Method for quantifying the Pasteurella multocida antigen adsorbed on aluminum hydroxide adjuvant in swine atrophic rhinitis vaccine.

Swine atrophic rhinitis is a disease caused by Pasteurella multocida and Bordetella bronchiseptica that affects pigs. Inactivated vaccines containing the toxins produced by Pasteurella multocida and Bordetella bronchiseptica have been widely used for the prevention of swine atrophic rhinitis. The efficacy of a vaccine is correlated with the amount of antigen present; however, the protective toxin of P. multocida bound to aluminum hydroxide, which is used as an adjuvant, can hinder the monitoring of the antigen concentration in the vaccine. This study assessed the applicability of a dot immunoassay as an antigen quantification method using monoclonal antibodies. This quantification method was able to detect the antigen with high specificity and sensitivity even when the antigen was bound to the adjuvant, and its application to vaccine products revealed a correlation between the amount of antigen present in the vaccine and the neutralizing antibody titers induced in pigs. The antigen quantification method presented in this study is a simple and sensitive assay capable of quantifying the amount of antigen present in a vaccine that can be used as an alternative quality control measure.

Lanthanum-modified pyroaurite as a geoengineering tool to simultaneously sink Microcystis cyanobacteria and immobilize phosphorus in eutrophic water.

Excessive phosphorus (P) in eutrophic water induces cyanobacterial blooms that aggravate the burden of in-situ remediation measures. In order to ensure better ecological recovery, Flock & Lock technique has been developed to simultaneously sink cyanobacteria and immobilize P but requires a combination of flocculent and P inactivation agent. Here we synthesized a novel lanthanum-modified pyroaurite (LMP), as an alternative for Flock & Lock of cyanobacteria and phosphorus at the background of rich humic acid and suspended solids. LMP shows a P adsorption capacity of 36.0 mg/g and nearly 100 % removal of chlorophyll-a (Chl-a), turbidity, UV254 and P at a dosage (0.3 g/L) much lower than the commercial analogue (0.5 g/L). The resultant sediment (98.2 % as immobile P) exhibits sound stability without observable release of P or re-growth of cyanobacteria over a 50-day incubation period. The use of LMP also constrains the release of toxic microcystins to 1.4 µg/L from the sunk cyanobacterial cells, outperforming the commonly used polyaluminum chloride (PAC). Similar Flock & Lock efficiency could also be achieved in real eutrophic water. The outstanding Flock & Lock performance of LMP is attributable to the designed La modification. During LMP treatment, La acts as not only a P binder by formation of LaPO4, but also a coagulant to create a synergistic effect with pyroaurite. The controlled hydrolysis of surface La(III) over pyroaurite aided the possible formation of La(III)-pyroaurite networking structure, which significantly enhanced the Flock & Lock process through adsorption, charge neutralization, sweep flocculation and entrapment. In the end, the preliminary economic analysis is performed. The results demonstrate that LMP is a versatile and cost-effective agent for in-situ remediation of eutrophic waters.

Molecular insights into effects of chemical conditioning on dissolved organic phosphorus transformation and bioavailability during sludge composting.

Phosphorus is enriched in waste activated sludge (WAS) during wastewater treatment, and organic phosphorus (OP) is a potential slow-release P fertilizer. The chemical coagulants used in sludge dewatering leave numerous residues in WAS that affect sludge composting. In this study, the effects of polyaluminum chloride (PAC) and polyferric sulfate (PFS) on the bioconversion of dissolved OP (DOP) during sludge composting were investigated. The results revealed that PFS conditioning promoted the transformation and bioavailability of DOP, whereas PAC conditioning inhibited. Results indicated that PFS conditioning enhanced the transformation of OP molecules in the thermophilic phase. Through oxidation and dehydrogenation reactions, 1-hydroxy-pentane-3,4-diol-5-phosphate and D-ribofuranose 5-phosphate with high bioactivity were generated in the PFS-conditioned compost. Enzymatic hydrolysis experiments further verified that PFS conditioning enhanced the DOP bioavailability in the compost, whereas PAC conditioning inhibited it. The study has provided molecular insights into the effects of chemical conditioning on DOP conversion during sludge composting.

