminum electrolysis iron-rich cover material and preparation of aluminum fluoride.

In aluminum electrolysis, the iron-rich cover material is formed on the cover material and the steel rod connecting the carbon anode. Due to the high iron content in the iron-rich cover material, it differs from traditional cover material and thus requires harmless recycling and treatment. A process was proposed and used in this study to recovery F, Al, and Fe elements from the iron-rich cover material. This process involved aluminum sulfate solution leaching for fluorine recovery and alkali-acid synergistic leaching for α-Al2O3 and Fe2O3 recovery were obtained. The optimal leaching rates for F, Na, Ca, Fe, and Si were 93.92, 96.25, 94.53, 4.48, and 28.87%, respectively. The leaching solution and leaching residue were obtained. The leaching solution was neutralized to obtain the aluminum hydroxide fluoride hydrate (AHFH, AlF1.5(OH)1.5·(H2O)0.375). AHFH was calcined to form a mixture of AlF3 and Al2O3 with a purity of 96.14%. The overall recovery rate of F in the entire process was 92.36%. Additionally, the leaching residue was sequentially leached with alkali and acid to obtain the acid leach residue α-Al2O3. The pH of the acid-leached solution was adjusted to produce a black-brown precipitate, which was converted to Fe2O3 under a high-temperature calcination, and the recovery rate of Fe in the whole process was 94.54%. Therefore, this study provides a new method for recovering F, Al, and Fe in iron-rich cover material, enabling the utilization of aluminum hazardous waste sources.

Key Process Parameters Study for the Fill Finish of Vaccines Containing Aluminum Hydroxide Adjuvant.

Vaccine manufacturing is one of the most challenging and complex processes in pharmaceutical industry, and the process control strategy is critical for the safety, effectiveness, and consistency of a vaccine. The efficacy of aluminum salt adjuvant on vaccines strongly depends on its physicochemical properties, such as size, structure, surface charge, etc. However, stresses during the vaccine manufacturing may affect the stability of adjuvant. In this study, the impacts of cold/thermal stress, autoclaving, pumping, mixing, and filling shear stress on the physicochemical properties of aluminum hydroxide (AH) adjuvant were evaluated as part of the manufacturing process development. The results showed that the autoclaving process would slightly influence the structure and properties of the investigated AH adjuvant, but thermal incubation at 2-8 °C, 25 °C and 40 °C for 4 weeks did not. However, -20 °C freezing AH adjuvant led to the adjuvant agglomeration and rapid sedimentation. For the high shear stress study with mixing at 500 rpm in a 1-L mixing bag and pumping at 220 rpm for up to 24 h, the average particle dimension of the bulk AH adjuvant decreased, along with decreasing protein adsorption ratio. The studies indicate that various stresses during manufacturing process could affect the structure and physicochemical properties of AH adjuvant, which calls for more attention on the control of adjuvant process parameters during manufacturing.

Growth of Floc Structure and Subsequence Compaction into Smaller Granules through Breakup and Rearrangement of Aluminum Flocs in a Constant Laminar Shear Flow.

We have constructed an outer-cylinder-rotating Couette device for high-speed shear flow in laminar flow conditions and visualized the structure formation and subsequent rearrangement of PACl (flocculant made of aluminum hydroxide gel) and kaolinite flocs by visible light imaging. In a previous report, we analyzed the case of relatively low shear rate (G-value = 29 1/s) and confirmed that the flocculation process could be separated into two stages: a floc growth stage and a breakup/rearrangement stage. Once the large bulky flocs that reached the maximum size appeared, they rearranged and densified through structural fracture and rearrangement. In this report, this process was further investigated by conducting experiments under two different high shear rates (58 and 78 1/s) at which breakup and rearrangement became more pronounced, and three different aluminum kaolinite ratios (ALT ratios) that were over and under the optimum dosage (neutralization point by Zeta potential). Visualization results confirmed that, during the growth stage, the flocculation rate could be approximated by a scaling relationship between floc size and elapsed time, which depended on the ALT ratio. After reaching the maximum size, the floc rapidly became compact and dense following adsorption of the gel, incorporating fine fragments from erosion breakup. The over and under dosages created a lot of fragments of erosion breakup, but less so in the optimum dosage. In the optimum ALT ratio, fragments did not remain because they were incorporated into the flocs and densified, and the floc size was thought to be maintained. The floc circularity distribution peaked at around 0.6 and 1, suggesting that the flocs were spherical in shape due to erosion breakup.

Autoclave-Induced Changes in the Physicochemical Properties and Antigen Adsorption of Aluminum Adjuvants.

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.

Aluminum hydroxide nanoparticle adjuvants can reduce the inflammatory response more efficiently in a mouse model of allergic asthma than traditional aluminum hydroxide adjuvants.

