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1.
Harmful Algae ; 134: 102609, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38705612

RESUMEN

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.


Asunto(s)
Hidróxido de Aluminio , Dinoflagelados , Floraciones de Algas Nocivas , Toxinas Marinas , Animales , Dinoflagelados/efectos de los fármacos , Dinoflagelados/fisiología , Dinoflagelados/química , Arcilla/química , Bivalvos/fisiología , Bivalvos/efectos de los fármacos , Erizos de Mar/fisiología , Erizos de Mar/efectos de los fármacos , Florida , Braquiuros/fisiología , Braquiuros/efectos de los fármacos , Mercenaria/efectos de los fármacos , Mercenaria/fisiología , Silicatos de Aluminio/farmacología , Silicatos de Aluminio/química
2.
Hum Vaccin Immunother ; 20(1): 2346963, 2024 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-38745461

RESUMEN

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.


Asunto(s)
Anticuerpos Antivirales , COVID-19 , Inmunoglobulina G , Neisseria meningitidis , SARS-CoV-2 , Animales , Ratones , Inmunoglobulina G/sangre , Neisseria meningitidis/inmunología , Femenino , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , COVID-19/prevención & control , COVID-19/inmunología , SARS-CoV-2/inmunología , Adyuvantes Inmunológicos/administración & dosificación , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Inmunidad Celular , Inmunidad Humoral , Ratones Endogámicos BALB C , Infecciones Meningocócicas/prevención & control , Infecciones Meningocócicas/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Adyuvantes de Vacunas/administración & dosificación , Hidróxido de Aluminio/administración & dosificación , Hidróxido de Aluminio/inmunología , Inmunización/métodos , Afinidad de Anticuerpos , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/inmunología , Vacunas Meningococicas/inmunología , Vacunas Meningococicas/administración & dosificación , Memoria Inmunológica , Células TH1/inmunología
3.
Nat Commun ; 15(1): 3738, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38702297

RESUMEN

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.


Asunto(s)
Hidróxido de Aluminio , Vacunas contra la COVID-19 , COVID-19 , SARS-CoV-2 , Vacunas de Productos Inactivados , Animales , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Femenino , COVID-19/prevención & control , COVID-19/inmunología , COVID-19/virología , Ratones , Vacunas de Productos Inactivados/inmunología , SARS-CoV-2/inmunología , Hidróxido de Aluminio/administración & dosificación , Modelos Animales de Enfermedad , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes de Vacunas , Anticuerpos Antivirales/inmunología , Ratones Endogámicos BALB C , Humanos , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/inmunología
4.
J Hazard Mater ; 471: 134314, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38640668

RESUMEN

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.


Asunto(s)
Hidróxido de Aluminio , Supervivencia Celular , Compuestos Férricos , Floculación , Titanio , Purificación del Agua , Purificación del Agua/métodos , Hidróxido de Aluminio/química , Supervivencia Celular/efectos de los fármacos , Floculación/efectos de los fármacos , Compuestos Férricos/química , Titanio/química , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/toxicidad , Cloruros/química
5.
J Hazard Mater ; 471: 134340, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38640670

RESUMEN

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.


Asunto(s)
Hospitales , Oxidación-Reducción , Hipoclorito de Sodio , Aguas Residuales , Contaminantes Químicos del Agua , Aguas Residuales/química , Hipoclorito de Sodio/química , Contaminantes Químicos del Agua/química , Eliminación de Residuos Líquidos/métodos , Desinfección/métodos , Purificación del Agua/métodos , Polímeros/química , Hidróxido de Aluminio
6.
Water Sci Technol ; 89(6): 1570-1582, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38557719

RESUMEN

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.


Asunto(s)
Resinas Acrílicas , Hidróxido de Aluminio , Metales Pesados , Purificación del Agua , Cadmio , Suelo , Adsorción , Plomo , Metales Pesados/análisis , Purificación del Agua/métodos
7.
Front Immunol ; 15: 1331474, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38650939

RESUMEN

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.


Asunto(s)
Hidróxido de Aluminio , Anticuerpos Antiprotozoarios , Inmunoglobulina G , Vacunas contra la Malaria , Malaria Vivax , Plasmodium vivax , Poli I-C , Proteínas Protozoarias , Animales , Vacunas contra la Malaria/inmunología , Proteínas Protozoarias/inmunología , Proteínas Protozoarias/genética , Ratones , Plasmodium vivax/inmunología , Anticuerpos Antiprotozoarios/inmunología , Poli I-C/inmunología , Malaria Vivax/inmunología , Malaria Vivax/prevención & control , Hidróxido de Aluminio/inmunología , Inmunoglobulina G/inmunología , Inmunoglobulina G/sangre , Femenino , Adyuvantes Inmunológicos , Inmunidad Humoral , Inmunidad Celular , Ratones Endogámicos BALB C
8.
BMC Med ; 22(1): 170, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38649867

RESUMEN

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.


