Use of 3M-052-AF with Alum adjuvant in HIV trimer vaccine induces human autologous neutralizing antibodies.

Stabilized trimers preserving the native-like HIV envelope structure may be key components of a preventive HIV vaccine regimen to induce broadly neutralizing antibodies (bnAbs). We evaluated trimeric BG505 SOSIP.664 gp140 formulated with a novel TLR7/8 signaling adjuvant, 3M-052-AF/Alum, for safety, adjuvant dose-finding, and immunogenicity in a first-in-healthy adult (n = 17), randomized, and placebo-controlled trial (HVTN 137A). The vaccine regimen appeared safe. Robust, trimer-specific antibody, and B cell and CD4+ T cell responses emerged after vaccination. Five vaccinees developed serum autologous tier 2 nAbs (ID50 titer, 1:28-1:8647) after two to three doses targeting C3/V5 and/or V1/V2/V3 Env regions by electron microscopy and mutated pseudovirus-based neutralization analyses. Trimer-specific, B cell-derived monoclonal antibody activities confirmed these results and showed weak heterologous neutralization in the strongest responder. Our findings demonstrate the clinical utility of the 3M-052-AF/Alum adjuvant and support further improvements of trimer-based Env immunogens to focus responses on multiple broad nAb epitopes.

A recombinant N2 neuraminidase-based CpG 1018® adjuvanted vaccine provides protection against challenge with heterologous influenza viruses in mice and hamsters.

Recombinant influenza virus neuraminidase (NA) is a promising broadly protective influenza vaccine candidate. However, the recombinant protein alone is not sufficient to induce durable and protective immune responses and requires the coadministration of immunostimulatory molecules. Here, we evaluated the immunogenicity and cross-protective potential of a recombinant influenza virus N2 neuraminidase vaccine construct, adjuvanted with a toll-like receptor 9 (TLR9) agonist (CpG 1018® adjuvant), and alum. The combination of CpG 1018 adjuvant and alum induced a balanced and robust humoral and T-cellular immune response against the NA, which provided protection and reduced morbidity against homologous and heterologous viral challenges in mouse and hamster models. This study supports Syrian hamsters as a useful complementary animal model to mice for pre-clinical evaluation of influenza virus vaccines.

Poria cocos polysaccharide-loaded Alum Pickering emulsion as vaccine adjuvant to enhance immune responses.

Traditional Alum adjuvants mainly elicit a Th2 humoral immune response, but fail to generate a robust Th1 cellular immune response. However, the cellular immune response is essential for vaccination against cancer and a number of chronic infectious diseases, including human immunodeficiency virus infection and tuberculosis. In our previous study, we demonstrated that the polysaccharide from Poria cocos (PCP) has the potential to serve as an immunologic stimulant, enhancing both humoral and cellular immune responses. However, this effect was only observed at high concentrations. In this study, to enhance the immune-stimulation effect of PCP and modify the type of immune response elicited by Alum adjuvant, we successfully developed a Pickering emulsion delivery system (PCP-Al-Pickering) using PCP-loaded Alhydrogel particles as the stabilizer. After optimization, the Pickering emulsion exhibited excellent storage capacity and effectively adsorbed the PCP and antigen. As an adjuvant delivery system, the PCP-Al-Pickering emulsion facilitated the antigen uptake by macrophages, increased the recruitment of cells at injection sites, improved the activation of dendritic cells in draining lymph nodes, elicited a potent and durable antibody response, and promoted the activation of CD4+ and CD8+ T cells. Importantly, the PCP-Al-Pickering emulsion adjuvant elicited a balanced Th1 and Th2 immune response, in comparison to Alum adjuvant. The PCP-Al-Pickering emulsion may serve as a safe and promising adjuvant delivery system to enhance immune responses.

Biofunctional Textiles: Antioxidant and Antibacterial Finishings of Cotton with Propolis and Honey.