Traditional aluminum hydroxide is widely used as a vaccine adjuvant. Despite its favorable safety profile, it can cause an inflammatory response at the injection sites. However, multiple studies have shown that aluminum hydroxide nanoparticles have more potent adjuvant activity than their traditional aluminum hydroxide counterparts as antigen carriers; it has also been found that the local inflammation caused by aluminum hydroxide nanoparticle adjuvants is milder than that of other adjuvants. The aim of the present study was to compare the degree of inflammatory response between the aluminum hydroxide nanoparticle adjuvants and the traditional aluminum hydroxide adjuvants in the desensitization treatment of a mouse model of house dust mite (HDM)-induced allergic asthma. Mice were sensitized intraperitoneally with HDM. Subcutaneous desensitization was performed with PBS, traditional aluminum hydroxide adjuvants and aluminum hydroxide nanoparticle adjuvants. The mice were challenged and subsequently euthanized. The skin tissue at the local injection sites was assessed and specific indices were measured, such as the response of specific immunoglobulins, the airway hyper-responsiveness (AHR), and the inflammation in the bronchoalveolar lavage and lung tissues. Early hypersensitivity responses were suppressed in mice treated with subcutaneous immunotherapy (SCIT). Both traditional aluminum hydroxide-SCIT and aluminum hydroxide nanoparticle-SCIT could inhibit AHR. However, aluminum hydroxide nanoparticle-SCIT was able to significantly inhibit the secretion of eosinophils in the lung tissue and the production of type 2 cytokine Interleukin (IL)-5 in blood compared with the corresponding effects noted by traditional aluminum hydroxide adjuvants. Moreover, the aluminum hydroxide nanoparticle group reduced the inflammatory response at the local injection site. Collectively, the data indicated that allergen-specific immunotherapy using aluminum hydroxide nanoparticle adjuvants reduces lung and local inflammation compared with traditional aluminum hydroxide adjuvants.

Integrated Circular Economy Model System for Direct Lithium Extraction: From Minerals to Batteries Utilizing Aluminum Hydroxide.

Aluminum hydroxide, an abundant mineral found in nature, exists in four polymorphs: gibbsite, bayerite, nordstrandite, and doyleite. Among these polymorphs gibbsite, bayerite, and commercially synthesized amorphous aluminum hydroxide have been investigated as sorbent materials for lithium extraction from sulfate solutions. The amorphous form of Al(OH)3 exhibits a reactivity higher than that of the naturally occurring crystalline polymorphs in terms of extracting Li+ ions. This study employed high-temperature oxide melt solution calorimetry to explore the energetics of the sorbent polymorphs. The enthalpic stability order was measured to be gibbsite > bayerite > amorphous Al(OH)3. The least stable form, amorphous Al(OH)3, undergoes a spontaneous reaction with lithium, resulting in the formation of a stable layered double hydroxide phase. Consequently, amorphous Al(OH)3 shows promise as a sorbent material for selectively extracting lithium from clay mineral leachate solutions. This research demonstrates the selective direct extraction of Li+ ions using amorphous aluminum hydroxide through a liquid-solid lithiation reaction, followed by acid-free delithiation and relithiation processes, achieving an extraction efficiency of 86%, and the maximum capacity was 37.86 mg·g-1 in a single step during lithiation. With high selectivity during lithiation and nearly complete recoverability of the sorbent material during delithiation, this method presents a circular economy model. Furthermore, a life cycle analysis was conducted to illustrate the environmental advantages of replacing the conventional soda ash-based precipitation process with this method, along with a simple operational cost analysis to evaluate reagent and fuel expenses.

Immunization of mice with chimeric protein-loaded aluminum hydroxide and selenium nanoparticles induces reduction of Brucella melitensis infection in mice.

Purpose: Due to the many problems with commercially available vaccines, the production of effective vaccines against brucellosis is a necessity. The aim of this study was to evaluate the immune responses caused by the chimeric protein consisting of trigger factor, Bp26, and Omp31 (TBO) along with aluminum hydroxide (AH/TBO) and selenium (Se/TBO) nanoparticles (NPs) as adjuvants in mouse model. Materials and Methods: Recombinant antigen expression was induced in Escherichia coli BL21 (DE3) bacteria using IPTG (isopropyl-d-1-thiogalactopyranoside). Purification and characterization of recombinant protein was conducted through NiFe3O4 NPs, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and Western blot. NP characteristics, including morphology and particle size, were measured in vitro. The recombinant TBO was loaded on to AH and Se NPs and were administered subcutaneously. After mice immunization, measurement of antibody titter and protection assay was performed. Results: The average sizes of AH and Se NPs were about 60 nm and 150 nm, respectively. The enzyme-linked immunosorbent assay results showed that the serum of mice immunized by subcutaneous injection with both nanovaccines produced significant immunoglobulin G (IgG) responses against the chimeric antigen. The results of TBO-specific IgG isotype (IgG2a/IgG1) analysis showed that both AH and Se NPs induced a type to T-helper immune response. In addition, the results of the challenge with the pathogenic strain of Brucella melitensis 16M showed that vaccinated mice with AH/TBO NPs indicated a higher reduction of bacterial culture than immunized mice with Se/TBO NPs and TBO alone. Conclusion: The results showed that AH NPs carrying chimeric antigen can be a promising vaccine candidate against brucellosis by producing protective immunity.