Hymenoptera venom immunotherapy: Safety and efficacy of an accelerated induction regimen with depot aluminum adsorbed extracts.

Introduction: Hymenoptera venom immunotherapy (VIT) is the only therapy that protects patients with Hymenoptera venom allergy by preventing systemic reactions after a new sting. Various extracts for VIT are available and used. VIT administration consists of an induction phase and a maintenance phase. Depot preparations of Hymenoptera VIT extracts are typically used for cluster and conventional protocols, and the maintenance phase. Many patients with Hymenoptera allergy need to achieve tolerance quickly because of the high risk of re-sting and possible anaphylaxis. Objective: Our study aimed to show the safety and efficacy of an accelerated regimen with depot preparations on aluminum hydroxide by using relatively high starting doses in a heterogeneous group of patients. Methods: The research focused on a group of patients with a history of severe systemic reactions to Hymenoptera stings, with the necessity of swift immunization due to high occupational risks. Aluminum hydroxide depot extracts either of Vepula species or Apis mellifera extracts were used. Results: The induction protocol was started with the highest concentration of depot venom extract of 100,000 standard quality unit and was well tolerated by 19 of 20 patients. Onne patient presented with a mild systemic reaction during the accelerated induction schedule, which was promptly treated with intravenous steroids and intramuscular H1 antihistamine; when switched to a conventional induction protocol, he had a similar reaction but finally reached maintenance with an H1-antagonist premedication. Conclusion: If validated, the accelerated induction protocol by using depot aluminum adsorbed extracts with the highest concentration of venom from the beginning could offer a streamlined and accessible treatment modality for patients diagnosed with anaphylaxis from bee and wasp venoms in need of rapid desensitization.

Size-Optimized Layered Double Hydroxide Nanoparticles Promote Neural Progenitor Cells Differentiation of Embryonic Stem Cells Through the Regulation of M6A Methylation.

Purpose: The committed differentiation fate regulation has been a difficult problem in the fields of stem cell research, evidence showed that nanomaterials could promote the differentiation of stem cells into specific cell types. Layered double hydroxide (LDH) nanoparticles possess the regulation function of stem cell fate, while the underlying mechanism needs to be investigated. In this study, the process of embryonic stem cells (ESCs) differentiate to neural progenitor cells (NPCs) by magnesium aluminum LDH (MgAl-LDH) was investigated. Methods: MgAl-LDH with diameters of 30, 50, and 100 nm were synthesized and characterized, and their effects on the cytotoxicity and differentiation of NPCs were detected in vitro. Dot blot and MeRIP-qPCR were performed to detect the level of m6A RNA methylation in nanoparticles-treated cells. Results: Our work displayed that LDH nanoparticles of three different sizes were biocompatible with NPCs, and the addition of MgAl-LDH could significantly promote the process of ESCs differentiate to NPCs. 100 nm LDH has a stronger effect on promoting NPCs differentiation compared to 30 nm and 50 nm LDH. In addition, dot blot results indicated that the enhanced NPCs differentiation by MgAl-LDH was closely related to m6A RNA methylation process, and the major modification enzyme in LDH controlled NPCs differentiation may be the m6A RNA methyltransferase METTL3. The upregulated METTL3 by LDH increased the m6A level of Sox1 mRNA, enhancing its stability. Conclusion: This work reveals that MgAl-LDH nanoparticles can regulate the differentiation of ESCs into NPCs by increasing m6A RNA methylation modification of Sox1.

Hybrid response to SARS-CoV-2 and Neisseria meningitidis C after an OMV-adjuvanted immunization in mice and their offspring.