Asunto(s)
Vacunas contra la Malaria , Malaria Falciparum , Glicoproteínas de Membrana , Plasmodium falciparum , Proteínas Protozoarias , Adolescente , Adulto , Animales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Adyuvantes Inmunológicos/administración & dosificación , Hidróxido de Aluminio/administración & dosificación , Anticuerpos Antiprotozoarios , Vacunas contra la Malaria/inmunología , Vacunas contra la Malaria/administración & dosificación , Malaria Falciparum/prevención & control , Malaria Falciparum/transmisión , Malaria Falciparum/inmunología , Países Bajos , Plasmodium falciparum/inmunología , Proteínas Protozoarias/inmunología
9.
Biomaterials ; 308: 122569, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38626556

RESUMEN

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.


Asunto(s)
Adyuvantes Inmunológicos , Hidróxido de Aluminio , Óxido de Aluminio , Células Dendríticas , Antígenos de Superficie de la Hepatitis B , Nanopartículas , Oligodesoxirribonucleótidos , Adyuvantes Inmunológicos/farmacología , Animales , Nanopartículas/química , Células Dendríticas/efectos de los fármacos , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Oligodesoxirribonucleótidos/química , Oligodesoxirribonucleótidos/farmacología , Antígenos de Superficie de la Hepatitis B/inmunología , Antígenos de Superficie de la Hepatitis B/metabolismo , Hidróxido de Aluminio/química , Hidróxido de Aluminio/farmacología , Ratones , Ratones Endogámicos C57BL , Femenino , Citocinas/metabolismo , Compuestos de Alumbre/química , Compuestos de Alumbre/farmacología
10.
Int Immunopharmacol ; 131: 111817, 2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38460299

RESUMEN

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.


Asunto(s)
Vacunas contra la Malaria , Malaria , Humanos , Adyuvantes Inmunológicos , Compuestos de Alumbre , Hidróxido de Aluminio , Malaria/prevención & control , Oligodesoxirribonucleótidos
11.
Int J Biol Macromol ; 266(Pt 1): 131113, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38531524

RESUMEN

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.


Asunto(s)
Hidróxido de Aluminio , Quitosano , Hidróxido de Magnesio , Polietileneimina , Uranio , Uranio/química , Polietileneimina/química , Quitosano/química , Adsorción , Hidróxido de Aluminio/química , Cinética , Hidróxido de Magnesio/química , Porosidad , Concentración de Iones de Hidrógeno , Purificación del Agua/métodos , Temperatura , Iones/química
12.
Sci Total Environ ; 926: 171537, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38460684

RESUMEN

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.


Asunto(s)
Hidróxido de Aluminio , Sulfuro de Hidrógeno , Hidróxido de Magnesio , ARN Ribosómico 16S , Nitratos , Sulfatos/química , Reactores Biológicos
13.
Front Immunol ; 15: 1348305, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38464539

RESUMEN

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.


Asunto(s)
Desensibilización Inmunológica , Hipersensibilidad , Humanos , Adyuvantes Inmunológicos/uso terapéutico , Alérgenos , Hidróxido de Aluminio , Adyuvantes Farmacéuticos
14.
Bull Exp Biol Med ; 176(4): 452-456, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38491256

RESUMEN

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.


Asunto(s)
COVID-19 , Vacunas , Animales , Conejos , Lipopolisacáridos , Hidróxido de Aluminio/análisis , Kazajstán , COVID-19/prevención & control , Endotoxinas
15.
Vaccine ; 42(8): 1980-1992, 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38388238

RESUMEN

Two malaria transmission-blocking vaccine (TBV) candidates, R0.6C and ProC6C, have completed preclinical development including the selection of adjuvants, Alhydrogel® with or without the saponin based adjuvant Matrix-M™. Here, we report on the final drug product (formulation) design of R0.6C and ProC6C and evaluate their safety and biochemical stability in preparation for preclinical and clinical pharmacy handling. The point-of-injection stability studies demonstrated that both the R0.6C and ProC6C antigens are stable on Alhydrogel in the presence or absence of Matrix-M for up to 24 h at room temperature. As this is the first study to combine Alhydrogel and Matrix-M for clinical use, we also evaluated their potential interactions. Matrix-M adsorbs to Alhydrogel, while not displacing the > 95 % adsorbed protein. The R0.6C and ProC6C formulations were found to be safe and well tolerated in repeated dose toxicity studies in rabbits generating high levels of functional antibodies that blocked infection of mosquitoes. Further, the R0.6C and ProC6C drug products were found to be stable for minimally 24 months when stored at 2-8 °C, with studies ongoing through 36 months. Together, this data demonstrates the safety and suitability of the L. lactis expression system as well as supports the clinical testing of the R0.6C and ProC6C malaria vaccine candidates in First-In-Human clinical trials.


