Immune Responses and Protective Immunity in Pangasius Pangasius (Hamilton, 1822) as Induced by Outer Membrane Proteins of Edwardsiella Tarda and Aluminium Hydroxide Adjuvant Complex

Edwardsiella tarda is considered one of the important bacterial fish pathogens. The outer membrane proteins (OMPs) of E. tarda are structurally and functionally conserved, and immunogenic. This study assessed the effects of the OMPs of E. tarda CGH9 as a vaccine without aluminium hydroxide [AH] (T1) and with AH adjuvant (T2) on the respiratory burst (ROB) activity, lymphocyte proliferation of head kidney (HK) leukocytes, and serum antibody production in pangas catfish Pangasius pangasius. The ROB activity and lymphocyte proliferation of HK leukocytes increased in both vaccinated groups compared to control. Nonetheless, the T2 group showed a gradual increase in ROB activity and lymphocyte proliferation of HK leukocytes up to 3-weeks post-vaccination (wpv). The serum antibody production in the T1 group decreased initially for up to 2-wpv and increased from 3-wpv; whereas, in the T2 group, the serum-specific antibody levels were significantly high from 1-wpv compared to control. Simultaneously, the protective efficacy in terms of relative percentage survival (RPS) in the T2 group after injecting with a lethal dose of E. tarda CGH9 was high (89.00±15.56) compared to the T1 group (78.00±0.00). Furthermore, the catfish administered with a booster dose of E. tarda OMPs with or without AH adjuvant showed no additional increase in immune response or protective immunity. These results suggested that E. tarda OMPs and AH adjuvant complex has a higher potential to induce protective immunity, which may be a good choice as a vaccine to combat E. tarda infection in catfish.

Characterization of Medication Trends for Chronic Kidney Disease: Mineral and Bone Disorder Treatment Using Electronic Health Record-Based Common Data Model

Chronic kidney disease–mineral bone disorder (CKD-MBD) is the most common complication in CKD patients. Although there is a consensus on treatment guidelines for CKD-MBD, it remains uncertain whether these treatment recommendations reflect actual practice. Therefore, the aim of this study was to investigate the CKD-MBD medication trend in real-world practice. This was a retrospective and observational study using a 12-year period database transformed into a common data model from three tertiary university hospitals. Study populations were subjects initially diagnosed as CKD. The date of diagnosis was designated as the index date. New patients were categorized year to year from 2008 to 2019 with a fixed observation period of 365 days to check the prescription of CKD-MBD medications including calcium-containing phosphate binder, noncalcium-containing phosphate binder, aluminium hydroxide, vitamin D receptor activator (VDRA), and cinacalcet. The numbers of CKD patients in the three hospitals were 7555, 2424, and 5351, respectively. The proportion for patients with CKD-MBD medication prescription decreased yearly regardless of hospital and CKD stage ( p for trend < 0.05). The use of aluminium hydroxide disappeared steadily while the use of VDRA increased annually in all settings. Despite these changes in prescription patterns, the mean value for CKD-MBD-related serologic markers was almost within target range. The proportion of the population within the target value was not significantly changed. Irrespective of hospital and CKD stage, similar trends of prescription for CKD-MBD medications were observed in real-world practice. Further research with a distributed network study may be helpful to understand medication trends in CKD-MBD treatment.

Synthesis and Thermal Treatment of Lithium- and Magnesium-Containing Geopolymers

<p>Geopolymers are a class of cementitious aluminosilicate materials that are receiving an increasing amount of attention due to their potential applications in toxic waste remediation and as construction materials. They are composed of a network of crosslinked silicate and aluminate tetrahedra with charge-balancing alkali cations and are therefore similar in composition to alkali aluminosilicate zeolites. They are, however, x-ray amorphous.¹⁻⁴ They are formed by the dissolution of a solid aluminosilicate in a solution of alkali hydroxide or alkali silicate to form aluminosilicate ions which subsequently polymerise. The effects of adding magnesium to metakaolin geopolymer systems was examined. Magnesium was added as soluble magnesium salts and as magnesium oxide and hydroxide. When added as a soluble salt, an amorphous magnesium (alumino)silicate with a lower degree of silicate polymerisation than a geopolymer is formed. When added as the oxide or hydroxide, hydrotalcite is formed. In both cases, the product is produced alongside a separate geopolymer phase. A magnesiumcontaining geopolymer phase was not found in either. When heated to 1200°C, geopolymers with magnesium oxide added bloated to form lightweight foams. Lithium analogues of conventional metakaolin geopolymer systems with a range of lithium, aluminium, silicon and water contents were examined. Systems with molar ratios similar to those of commonly studied sodium and potassium metakaolin geopolymers produce self-pelletised lithium zeolites. The zeolite formed was Li-EDI, the lithium analogue of zeolite F. This is the first reported synthesis directly from metakaolin. True lithium geopolymers are found not to form in the systems examined. The zeolite bodies react to form β-eucryptite and β-spodumene at temperatures from 800 – 1350°C. The use of aluminium hydroxide and amorphoud silica rather than aluminosilicates as raw materials for the formation of potassium geopolymers was found to produce geopolymers with embedded grains of unreacted silica and aluminium hydroxide.</p>