COVID-19, caused by SARS-CoV-2, and meningococcal disease, caused by Neisseria meningitidis, are relevant infectious diseases, preventable through vaccination. Outer membrane vesicles (OMVs), released from Gram-negative bacteria, such as N. meningitidis, present adjuvant characteristics and may confer protection against meningococcal disease. Here, we evaluated in mice the humoral and cellular immune response to different doses of receptor binding domain (RBD) of SARS-CoV-2 adjuvanted by N. meningitidis C:2a:P1.5 OMVs and aluminum hydroxide, as a combined preparation for these pathogens. The immunization induced IgG antibodies of high avidity for RBD and OMVs, besides IgG that recognized the Omicron BA.2 variant of SARS-CoV-2 with intermediary avidity. Cellular immunity showed IFN-γ and IL-4 secretion in response to RBD and OMV stimuli, demonstrating immunologic memory and a mixed Th1/Th2 response. Offspring presented transferred IgG of similar levels and avidity as their mothers. Humoral immunity did not point to the superiority of any RBD dose, but the group immunized with a lower antigenic dose (0.5 µg) had the better cellular response. Overall, OMVs enhanced RBD immunogenicity and conferred an immune response directed to N. meningitidis too.

Mesocosm study of PAC-modified clay effects on Karenia brevis cells and toxins, chemical dynamics, and benthic invertebrate physiology.

Modified clay compounds are used globally as a method of controlling harmful algal blooms, and their use is currently under consideration to control Karenia brevis blooms in Florida, USA. In 1400 L mesocosm tanks, chemical dynamics and lethal and sublethal impacts of MC II, a polyaluminum chloride (PAC)-modified kaolinite clay, were evaluated over 72 h on a benthic community representative of Sarasota Bay, which included blue crab (Callinectes sapidus), sea urchin (Lytechinus variegatus), and hard clam (Mercenaria campechiensis). In this experiment, MC II was dosed at 0.2 g L-1 to treat bloom-level densities of K. brevis at 1 × 106 cells L-1. Cell removal in MC II-treated tanks was 57% after 8 h and 95% after 48 h. In the water column, brevetoxin analogs BTx-1 and BTx-2 were found to be significantly higher in untreated tanks at 24 and 48 h, while in MC II-treated tanks, BTx-3 was found to be higher at 48 h and BTx-B5 was found to be higher at 24 and 48 h. In MC II floc, we found no significant differences in BTx-1 or BTx-2 between treatments for any time point, while BTx-3 was found to be significantly higher in the MC II-treated tanks at 48 and 72 h, and BTx-B5 was higher in MC II-treated tanks at 24 and 72 h. Among various chemical dynamics observed, it was notable that dissolved phosphorus was consistently significantly lower in MC II tanks after 2 h, and that turbidity in MC II tanks returned to control levels 48 h after treatment. Dissolved inorganic carbon and total seawater alkalinity were significantly reduced in MC II tanks, and partial pressure of CO2 (pCO2) was significantly higher in the MC II-only treatment after 2 h. In MC II floc, particulate phosphorus was found to be significantly higher in MC II tanks after 24 h. In animals, lethal and sublethal responses to MC II-treated K. brevis did not differ from untreated K. brevis for either of our three species at any time point, suggesting MC II treatment at this dosage has negligible impacts to these species within 72 h of exposure. These results appear promising in terms of the environmental safety of MC II as a potential bloom control option, and we recommend scaling up MC II experiments to field trials in order to gain deeper understanding of MC II performance and dynamics in natural waters.

Adjuvant-dependent impact of inactivated SARS-CoV-2 vaccines during heterologous infection by a SARS-related coronavirus.