Asunto(s)
Vacunas contra la Malaria , Malaria Falciparum , Animales , Conejos , Hidróxido de Aluminio , Anticuerpos Antiprotozoarios , Antígenos de Protozoos , Vacunas contra la Malaria/efectos adversos , Malaria Falciparum/prevención & control , Plasmodium falciparum , Proteínas Protozoarias
16.
Microb Pathog ; 189: 106596, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38395317

RESUMEN

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.


Asunto(s)
Toxinas Botulínicas , Botulismo , Clostridium botulinum , Bovinos , Animales , Cobayas , Botulismo/prevención & control , Botulismo/veterinaria , Hidróxido de Aluminio , Escherichia coli/genética , Vacunas Bacterianas/genética , Toxinas Botulínicas/genética , Clostridium botulinum/genética , Adyuvantes Inmunológicos , Anticuerpos Neutralizantes , Inmunidad , Anticuerpos Antibacterianos
17.
Environ Sci Pollut Res Int ; 31(11): 17339-17353, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38337119

RESUMEN

Petroleum spent hydroprocessing catalysts are hazardous solid waste, the efficient recycling of which is a serious challenge to refineries. However, information on the economic feasibility of spent catalysts recycling plants is scarce, which is critical for environmental authorities and decision-makers. In this work, an innovative recycling scheme targeting hydrometallurgical recovery of base metals (Ni, Mo, and V) and transforming low-value Al residue into a high-value boehmite (γ-AlOOH) as the key product was considered an efficient way to beneficiate the hazardous spent hydroprocessing catalysts. A preliminary techno-economic evaluation of such a recycling scheme was performed to assess the feasibility of the proposed recycling scheme. The recovery cost (valuable metals and boehmite) and potential revenue were estimated to study the economics of the process. The preliminary results have suggested that the recycling scheme is economically feasible with a high internal rate of return (IRR) of 12.3%, a net present value of 38.6 million USD, and a short payback period of 8.7 years. Furthermore, a sensitivity analysis (± 10%) conducted on key parameters showed that the selling prices of the finished products and the cost of chemicals were the most important factors affecting plant economics. Overall, the recycling scheme was sustainable and avoided landfilling of spent catalysts as the residue can be beneficiated into a high-value product. The results from the economic feasibility study are likely to assist the stakeholders and decision-makers in making investment and policy decisions for the valorization of spent hydroprocessing catalysts.


Asunto(s)
Hidróxido de Aluminio , Óxido de Aluminio , Petróleo , Estudios de Factibilidad , Metales , Reciclaje/métodos
18.
Expert Rev Vaccines ; 23(1): 283-293, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38369699

RESUMEN

INTRODUCTION: Inactivated vaccines were delivered to low- and middle-income countries during the early pandemics of COVID-19. Currently, more than 10 inactivated COVID-19 vaccines have been developed. Most inactivated vaccines contain an inactivated whole-cell index SARS-CoV-2 strain that is adjuvant. Whole virions inactivated with aluminum hydroxide vaccines were among the most commonly used. However, with the emerging of COVID-19 variants and waning of the immunity of two doses of after 3 months, WHO and many local governments have recommended the booster-dose program especially with heterologous platform vaccine. AREA COVERED: This review was conducted through a literature search of the MEDLINE database to identify articles published from 2020 to 2023 covered the inactivated COVID-19 vaccines primary series with homologous and heterologous booster focusing on safety, immunogenicity, efficacy, and effectiveness. EXPERT OPINION: The inactivated vaccines, especially whole virion inactivated in aluminum hydroxide appeared to be safe and had good priming effects. Immune responses generated after one dose of heterologous boost were high and able to preventing severity of disease and symptomatic infection. A new approach to inactivated vaccine has been developed using inactivating recombinant vector virus-NDV-HXP-S vaccine.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Humanos , Hidróxido de Aluminio , COVID-19/prevención & control , SARS-CoV-2 , Vacunas de Productos Inactivados/efectos adversos , Anticuerpos Antivirales , Inmunogenicidad Vacunal
19.
Water Environ Res ; 96(2): e10997, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38385894