Systematic Evaluation of the Distribution of Immune Cells following Subcutaneous Administration of Haemophilus Influenzae Type B Vaccine to Mice.

The Haemophilus influenzae type B (Hib) conjugate vaccine is the most effective way to prevent Hib infection in infants and young children, and it is designed to induce the production of antibodies against polyribosylribitol phosphate (PRP) to protect babies from infection. However, the mechanism of immunity induced by the Hib vaccine is not fully understood. Recently, with the development of the combination diphtheria and tetanus toxoids and acellular pertussis vaccines (DTaP), increasing numbers of manufacturers have begun to develop DTaP-based combination vaccines, like the combination vaccine diphtheria and tetanus toxoids and acellular pertussis and Hib conjugate vaccine (DTaP-Hib), which contains adjuvants. However, the Hib vaccine does not contain adjuvants. It was theorized that the Hib antigen has poor compatibility with aluminum adjuvants for unclear reasons. Therefore, understanding the mechanism of the Hib-vaccine-induced immune response and the influence of adjuvants on the Hib vaccine is of great significance. In this paper, we immunized BalBc mice with either the Hib vaccine or the Hib vaccine that adsorbs aluminum adjuvants (Hib-Al). Here, we analyzed the anti-PRP antibody level and immune response of different cells using cell and cytokine levels. We found that the Hib vaccine could induce a humoral and cellular immune response, and the Hib-Al vaccine could induce greater quantities of IFN-γ, IL-4, and IL-6 and more antigen-specific antibodies through B cells, Th1, Th2, and ILC3s in the spleen. Together, our findings demonstrate the serologic responses and immune response in terms of cell and cytokine levels induced by the Hib vaccine, and they also imply that the addition of aluminum hydroxide adjuvant could enhance the function of the Hib vaccine, which preliminarily reveals the mechanism of immune response induced by the Hib-related vaccine.

A TLR9 agonist synergistically enhances protective immunity induced by an Alum-adjuvanted H7N9 inactivated whole-virion vaccine.

Antigen sparing is an important strategy for pandemic vaccine development because of the limitation of worldwide vaccine production during disease outbreaks. However, several clinical studies have demonstrated that the current aluminum (Alum)-adjuvanted influenza vaccines fail to sufficiently enhance immune responses to meet licensing criteria. Here, we used pandemic H7N9 as a model virus to demonstrate that a 10-fold lower amount of vaccine antigen combined with Alum and TLR9 agonist can provide stronger protective effects than using Alum as the sole adjuvant. We found that the Alum/CpG 1018 combination adjuvant could induce more robust virus-specific humoral immune responses, including higher total IgG production, hemagglutination-inhibiting antibody activity, and neutralizing antibody titres, than the Alum-adjuvanted formulation. Moreover, this combination adjuvant shifted the immune response toward a Th1-biased immune response. Importantly, the Alum/CpG 1018-formulated vaccine could confer better protective immunity against H7N9 challenge than that adjuvanted with Alum alone. Notably, the addition of CpG 1018 to the Alum-adjuvanted H7N9 whole-virion vaccine exhibited an antigen-sparing effect without compromising vaccine efficacy. These findings have significant implications for improving Alum-adjuvanted influenza vaccines using the approved adjuvant CpG 1018 for pandemic preparedness.

Aluminum Adjuvants-'Back to the Future'.

Aluminum-based adjuvants will continue to be a key component of currently approved and next generation vaccines, including important combination vaccines. The widespread use of aluminum adjuvants is due to their excellent safety profile, which has been established through the use of hundreds of millions of doses in humans over many years. In addition, they are inexpensive, readily available, and are well known and generally accepted by regulatory agencies. Moreover, they offer a very flexible platform, to which many vaccine components can be adsorbed, enabling the preparation of liquid formulations, which typically have a long shelf life under refrigerated conditions. Nevertheless, despite their extensive use, they are perceived as relatively 'weak' vaccine adjuvants. Hence, there have been many attempts to improve their performance, which typically involves co-delivery of immune potentiators, including Toll-like receptor (TLR) agonists. This approach has allowed for the development of improved aluminum adjuvants for inclusion in licensed vaccines against HPV, HBV, and COVID-19, with others likely to follow. This review summarizes the various aluminum salts that are used in vaccines and highlights how they are prepared. We focus on the analytical challenges that remain to allowing the creation of well-characterized formulations, particularly those involving multiple antigens. In addition, we highlight how aluminum is being used to create the next generation of improved adjuvants through the adsorption and delivery of various TLR agonists.