Whole virus-based inactivated SARS-CoV-2 vaccines adjuvanted with aluminum hydroxide have been critical to the COVID-19 pandemic response. Although these vaccines are protective against homologous coronavirus infection, the emergence of novel variants and the presence of large zoonotic reservoirs harboring novel heterologous coronaviruses provide significant opportunities for vaccine breakthrough, which raises the risk of adverse outcomes like vaccine-associated enhanced respiratory disease. Here, we use a female mouse model of coronavirus disease to evaluate inactivated vaccine performance against either homologous challenge with SARS-CoV-2 or heterologous challenge with a bat-derived coronavirus that represents a potential emerging disease threat. We show that inactivated SARS-CoV-2 vaccines adjuvanted with aluminum hydroxide can cause enhanced respiratory disease during heterologous infection, while use of an alternative adjuvant does not drive disease and promotes heterologous viral clearance. In this work, we highlight the impact of adjuvant selection on inactivated vaccine safety and efficacy against heterologous coronavirus infection.

The impact of recycling polyaluminium chloride and anionic polyacrylamide water treatment residuals on heavy metal adsorption in soils: implications for stormwater bioretention systems.

Despite the high adsorption capacity of polyaluminum chloride and anionic polyacrylamide water treatment residuals (PAC-APAM WTRs) for Pb2+, Cd2+, Cu2+, and Zn2+, their influence on the adsorption behavior of heavy metals in traditional bioretention soil media remains unclear. This study investigated the impact of PAC-APAM WTRs at a 20% weight ratio on the adsorption removal of Pb2+, Cd2+, Cu2+, and Zn2+ in three types of soils. The results demonstrated improved heavy metal adsorption in the presence of PAC-APAM WTRs, with enhanced removal observed at higher pH levels and temperatures. The addition of PAC-APAM WTRs augmented the maximum adsorption capacity for Pb2+ (from 0.98 to 3.98%), Cd2+ (from 0.52 to 10.99%), Cu2+ (from 3.69 to 36.79%), and Zn2+ (from 2.63 to 13.46%). The Langmuir model better described the data in soils with and without PAC-APAM WTRs. The pseudo-second-order model more accurately described the adsorption process, revealing an irreversible chemical process, although qe demonstrated improvement with the addition of PAC-APAM WTRs. This study affirms the potential of PAC-APAM WTRs as an amendment for mitigating heavy metal pollution in stormwater bioretention systems. Further exploration of the engineering application of PAC-APAM WTRs, particularly in field conditions for the removal of dissolved heavy metals, is recommended.

A Pfs48/45-based vaccine to block Plasmodium falciparum transmission: phase 1, open-label, clinical trial.

BACKGROUND: The stalling global progress in malaria control highlights the need for novel tools for malaria elimination, including transmission-blocking vaccines. Transmission-blocking vaccines aim to induce human antibodies that block parasite development in the mosquito and mosquitoes becoming infectious. The Pfs48/45 protein is a leading Plasmodium falciparum transmission-blocking vaccine candidate. The R0.6C fusion protein, consisting of Pfs48/45 domain 3 (6C) and the N-terminal region of P. falciparum glutamate-rich protein (R0), has previously been produced in Lactococcus lactis and elicited functional antibodies in rodents. Here, we assess the safety and transmission-reducing efficacy of R0.6C adsorbed to aluminium hydroxide with and without Matrix-M™ adjuvant in humans. METHODS: In this first-in-human, open-label clinical trial, malaria-naïve adults, aged 18-55 years, were recruited at the Radboudumc in Nijmegen, the Netherlands. Participants received four intramuscular vaccinations on days 0, 28, 56 and 168 with either 30 µg or 100 µg of R0.6C and were randomised for the allocation of one of the two different adjuvant combinations: aluminium hydroxide alone, or aluminium hydroxide combined with Matrix-M1™ adjuvant. Adverse events were recorded from inclusion until 84 days after the fourth vaccination. Anti-R0.6C and anti-6C IgG titres were measured by enzyme-linked immunosorbent assay. Transmission-reducing activity of participants' serum and purified vaccine-specific immunoglobulin G was assessed by standard membrane feeding assays using laboratory-reared Anopheles stephensi mosquitoes and cultured P. falciparum gametocytes. RESULTS: Thirty-one participants completed four vaccinations and were included in the analysis. Administration of all doses was safe and well-tolerated, with one related grade 3 adverse event (transient fever) and no serious adverse events occurring. Anti-R0.6C and anti-6C IgG titres were similar between the 30 and 100 µg R0.6C arms, but higher in Matrix-M1™ arms. Neat participant sera did not induce significant transmission-reducing activity in mosquito feeding experiments, but concentrated vaccine-specific IgGs purified from sera collected two weeks after the fourth vaccination achieved up to 99% transmission-reducing activity. CONCLUSIONS: R0.6C/aluminium hydroxide with or without Matrix-M1™ is safe, immunogenic and induces functional Pfs48/45-specific transmission-blocking antibodies, albeit at insufficient serum concentrations to result in transmission reduction by neat serum. Future work should focus on identifying alternative vaccine formulations or regimens that enhance functional antibody responses. TRIAL REGISTRATION: The trial is registered with ClinicalTrials.gov under identifier NCT04862416.