RESUMEN

Polymeric membranes have garnered great interest in wastewater treatment; however, fouling is known as their main limitation. Therefore, the blending of hydrophilic nanoparticles in polymeric membranes' structure is a promising approach for fouling reduction. Herein, a hydrophilic boehmite-tannic acid-graphene quantum dot (BM-TA-GQD) nanoparticle was synthesized and blended in a polyethersulfone polymeric membrane in different percentages. The fabricated membranes were characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM) images, water contact angle, porosity measurement, and antibacterial and antifouling properties. Surface SEM images of the modified membranes showed good dispersion of nanoparticles up to 0.5 wt%, which resulted in hydrophilicity and pure water flux enhancement. Based on AFM images, the mean roughness (Sa) of the fabricated membranes decreased from 2.07 to 0.84 nm for the bare and optimum membranes, respectively. In terms of performance, increasing the nanoparticle percentages up to 0.5 wt% resulted in the flux recovery ratio developing from 44.58% for the bare membrane to 71.35% for the 0.5 wt% BM-TA-GQD/PES membrane (optimum membrane). The antibacterial property of fabricated membranes was studied against biologically treated soft drink industrial wastewater (BTSDIW) as a bacterial source. The results showed that the turbidity of solutions containing permeated wastewater from the modified membranes (0.1, 0.5, and 1 wt% of BM-TA-GQD) was lower than that obtained from the unmodified membrane. These results confirmed the antibacterial properties of fabricated membranes. Finally, the optimal membrane (0.5 wt% BM-TA-GQD) was examined for post-treatment of the BTSDIW. An effluent COD of 13 mg/L and turbidity of 2 NTU showed a successful performance of the filtration process. PRACTITIONER POINTS: Ultrafiltration PES membranes were modified by different loadings of BM-TA-GQD. Hydrophilicity improvement was achieved by adding BM-TA-GQD nanoparticles. Expansion of size and number of macro-voids in modified membranes was confirmed. Membrane roughness was reduced in the BM-TA-GQD blended membranes. The optimum membrane was efficient in COD and turbidity removal.


Asunto(s)
Hidróxido de Aluminio , Óxido de Aluminio , Grafito , Polímeros , Polifenoles , Puntos Cuánticos , Sulfonas , Aguas Residuales , Antibacterianos/farmacología , Bebidas Gaseosas , Agua
20.
J Clin Invest ; 134(7)2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38290009

RESUMEN

BACKGROUNDMalaria transmission-blocking vaccines aim to interrupt the transmission of malaria from one person to another.METHODSThe candidates R0.6C and ProC6C share the 6C domain of the Plasmodium falciparum sexual-stage antigen Pfs48/45. R0.6C utilizes the glutamate-rich protein (GLURP) as a carrier, and ProC6C includes a second domain (Pfs230-Pro) and a short 36-amino acid circumsporozoite protein (CSP) sequence. Healthy adults (n = 125) from a malaria-endemic area of Burkina Faso were immunized with 3 intramuscular injections, 4 weeks apart, of 30 µg or 100 µg R0.6C or ProC6C each adsorbed to Alhydrogel (AlOH) adjuvant alone or in combination with Matrix-M (15 µg or 50 µg, respectively). The allocation was random and double-blind for this phase I trial.RESULTSThe vaccines were safe and well tolerated with no vaccine-related serious adverse events. A total of 7 adverse events, mild to moderate in intensity and considered possibly related to the study vaccines, were recorded. Vaccine-specific antibodies were highest in volunteers immunized with 100 µg ProC6C-AlOH with Matrix-M, and 13 of 20 (65%) individuals in the group showed greater than 80% transmission-reducing activity (TRA) when evaluated in the standard membrane feeding assay at 15 mg/mL IgG. In contrast, R0.6C induced sporadic TRA.CONCLUSIONAll formulations were safe and well tolerated in a malaria-endemic area of Africa in healthy adults. The ProC6C-AlOH/Matrix-M vaccine elicited the highest levels of functional antibodies, meriting further investigation.TRIAL REGISTRATIONPan-African Clinical Trials Registry (https://pactr.samrc.ac.za) PACTR202201848463189.FUNDINGThe study was funded by the European and Developing Countries Clinical Trials Partnership (grant RIA2018SV-2311).


Asunto(s)
Vacunas contra la Malaria , Malaria Falciparum , Malaria , Adulto , Humanos , Plasmodium falciparum , Proteínas Protozoarias , Adyuvantes Inmunológicos , Antígenos de Protozoos , Hidróxido de Aluminio , Anticuerpos Antiprotozoarios
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