Eu(III) and Am(III) adsorption on aluminum (hydr)oxide minerals: surface complexation modeling.

Americium is a highly radioactive actinide element found in used nuclear fuel. Its adsorption on aluminum (hydr)oxide minerals is important to study for at least two reasons: (i) aluminum (hydr)oxide minerals are ubiquitous in the subsurface environment and (ii) bentonite clays, which are proposed engineered barriers for the geologic disposal of used nuclear fuel, have the same ≡AlOH sites as aluminum (hydr)oxide minerals. Surface complexation modeling is widely used to interpret the adsorption behavior of heavy metals on mineral surfaces. While americium sorption is understudied, multiple adsorption studies for europium, a chemical analog, are available. In this study we compiled data describing Eu(III) adsorption on three aluminum (hydr)oxide minerals-corundum (α-Al2O3), γ-alumina (γ-Al2O3) and gibbsite (γ-Al(OH)3)-and developed surface complexation models for Eu(III) adsorption on these minerals by employing diffuse double layer (DDL) and charge distribution multisite complexation (CD-MUSIC) electrostatic frameworks. We also developed surface complexation models for Am(III) adsorption on corundum (α-Al2O3) and γ-alumina (γ-Al2O3) by employing a limited number of Am(III) adsorption data sourced from literature. For corundum and γ-alumina, two different adsorbed Eu(III) species, one each for strong and weak sites, were found to be important regardless of which electrostatic framework was used. The formation constant of the weak site species was almost 10,000 times weaker than the formation constant for the corresponding strong site species. For gibbsite, two different adsorbed Eu(III) species formed on the single available site type and were important for the DDL model, whereas the best-fit CD-MUSIC model for Eu(III)-gibbsite system required only one Eu(III) surface species. The Am(III)-corundum model based on the CD-MUSIC framework had the same set of surface species as the Eu(III)-corundum model. However, the log K values of the surface reactions were different. The best-fit Am(III)-corundum model based on the DDL framework had only one site type. Both the CD-MUSIC and the DDL model developed for Am(III)-γ-alumina system only comprised of one site type and the formation constant of the corresponding surface species was ~ 500 times stronger and ~ 700 times weaker than the corresponding Eu(III) species on the weak and the strong sites, respectively. The CD-MUSIC model for corundum and both the DDL and the CD-MUSIC models for γ-alumina predicted the Am(III) adsorption data very well, whereas the DDL model for corundum overpredicted the Am(III) adsorption data. The root mean square of errors of the DDL and CD-MUSIC models developed in this study were smaller than those of two previously-published models describing Am(III)-γ-alumina system, indicating the better predictive capacity of our models. Overall, our results suggest that using Eu(III) as an analog for Am(III) is practical approach for predicting Am(III) adsorption onto well-characterized minerals.

Aluminum hydroxide exposure induces neurodevelopmental impairment in hESC-derived cerebral organoids.

Aluminum (Al) has been classified as a cumulative environmental pollutant that endangers human health. There is increasing evidence to suggest the toxic effects of Al, but the specific action on human brain development remains unclear. Al hydroxide (Al(OH)3), the most common vaccine adjuvant, is the major source of Al and poses risks to the environment and early childhood neurodevelopment. In this study, we explored the neurotoxic effect of 5 µg/ml or 25 µg/ml Al(OH)3 for six days on neurogenesis by utilizing human cerebral organoids from human embryonic stem cells (hESCs). We found that early Al(OH)3 exposure in organoids caused a reduction in the size, deficits in basal neural progenitor cell (NPC) proliferation, and premature neuron differentiation in a time and dose-dependent manner. Transcriptomes analysis revealed a markedly altered Hippo-YAP1 signaling pathway in Al(OH)3 exposed cerebral organoid, uncovering a novel mechanism for Al(OH)3-induced detrimental to neurogenesis during human cortical development. We further identified that Al(OH)3 exposure at day 90 mainly decreased the production of outer radial glia-like cells(oRGs) but promoted NPC toward astrocyte differentiation. Taken together, we established a tractable experimental model to facilitate a better understanding of the impact and mechanism of Al(OH)3 exposure on human brain development.