Suitability of inorganic coagulants for algae-laden water treatment: Trade-off between algae removal and cell viability, aggregate properties and coagulant residue.

Inorganic coagulants could effectively precipitate algae cells but might increase the potential risks of cell damage and coagulant residue. This study was conducted to critically investigate the suitability of polyaluminum (PAC), FeCl3 and TiCl4 for algae-laden water treatment in terms of the trade-off between algal substance removal, cell viability, and coagulant residue. The results showed that an appropriate increase in coagulant dosage contributed to better coagulation performance but severe cell damage and a higher risk of intracellular organic matter (IOM) release. TiCl4 was the most destructive, resulting in 60.85% of the algal cells presenting membrane damage after coagulation. Intense hydrolysis reaction of Ti salts was favorable for the formation of larger and more elongated, dendritic structured flocs than Al and Fe coagulants. TiCl4 exhibited the lowest residue level and remained in the effluents mainly in colloidal form. The study also identified charge neutralization, chemisorption, enmeshment, and complexation as the dominant mechanisms for algae water coagulation by metal coagulants. Overall, this study provides the trade-off analyses between maximizing algae substance removal and minimizing potential damage to cell integrity and is practically valuable to develop the most suitable and feasible technique for algae-laden water treatment.

Enhancing pollutants removal in hospital wastewater: Comparative analysis of PAC coagulation vs. bio-contact oxidation, highlighting the impact of outdated treatment plants.

While the effectiveness of Poly-Aluminum Chloride (PAC) coagulation for pollutant removal has been documented across various wastewater scenarios, its specific application in hospital wastewater (HWW) treatment to remove conventional pollutants and hazardous genetic pollutants has not been studied. The research compared three hospital wastewater treatment plants (HWTPs) to address a knowledge gap, including the PAC coagulation-sodium hypochlorite disinfection process (PAC-HWTP), the biological contact oxidation-precipitation-sodium hypochlorite process (BCO-HWTP), and a system using outdated equipment with PAC coagulation (ODE-PAC-HWTP). Effluent compliance with national discharge standards is assessed, with BCO-HWTP meeting standards for direct or indirect discharge into natural aquatic environments. ODE-PAC-HWTP exceeds pretreatment standards for COD and BOD5 concentrations. PAC-HWTP effluent largely adheres to national pretreatment standards, enabling release into municipal sewers for further treatment. Metagenomic analysis reveals that PAC-HWTP exhibits higher removal efficiencies for antibiotic resistance genes, metal resistance genes, mobile genetic elements, and pathogens compared to BCO-HWTP and ODE-PAC-HWTP, achieving average removal rates of 45.13%, 57.54%, 80.61%, and 72.17%, respectively. These results suggests that when discharging treated HWW into municipal sewers for further processing, the use of PAC coagulation process is more feasible and cost-effective compared to BCO technologies. The analysis emphasizes the urgent need to upgrade outdated equipment HWTPs.

Poly I:C elicits broader and stronger humoral and cellular responses to a Plasmodium vivax circumsporozoite protein malaria vaccine than Alhydrogel in mice.