The growing activity in the textile industry has been demanding the search for new and innovative technologies to meet consumers' needs regarding more sustainable and ecological processes, with functionality receiving more attention. Bee products are known for their wide spectra of properties, including antioxidant and antibacterial activities. Propolis and honey are the most popular and used since ancient times for the most diverse applications due to their health benefits. With the increasing need for safer and more sustainable practices, the use of natural products for the functional finishing process can be a suitable alternative due to their safety and eco-friendly nature. For that, a biosolution, composed of a mixture of propolis and honey in water, was used to perform the functional finishing of cotton knits, both in the presence and in the absence of potassium alum as a chemical mordant. The fastness strength was also evaluated after three washing cycles. The antioxidant potential of the biosolution, assessed with the in vitro ABTS scavenging assay, provided textiles with the capacity to reduce more than 90% of the ABTS radical, regardless of the mordant presence and even after three washing cycles. Furthermore, biofunctional textiles decreased the growth of Bacillus subtilis, Propionibacterium acnes, Escherichia coli, and, particularly, Staphylococcus aureus cultures after 24 h of incubation with an increase in antibacterial activity when potassium alum was used. These findings show that bee products are promising and effective alternatives to be used in the textile industry to confer antioxidant and antibacterial properties to cotton textiles, thereby enhancing human health.

Nano-Sized Graphene Oxide Attenuates Ovalbumin/Alum-Induced Skin Inflammation by Down-Regulating Th2 Immune Responses in Balb/c Mice.

Graphene oxide (GO), a carbon-based material with oxygen-containing functional groups, can be applied in biomedicine for drug delivery, cancer therapy, and tissue regeneration. We have previously shown that nanoscale-sized graphene oxide (NGO), an oxidized graphene derivative, exhibits effective anti-inflammatory activity in a murine model of sepsis mediated by T helper (Th)1-promoting cytokines such as IFNγ and TNFα. However, whether NGO influences Th2-induced skin inflammation remains unclear. To address this issue, we employed an ovalbumin (OVA) plus aluminum hydroxide (Alum)-induced Th2-mediated skin inflammation model in conjunction with OVA-specific DO11.10 T cell receptor transgenic Balb/c mice. In vivo NGO injection upon OVA/Alum sensitization down-regulated OVA-elicited antigen-specific Th2 cells and GATA3-expressing Th2-type regulatory T cells. Next, we examined the effect of NGO injection on OVA/Alum-induced atopic dermatitis (AD)-like skin inflammation. NGO-injected mice exhibited significantly decreased Th2 disease phenotypes (e.g., a lower clinical score, decreased epidermal thickness and Th2 cell differentiation, and fewer infiltrated mast cells and basophils in skin lesions) compared with vehicle-injected control mice. Overall, our results suggest that NGOs are promising therapeutic materials for treating allergic diseases such as AD.

Characterization of Turbo, a TLR Ligand-based Adjuvant for Glycoconjugate Vaccines.

Many bacterial polysaccharide vaccines, including the typhoid Vi polysaccharide (ViPS) and tetravalent meningococcal polysaccharide conjugate (MCV4) vaccines, do not incorporate adjuvants and are not highly immunogenic, particularly in infants. I found that endotoxin, a TLR4 ligand in ViPS, contributes to the immunogenicity of typhoid vaccines. Because endotoxin is pyrogenic, and its levels are highly variable in vaccines, I developed monophosphoryl lipid A, a nontoxic TLR4 ligand-based adjuvant named Turbo. Admixing Turbo with ViPS and MCV4 vaccines improved their immunogenicity across all ages and eliminated booster requirement. To understand the characteristics of this adjuvanticity, I compared Turbo with alum. Unlike alum, which polarizes the response toward the IgG1 isotype, Turbo promoted Ab class switching to all IgG isotypes with affinity maturation; the magnitude of this IgG response is durable and accompanied by the presence of long-lived plasma cells in the mouse bone marrow. In striking contrast with the pathways employed by alum, Turbo adjuvanticity is independent of NLPR3, pyroptotic cell death effector Gasdermin D, and canonical and noncanonical inflammasome activation mediated by Caspase-1 and Caspase-11, respectively. Turbo adjuvanticity is primarily dependent on the MyD88 axis and is lost in mice deficient in costimulatory molecules CD86 and CD40, indicating that Turbo adjuvanticity includes activation of these pathways. Because Turbo formulations containing either monophosphoryl lipid A or TLR2 ligands, Pam2CysSerLys4, and Pam3CysSerLys4 help generate Ab response of all IgG isotypes, as an adjuvant Turbo can improve the immunogenicity of glycoconjugate vaccines against a wide range of bacterial pathogens whose elimination requires appropriate IgG isotypes.