Malaria remains a global health challenge, necessitating the development of effective vaccines. The RTS,S vaccination prevents Plasmodium falciparum (Pf) malaria but is ineffective against Plasmodium vivax (Pv) disease. Herein, we evaluated the murine immunogenicity of a recombinant PvCSP incorporating prevalent polymorphisms, adjuvanted with Alhydrogel or Poly I:C. Both formulations induced prolonged IgG responses, with IgG1 dominance by the Alhydrogel group and high titers of all IgG isotypes by the Poly I:C counterpart. Poly I:C-adjuvanted vaccination increased splenic plasma cells, terminally-differentiated memory cells (MBCs), and precursors relative to the Alhydrogel-combined immunization. Splenic B-cells from Poly I:C-vaccinated mice revealed an antibody-secreting cell- and MBC-differentiating gene expression profile. Biological processes such as antibody folding and secretion were highlighted by the Poly I:C-adjuvanted vaccination. These findings underscore the potential of Poly I:C to strengthen immune responses against Pv malaria.

The orientation of CpG conjugation on aluminum oxyhydroxide nanoparticles determines the immunostimulatory effects of combination adjuvants.

In subunit vaccines, aluminum salts (Alum) are commonly used as adjuvants, but with limited cellular immune responses. To overcome this limitation, CpG oligodeoxynucleotides (ODNs) have been used in combination with Alum. However, current combined usage of Alum and CpG is limited to linear mixtures, and the underlying interaction mechanism between CpG and Alum is not well understood. Thus, we propose to chemically conjugate Alum nanoparticles and CpG (with 5' or 3' end exposed) to design combination adjuvants. Our study demonstrates that compared to the 3'-end exposure, the 5'-end exposure of CpG in combination adjuvants (Al-CpG-5') enhances the activation of bone-marrow derived dendritic cells (BMDCs) and promotes Th1 and Th2 cytokine secretion. We used the SARS-CoV-2 receptor binding domain (RBD) and hepatitis B surface antigen (HBsAg) as model antigens to demonstrate that Al-CpG-5' enhanced antigen-specific antibody production and upregulated cytotoxic T lymphocyte markers. Additionally, Al-CpG-5' allows for coordinated adaptive immune responses even at lower doses of both CpG ODNs and HBsAg antigens, and enhances lymph node transport of antigens and activation of dendritic cells, promoting Tfh cell differentiation and B cell activation. Our novel Alum-CPG strategy points the way towards broadening the use of nanoadjuvants for both prophylactic and therapeutic vaccines.

Evaluation of different types of adjuvants in a malaria transmission-blocking vaccine.

Adjuvants are critical components for vaccines, which enhance the strength and longevity of the antibody response and influence the types of immune response. Limited research has been conducted on the immunogenicity and protective efficacy of various adjuvants in malaria transmission-blocking vaccines (TBVs). In this study, we formulated a promising TBV candidate antigen, the P. berghei ookinete surface antigen PSOP25, with different types of adjuvants, including the TLR4 agonist monophosphoryl lipid A (MPLA), the TLR9 agonist cytosine phosphoguanosine oligodeoxynucleotides (CpG ODN 1826) (CpG), a saponin adjuvant QS-21, aluminum hydroxide (Alum), and two combination adjuvants MPLA + QS-21 and QS-21 + CpG. We demonstrated that adjuvanted vaccines results in elevated elicited antibody levels, increased proliferation of plasma cells, and efficient formation of germinal centers (GCs), leading to enhanced long-term protective immune responses. Furthermore, CpG group exhibited the most potent inhibition of ookinete formation and transmission-blocking activity. We found that the rPSOP25 with CpG adjuvant was more effective than MPLA, QS-21, MPLA + QS-21, QS-21 + CpG adjuvants in dendritic cells (DCs) activation and differentiation. Additionally, the CpG adjuvant elicited more rubust immune memory response than Alum adjuvant. CpG and QS-21 adjuvants could activate the Th1 response and promote the secretion of IFN-γ and TNF-α. PSOP25 induced a higher number of Tfh cells in splenocytes when combined with MPLA, CpG, and QS-21 + CpG; and there was no increase in these cell populations when PSOP25 was administered with Alum. In conclusion, CpG may confer enhanced efficacy for the rPSOP25 vaccine, as evidenced by the ability of the elicited antisera to induce protective immune responses and improved transmission-blocking activity.

Safety Assessment: a Comparative Analysis of Quantitative Content of Bacterial Endotoxins and Evaluation of Pyrogenicity of the Kazakhstan Vaccine QazCovid-in® against COVID-19.

We measured the levels of bacterial endotoxins in the bulk vaccine product (BVP) and finished vaccine QazCovid-in® and evaluated the effect of aluminum hydroxide (adjuvant) on the results of LAL test and pyrogenicity of samples in vivo (in rabbits receiving intravenous injection into the marginal ear vein). Administration of BVP with LPS resulted in a dose-dependent increase in body temperature in rabbits similar to that caused by LPS alone, which suggests that aluminum hydroxide in the vaccine did not affect the pyrogenic response in rabbits. Moreover, the LAL test showed that the aluminum hydroxide did not hinder LPS activity after serial dilution of samples.

Novel adjuvants in allergen-specific immunotherapy: where do we stand?

Type I hypersensitivity, or so-called type I allergy, is caused by Th2-mediated immune responses directed against otherwise harmless environmental antigens. Currently, allergen-specific immunotherapy (AIT) is the only disease-modifying treatment with the potential to re-establish clinical tolerance towards the corresponding allergen(s). However, conventional AIT has certain drawbacks, including long treatment durations, the risk of inducing allergic side effects, and the fact that allergens by themselves have a rather low immunogenicity. To improve AIT, adjuvants can be a powerful tool not only to increase the immunogenicity of co-applied allergens but also to induce the desired immune activation, such as promoting allergen-specific Th1- or regulatory responses. This review summarizes the knowledge on adjuvants currently approved for use in human AIT: aluminum hydroxide, calcium phosphate, microcrystalline tyrosine, and MPLA, as well as novel adjuvants that have been studied in recent years: oil-in-water emulsions, virus-like particles, viral components, carbohydrate-based adjuvants (QS-21, glucans, and mannan) and TLR-ligands (flagellin and CpG-ODN). The investigated adjuvants show distinct properties, such as prolonging allergen release at the injection site, inducing allergen-specific IgG production while also reducing IgE levels, as well as promoting differentiation and activation of different immune cells. In the future, better understanding of the immunological mechanisms underlying the effects of these adjuvants in clinical settings may help us to improve AIT.

Sequential hydrotalcite precipitation, microbial sulfate reduction and in situ hydrogen sulfide removal for neutral mine drainage treatment.

This study proposed and examined a new process flowsheet for treating neutral mine drainage (NMD) from an open-pit gold mine. The process consisted of three sequential stages: (1) in situ hydrotalcite (HT) precipitation; (2) low-cost carbon substrate driven microbial sulfate reduction; and (3) ferrosol reactive barrier for removing biogenic dissolved hydrogen sulfide (H2S). For concept validation, laboratory-scale columns were established and operated for a 140-days period with key process performance parameters regularly measured. At the end, solids recovered from various depths of the ferrosol column were analysed for elemental composition and mineral phases. Prokaryotic microbial communities in various process locations were characterised using 16S rRNA gene sequencing. Results showed that the Stage 1 HT-treatment substantially removed a range of elements (As, B, Ba, Ca, F, Zn, Si, and U) in the NMD, but not nitrate or sulfate. The Stage 2 sulfate reducing bioreactor (SRB) packed with 70 % (v/v) Eucalyptus woodchip, 1 % (w/v) ground (<1 mm) dried Typha biomass, and 10 % (w/v) NMD-pond sediment facilitated complete nitrate removal and stable sulfate removal of ca. 50 % (50 g-SO4 m-3 d-1), with an average H2S generation rate of 10 g-H2S m-3d-1. The H2S-removal performance of the Stage 3 ferrosol column was compared with a synthetic amorphous Fe-oxyhydroxide-amended sand control column. Although both columns facilitated excellent (95-100 %) H2S removal, the control column only enabled a further ca. 10 % sulfate reduction, giving an overall sulfate removal of 56 %. In contrast, the ferrosol enabled an extra 99.9 % sulfate reduction in the SRB effluent, leading to a near complete sulfate removal. Overall, the process successfully eliminated a range of metal/metalloid contaminants, nitrate, sulfate (2500 mg-SO4 L-1 in the NMD to <10 mg-SO4 L-1 in the final effluent) and H2S (>95 % removal). Further optimisation is required to minimise release of ferrous iron from the ferrosol barrier into the final effluent.