Using a novel bio-based cationic flocculant for food industry wastewater treatment.

Wastewater from the food industry is considered harmful to human health and aquatic life, as well as polluting water and soil. This research is centered around finding an affordable and easy physicochemical method for dealing with waste generated by the food industry. To accomplish this goal, a new bio-based flocculant called 4-benzyl-4-(2-oleamidoethylamino-2-oxoethyl) morpholin-4-ium chloride was created using sustainable sources, specifically crude olive pomace oil. Its chemical structure was confirmed using various spectroscopic techniques such as FTIR, 1H-NMR, mass spectra, and 13C-NMR. This new bio-based cationic flocculant was combined with alum to act as a coagulant in the waste treatment process. Also, a study was conducted to determine the optimal conditions for the coagulation-flocculation process parameters, namely, pH and alum dosage, on COD and removal efficiency. The results showed that the optimal conditions for flocculation were achieved at pH 5.8, with 680 mg/L alum and 10 mg/L of commercial flocculant dose compared to only 5 mg/L of a new bio-based cationic flocculant. A comparison was made between the new bio-cationic flocculant and a commercial CTAB one for treating wastewater in the food industry. The study found that the new bio-based cationic flocculant was more effective in reducing the chemical oxygen demand, achieving a reduction of 61.3% compared to 54.6% for using a commercial cationic flocculant. Furthermore, using a new bio-based cationic flocculant costs only 0.49 $/g, which is less than the present cationic flocculant, which costs 0.93 $/g. The adoption of this new flocculant provides a sustainable alternative to existing industrial wastewater treatment processes.

Combining Killed Vaccine Candidate with Different Adjuvants to Determine Prophylactic Potential against Leishmaniasis.

Visceral Leishmaniasis is a serious public health problem caused by Leishmania species parasites. Approximately 500 thousand people get Visceral Leishmaniasis (VL) every year. An effective and reliable vaccine against the disease has still not been formulated. Choosing the right adjuvant is important to increase immunogenicity in vaccines prepared with total antigens. In this study, we investigate the ideal adjuvant for use in vaccine formulations against VL. For this purpose, Leishmania antigens (FTLA) obtained from L. infantum parasites by the freeze-thaw method and three different adjuvants (alum-saponin and calcium phosphate) were used. The effectiveness of the formulations was investigated in vitro by cell viability analysis and determination of nitric oxide and cytokine production abilities in J774 macrophage cells. According to the study results, it was determined that formulations prepared with calcium phosphate produced 72% more NO and approximately 7.2 times more IL-12 cytokine. The results obtained showed that calcium phosphate salts can be used as ideal adjuvants in vaccine research against leishmaniasis.

Boosting the immune response in COVID-19 vaccines via an Alum:CpG complex adjuvant.

Selecting appropriate adjuvants is crucial for developing an effective vaccine. However, studies on the immune responses triggered by different adjuvants in COVID-19 inactivated vaccines are scarce. Herein, we evaluated the efficacy of Alum, CpG HP021, Alum combined with CpG HP021 (Alum/CpG), or MF-59 adjuvants with COVID-19 inactivated vaccines in K18-hACE2 mice, and compared the different immune responses between K18-hACE2 and BALB/c mice. In K18-hACE2 mice, the Alum/CpG group produced a 6.5-fold increase in anti-receptor-binding domain (RBD) IgG antibody titers compared to the Alum group, and generated a comparable level of antibodies even when the antigen amount was reduced by two-thirds, possibly due to the significant activation of germinal center (GC) structures in the central region of the spleen. Different adjuvants induced a variety of binding antibody isotypes. CpG HP021 and Alum/CpG were biased towards Th1/IgG2c, while Alum and MF-59 were biased toward Th2/IgG1. Cytokines IFN-γ, IL-2, and TNF-α were significantly increased in the culture supernatants of splenocytes specifically stimulated in the Alum/CpG group. The antibody responses in BALB/c mice were similar to those in K18-hACE2 mice, but with lower levels of neutralizing antibodies (NAbs). Notably, the Alum/CpG-adjuvanted inactivated vaccine induced a higher number of T cells secreting IFN-γ and IL-2, increased the percentage of effector memory T (TEM) cells among CD8+ T cells, and effectively protected K18-hACE2 mice from Delta variant challenge. Our results showed that Alum/CpG complex adjuvant significantly enhanced the immune response to inactivated COVID-19 antigens and could induce a long-lasting immune response.

Synthesis, application and molecular docking of modified cellulose with diaminoguanidine as complexing agent for selective separation of Cu (II), Cd (II) and Hg (II) ions from alum sample.

A new modified cellulose with diaminoguanidine (Cel-Gua) synthesized for specific recovery of Cu (II), Cd (II), and Hg (II) from the alum sample. Cellulose was silanized by 3-chloropropyltrimethoxysilane and then was modified with diaminoguanidine to obtain N-donor chelating fibers. Fourier transform-infrared spectroscopy, scanning electron microscopy, X-ray diffraction, zeta potential, electrons disperse X-ray analysis, elemental analyses (C, H and N), and thermogravimetric analysis were used for characterization. Factors influencing the adsorption were thoroughly examined. Under the optimal conditions, the Cel-Gua sorbent displayed maximum adsorption capacities of 94.33, 112.10 and 95.78 mg/g for Cu (II), Cd (II), and Hg (II), respectively. The sorption process of metal ions is equipped by kinetic model PSO and Langmuir adsorption isotherm. The calculated thermodynamic variables confirmed that the adsorption of Cu (II), Cd (II) and Hg (II) by Cel-Gua sorbent is a spontaneous and exothermic process. In our study, we used the molecular operating environment software to conduct molecular docking simulations on the Cel-Gua compound. The results of the docking simulations showed that the Cel-Gua compound displayed greater potency and a stronger affinity for the Avr2 effector protein derived from Fusarium oxysporum, a fungal plant pathogen (code 5OD4). The adsorbent was stable for 7 cycles, thus allowing its safe reutilization.

Relationship between protein conformational stability and its immunogenicity when administering antigens to mice using adjuvants-Analysis employed the CH2 domain in human antibodies.

Antigen-presenting cells (APCs) play a crucial role in the immune system by breaking down antigens into peptide fragments that subsequently bind to major histocompatibility complex (MHC) molecules. Previous studies indicate that stable proteins can impede CD4+ T cell stimulation by hindering antigen processing and presentation. Conversely, certain proteins require stabilization in order to activate the immune response. Several factors, including the characteristics of the protein and the utilization of different adjuvants in animal experiments, may contribute to this disparity. In this study, we investigated the impact of adjuvants on antigen administration in mice, specifically focusing on the stability of the CH2 domain. Consequently, the CH2 domain induced a stronger IgG response in comparison to the stabilized one when using Alum and PBS (without adjuvant). On the other hand, animal experiment using Freund's adjuvant showed the opposite results. These findings indicate the significance of considering the intrinsic conformational stability of a protein when eliciting its immunogenicity, particularly within the context of vaccine development.

Green hybrid coagulants for water treatment: An innovative approach using alum and bentonite clay combined with eco-friendly plant materials for batch and column adsorption.

Textile industries contribute to water pollution through synthetic dye discharge. This study explores the use of natural bio-coagulants to remove acid dyes from wastewater, investigating factors like pH, coagulant dose, dye concentration, contact time, and temperature for optimal results. The optimum pH and coagulants capabilities of (CAAPP, CAAPH, CBAGL, CBAPP and CBAPH) were 3 (49.6 mg/g), 3 (42.5 mg/g), 3 (38.9 mg/g), 4 (35.7 mg/g), 4 (34.1 mg/g), and 4 (29.4 mg/g) respectively, while treating of selected BRF-221 dyes from water solution. The acidic range (3-4) was found to have the best pH for the maximal coagulation, and the optimal dose were found to be 0.05 g/50 mL. The equilibrium was attained within 45-60 min for all coagulants. After 60 min of shaking, the maximum coagulation capacities (21.9, 21.02, 16.5, 27.9, 25.3, and 23.4 mg/g) of several coagulant composites (CAAGL, CAAPP, CAAPH, CBAGL, CBAPP, CBAPH) were determined. The initial BRF-221 dye concentration in the range of 10-200 mg/L was considered as optimum for gaiting maximum elimination of dye using different coagulants. At a dye value of 100 mg/L of BRF-221, maximal coagulation capacities CAAGL (179.19 mg/g), CAAPP (166.06 mg/g), CAAPH (141.60 mg/g), and CBAGL (126.49 mg/g), CBAPP (113.9 mg/g), CBAPH (93.08 mg/g) were attained. The study found 35 °C to be the optimal temperature for maximum acid dye removal using bio-coagulants. Increasing temperature reduced coagulation capacity, indicating an exothermic process. Freundlich and Langmuir isotherms showed suitability for pseudo-first-order and pseudo-second-order kinetics in biosorption. Thermodynamic parameters were assessed for process feasibility. Effective coagulants demonstrated sensitivity to electrolyte variations. In column studies, adjusting parameters achieved maximum coagulation efficiency for removing BRF-221 dyes. The study successfully applied optimal parameters to remove real textile effluents at a practical scale. SEM, FT-IR, BET and XRD characterized coagulants, providing insights into stability and morphology.