Ion-imprinted macroporous polyethyleneimine incorporated chitosan/layered hydrotalcite foams for the selective biosorption of U(VI) ions.

In order to prevent uranium pollution and recovery uranium resources, it was necessary to find a highly efficient adsorbent for radioactive wastewater treatment. Herein, U(VI) imprinted polyethyleneimine (PEI) incorporated chitosan/layered hydrotalcite composite foam (IPCL) was synthesized by combining ion-imprinting and freeze-drying techniques. IPCL has a high amino/imino content and an ultralight macroporous structure, making it capable of efficiently adsorbing U(VI) and easy to separate; Especially after ion-imprinting, vacancies matching the size of uranyl ions were formed, significantly improving U(VI) selectivity. The adsorption isotherms and adsorption kinetics were in accordance with the Freundlich model and PSO model respectively, indicating that heterogeneous adsorption of U(VI) by the adsorbents. The adsorption capacity of IPCL-2 for U(VI) reached 278.8. mg/g (under the conditions of optimal pH 5.0, temperature of 298 K, contact time of 2 h, and adsorbent dosage of 0.2 g/L), which is almost double of that for the non-imprinted foam (PCL-2, 138.2 mg/g), indicating that IPCL-2 can intelligently recognize U(VI). The heterogeneous adsorption mechanism of U(VI) by IPCL-2 involves complexation, ion-exchange and isomorphic substitution. The adsorption of U(VI) by IPCL-2 is spontaneous and endothermic. IPCL-2 has excellent adsorption performance for U(VI), and is a promising adsorbent for radioactive pollution control.

Evaluation of long-term immune response in cattle to botulism using a recombinant E. coli bacterin formulated with Montanide™ ISA 50 and aluminum hydroxide adjuvants.

Botulism is a severe disease caused by potent botulinum neurotoxins (BoNTs) produced by Clostridium botulinum. This disease is associated with high-lethality outbreaks in cattle, which have been linked to the ingestion of preformed BoNT serotypes C and D, emphasizing the need for effective vaccines. The potency of current commercial toxoids (formaldehyde-inactivated BoNTs) is assured through tests in guinea pigs according to government regulatory guidelines, but their short-term immunity raises concerns. Recombinant vaccines containing the receptor-binding domain have demonstrated potential for eliciting robust protective immunity. Previous studies have demonstrated the safety and effectiveness of recombinant E. coli bacterin, eliciting high titers of neutralizing antibodies against C. botulinum and C. perfringens in target animal species. In this study, neutralizing antibody titers in cattle and the long-term immune response against BoNT/C and D were used to assess the efficacy of the oil-based adjuvant compared with that of the aluminum hydroxide adjuvant in cattle. The vaccine formulation containing Montanide™ ISA 50 yielded significantly higher titers of neutralizing antibody against BoNT/C and D (8.64 IU/mL and 9.6 IU/mL, respectively) and induced an immune response that lasted longer than the response induced by aluminum, extending between 30 and 60 days. This approach represents a straightforward, cost-effective strategy for recombinant E. coli bacterin, enhancing both the magnitude and duration of the immune response to botulism.