Removal of acephate and methamidophos from water: Coagulation and adsorptive treatment approaches.

Pesticides has transformed the agricultural industry, primarily by enhancing productivity. However, the indiscriminate use of such compounds can adversely affect human health and disrupt ecosystem balance. Limited knowledge exists regarding the removal of these compounds from water, particularly for organophosphate pesticides when employing conventional treatment technologies. Therefore, this study aimed to assess the removal of acephate (ACE) and methamidophos (MET) - considered priority pesticides in Brazil - from waters with high and low turbidity during the clarification process carried out with aluminum sulfate (AS) and ferric chloride (FC), either alone or combined with powdered activated carbon (PAC) adsorption. All water samples were submitted to solid phase extraction (SPE C18 cartridges) prior to acephate and methamidophos analysis by HPLC MS/MS. The clarification process with either AS or FC coagulant did not efficiently remove acephate or methamidophos and maximum average removal (27 %) was observed with waters of high turbidity when using ferric chloride as coagulant. Addition of mineral PAC was also ineffective for removing both pesticides. However, the use of vegetable PAC (10 mg/L) resulted in better removal percentages, up to 80%, but only for methamidophos. The limited removal rates were attributed to the high hydrophilicity of acephate and methamidophos, along with their neutral charge at coagulation pH. These factors hinder the interaction of such organophosphorus pesticides with the flocs formed during coagulation as well as with PAC surface.

Aluminosilicate and zeolitic materials synthesis using alum sludge from water treatment plants: Challenges and perspectives.

Alum sludge (AS) is a by-product generated from drinking water treatment and produced in large amounts around the world. Its chemical composition makes this waste an emerging alternative source of silicon and aluminum for aluminosilicates or zeolite material production, which can add value to residues and contribute to the circular economy process on a global scale. In this sense, and considering the scarcity of information about AS, this review shows data collection about AS in different countries, including generation, chemical composition, and disposal information. The reuse of AS is discussed based on circular economy and the environmental gains derived from such approaches are highlighted, including the possibility of utilization with other residues (e.g., ash, bioproducts, etc). Moreover, this review shows and discusses the benefits and challenges of AS reuse in the synthesis process and how it can be a sustainable raw material for aluminosilicates and zeolite synthesis. The most common conditions (conventional or non-conventional) in zeolite synthesis from AS are mentioned and advantages, limitations and trends are discussed. The discussions and data presented can improve the AS management and reuse legislations, which certainly will collaborate with sustainable AS use and circular economy processes.

Enhanced removal of lead and zinc by a 3D aluminium sulphate-functionalised graphene aerogel as an effective adsorption system.

The discharge of heavy metals into the environment has adversely affected the aquatic ecosystem due to their toxic and non-biodegradable nature. In this research, a three-dimensional graphene oxide/carboxymethylcellulose/aluminium sulphate (GOCAS) aerogel was synthesised and evaluated as a novel means for lead and zinc removal. The GOCAS aerogel was prepared via ice-templating of graphene oxide with carboxymethylcellulose and aluminium sulphate as the crosslinking and functionalisation additives. Characterisation of the aerogel by various analytical techniques confirmed the successful integration of the chemical additives. The hydroxyl and sulphate groups in the aerogel were found to participate in the adsorption of both metals. The equilibrium of lead adsorption was found to correlate well to the Freundlich isotherm, while zinc adsorption fitted closely the Langmuir isotherm. The kinetic adsorption behaviour of both metals was best described as pseudo-second-order. The interactive influences of concentration, temperature, contact time and adsorbent dose on the metal removal were explored by a central composite design, and the optimum adsorption capacity for lead was determined to be 138.7 mg/g at a GOCAS dose of 20 mg, initial concentration of 100 mg/L, temperature of 50 °C and contact time of 45 min. The optimum adsorption capacity for zinc was 52.69 mg/g at 30 mg, 65 mg/L, 45 °C and 40 min. Furthermore, regeneration studies with hydrochloric acid eluant were successfully conducted for up to four adsorption-desorption cycles. Overall, this work demonstrates that GOCAS aerogel is a viable nanosorbent for the adsorption of lead and zinc from water systems.

Augmenting vaccine efficacy: Tailored immune strategy with alum-stabilized Pickering emulsion.

BACKGROUND: The achievement of optimal vaccine efficacy is contingent upon the collaborative interactions between T and B cells in adaptive immunity. Although multiple immunization strategies have been proposed, there is a notable scarcity of comprehensive investigations pertaining to enhance immune effects through immune strategy adjustments for individual vaccine. METHODS: The hierarchically structured aluminum hydroxide microgel-stabilized Pickering emulsion (ASPE) was prepared by ultrasonic method. This study explored the influence of the immune strategy of ASPE to immune responses, including antigen exposure pattern, adjuvants and antigen dosage, and administration interval. RESULTS: The findings revealed that external antigen adsorption facilitated increased exposure of antigen epitopes, leading to elevated IgG titers and secretion of cytokines such as interferon-gamma (IFN-γ) or interleukin-4 (IL-4). Additionally, even a low dose (1 µg/dose) of antigens of ASPE boosted sufficient neutralizing antibody levels and memory T cells compared to high-dose antigens, which consistent with the adjuvant dosage effect. Furthermore, maintaining a 4-week immunization interval yielded optimal levels of antigen-specific IgG titers in both short-term and long-term scenarios, as compared to intervals of 2, 3, and 5 weeks. A consistent trend was observed in the proliferation of memory B cells, reaching a superior level at the 4-week interval, which could enhance protection against viral re-infection. CONCLUSION: Tailoring immunization strategies for specific vaccines has emerged as powerful driver in maximizing vaccine efficacy and eliciting robust immune responses, thereby presenting cutting-edge approaches to enhanced vaccination.

The coagulation process for enveloped and non-enveloped virus removal in turbid water: Removal efficiencies, mechanisms and its application to SARS-CoV-2 Omicron BA.2.

The coagulation process has a high potential as a treatment method that can handle pathogenic viruses including emerging enveloped viruses in drinking water treatment process which can lower infection risk through drinking water consumption. In this study, a surrogate enveloped virus, bacteriophage Փ6, and surrogate non-enveloped viruses, including bacteriophage MS-2, T4, ՓX174, were used to evaluate removal efficiencies and mechanisms by the conventional coagulation process with alum, poly­aluminum chloride, and ferric chloride at pH 5, 7, and 9 in turbid water. Also, treatability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a recent virus of global concern by coagulation was evaluated as SARS-CoV-2 can presence in drinking water sources. It was observed that an increase in the coagulant dose enhanced the removal efficiency of turbidity and viruses, and the condition that provided the highest removal efficiency of enveloped and non-enveloped viruses was 50 mg/L of coagulants at pH 5. In addition, the coagulation process was more effective for enveloped virus removal than for the non-enveloped viruses, and it demonstrated reduction of SARS-CoV-2 Omicron BA.2 over 0.83-log with alum. According to culture- and molecular-based assays (qPCR and CDDP-qPCR), the virus removal mechanisms were floc adsorption and coagulant inactivation. Through inactivation with coagulants, coagulants caused capsid destruction, followed by genome damage in non-enveloped viruses; however, damage to a lipid envelope is suggested to contribute to a great extend for enveloped virus inactivation. We demonstrated that conventional coagulation is a promising method for controlling emerging and re-emerging viruses in drinking water.

Phosphate adsorption on dried alum sludge: Modeling and application to treatment of dairy effluents.

This study evaluates Alum sludge from drinking water treatment plants for the efficient and cost-effective removal of phosphates from aqueous solutions. Extensive characterization and batch experiments have established that optimal phosphate removal was achieved with a sludge dosage of 20 g L-1 (at an initial phosphate concentration of 100 mg L-1), a pH of 5, a temperature of 23 °C, and a stirring speed of 200 rpm. These conditions significantly reduced phosphate levels, ensuring compliance with legal discharge limits. The Langmuir isotherm, pseudo-second-order kinetic and intraparticle diffusion models best described the adsorption process, highlighting the spontaneous and endothermic nature of the phenomenon. The sludge effectively reduced phosphate concentrations to acceptable levels when applied to dairy effluents. This study underscores the potential of Alum sludge as a viable solution for phosphate management in environmental cleanup efforts.

Structure-Activity Relationships toward the Identification of a High-Potency Selective Human Toll-like Receptor-7 Agonist.

Toll-like receptor (TLR)-7 agonists are immunostimulatory vaccine adjuvants. A systematic structure-activity relationship (SAR) study of TLR7-active 1-benzyl-2-butyl-1H-imidazo[4,5-c]quinolin-4-amine led to the identification of a potent hTLR7-specific p-hydroxymethyl IMDQ 23 with an EC50 value of 0.22 µM. The SAR investigation also resulted in the identification of TLR7 selective carboxamide 12 with EC50 values of 0.32 µM for hTLR7 and 18.25 µM for hTLR8. In the vaccination study, TLR7-specific compound 23 alone or combined with alum (aluminum hydroxide wet gel) showed adjuvant activity for a spike protein immunogen in mice, with enhanced anti-spike antibody production. Interestingly, the adjuvant system comprising carboxamide 12 and alum showed prominent adjuvant activity with high levels of IgG1, IgG2b, and IgG2c in immunized mice, confirming a balanced Th1/Th2 response. In the absence of any apparent toxicity, the TLR7 selective agonists in combination with alum may make a suitable vaccine adjuvant.

Hypothetical adhesin CAM87009.1 formulated in alum or biogenic silver nanoparticles protects mice from lethal infection by multidrug-resistant Acinetobacter baumannii.

Due to its antimicrobial resistance characteristics, the World Health Organization (WHO) classifies A. baumannii as one of the critical priority pathogens for the development of new therapeutic strategies. Vaccination has been approached as an interesting strategy to overcome the lack of effective antimicrobials and the long time required to develop and approve new drugs. In this study, we aimed to evaluate as a vaccine the hypothetical adhesin protein CAM87009.1 in its recombinant format (rCAM87009.1) associated with aluminum hydroxide (Alhydrogel®) or biogenic silver nanoparticles (bio-AgNP) as adjuvant components against lethal infection by A. baumannii MDR strain. Both vaccine formulations were administered in three doses intramuscularly in BALB/c murine models and the vaccinated animals were tested in a challenge assay with A. baumannii MDR strain (DL100). rCAM87009.1 protein associated with both adjuvants was able to protect 100 % of animals challenged with the lethal strain during the challenge period. After the euthanasia of the animals, no A. baumannii colonies were detected in the lungs of animals vaccinated with the rCAM87009.1 protein in both formulations. Since the first immunization, high IgG antibody titers were observed (1:819,200), with results being statistically similar in both vaccine formulations evaluated. rCAM87009.1 associated with both adjuvants was capable of inducing at least one class of isotypes associated with the processes of neutralization (IgG2b and IgA for bio-AgNP and Alhydrogel®, respectively), opsonization (IgG1 in both vaccines) and complement activation (IgM and IgG3 for bio-AgNP and Alhydrogel®, respectively). Furthermore, reduced tissue damage was observed in animals vaccinated with rCAM87009.1 + bio-AgNP when compared to animals vaccinated with Alhydrogel®. Our results indicate that the rCAM87009.1 protein associated with both bio-AgNP and Alhydrogel® are combinations capable of promoting immunity against infections caused by A. baumannii MDR. Additionally, we demonstrate the potential of silver nanoparticles as alternative adjuvant molecules to the use of aluminum salts.