Synthesis and Thermal Treatment of Lithium- and Magnesium-Containing Geopolymers

<p>Geopolymers are a class of cementitious aluminosilicate materials that are receiving an increasing amount of attention due to their potential applications in toxic waste remediation and as construction materials. They are composed of a network of crosslinked silicate and aluminate tetrahedra with charge-balancing alkali cations and are therefore similar in composition to alkali aluminosilicate zeolites. They are, however, x-ray amorphous.¹⁻⁴ They are formed by the dissolution of a solid aluminosilicate in a solution of alkali hydroxide or alkali silicate to form aluminosilicate ions which subsequently polymerise. The effects of adding magnesium to metakaolin geopolymer systems was examined. Magnesium was added as soluble magnesium salts and as magnesium oxide and hydroxide. When added as a soluble salt, an amorphous magnesium (alumino)silicate with a lower degree of silicate polymerisation than a geopolymer is formed. When added as the oxide or hydroxide, hydrotalcite is formed. In both cases, the product is produced alongside a separate geopolymer phase. A magnesiumcontaining geopolymer phase was not found in either. When heated to 1200°C, geopolymers with magnesium oxide added bloated to form lightweight foams. Lithium analogues of conventional metakaolin geopolymer systems with a range of lithium, aluminium, silicon and water contents were examined. Systems with molar ratios similar to those of commonly studied sodium and potassium metakaolin geopolymers produce self-pelletised lithium zeolites. The zeolite formed was Li-EDI, the lithium analogue of zeolite F. This is the first reported synthesis directly from metakaolin. True lithium geopolymers are found not to form in the systems examined. The zeolite bodies react to form β-eucryptite and β-spodumene at temperatures from 800 – 1350°C. The use of aluminium hydroxide and amorphoud silica rather than aluminosilicates as raw materials for the formation of potassium geopolymers was found to produce geopolymers with embedded grains of unreacted silica and aluminium hydroxide.</p>

Mixed-Phase Ion-Exchangers from Waste Amber Container Glass

This study investigated the one-pot hydrothermal synthesis of mixed-phase ion-exchangers from waste amber container glass and three different aluminium sources (Si/Al = 2) in 4.5 M NaOH(aq) at 100 °C. Reaction products were characterised by X-ray diffraction analysis, Fourier transform infrared spectroscopy, 27Al and 29Si magic angle spinning nuclear magnetic resonance spectroscopy and scanning electron microscopy at 24, 48 and 150 h. Nitrated forms of cancrinite and sodalite were the predominant products obtained with reagent grade aluminium nitrate (Al(NO3)3∙9H2O). Waste aluminium foil gave rise to sodalite, tobermorite and zeolite Na-P1 as major phases; and the principal products arising from amorphous aluminium hydroxide waste were sodalite, tobermorite and zeolite A. Minor proportions of the hydrogarnet, katoite, and calcite were also present in each sample. In each case, crystallisation was incomplete and products of 52, 65 and 49% crystallinity were obtained at 150 h for the samples prepared with aluminium nitrate (AN-150), aluminium foil (AF-150) and amorphous aluminium hydroxide waste (AH-150), respectively. Batch Pb2+-uptake (~100 mg g−1) was similar for all 150-h samples irrespective of the nature of the aluminium reagent and composition of the product. Batch Cd2+-uptakes of AF-150 (54 mg g−1) and AH-150 (48 mg g−1) were greater than that of AN-150 (36 mg g−1) indicating that the sodalite- and tobermorite-rich products exhibited a superior affinity for Cd2+ ions. The observed Pb2+- and Cd2+-uptake capacities of the mixed-product ion-exchangers compared favourably with those of other inorganic waste-derived sorbents reported in the literature.

Neutralising antibodies against the SARS-CoV-2 Delta variant induced by Alhydroxyquim-II-adjuvanted trimeric spike antigens

Global control of COVID-19 will require the deployment of vaccines capable of inducing long-term protective immunity against SARS-CoV-2 variants. In this report, we describe an adjuvanted subunit candidate vaccine that affords elevated, sustained and cross-variant SARS-CoV-2 neutralising antibodies (NAbs) in multiple animal models. Alhydroxiquim-II is a TLR7/8 small-molecule agonist chemisorbed on aluminium hydroxide. Vaccination with Alhydroxiquim-II combined with a stabilized, trimeric form of the SARS-CoV-2 spike protein (termed CoVac-II) resulted in high-titre NAbs in mice, with no decay in responses over an 8-month period. NAbs from sera of CoVac-II-immunized mice, horses and rabbits were broadly neutralising against SARS-CoV-2 variants. Boosting long-term CoVac-II-immunized mice with adjuvanted spike protein from the Beta variant markedly increased levels of NAb titres against multiple SARS-CoV-2 variants; notably high titres against the Delta variant were observed. These data strongly support the clinical assessment of Alhydroxiquim-II-adjuvanted spike proteins to protect against SARS-CoV-2 variants of concern.

Safety and Immunogenicity of CpG 1018 and Aluminium Hydroxide-Adjuvanted SARS-CoV-2 S-2P Protein Vaccine MVC-COV1901: A Large-Scale Double-Blinded, Randomised, Placebo-Controlled Phase 2 Trial

Background We have assessed the safety and immunogenicity of MVC-COV1901, a recombinant protein vaccine containing prefusion-stabilized spike protein S-2P adjuvanted with CpG 1018 and aluminium hydroxide against COVID-19. Methods This is a phase 2, prospective, double-blinded, placebo-controlled, and multi-centre study to evaluate the safety, tolerability, and immunogenicity of the SARS-CoV-2 vaccine candidate MVC-COV1901. The study comprised 3,844 participants of ≥ 20 years who were generally healthy or with stable pre-existing medical conditions. The study participants were randomly assigned in a 6:1 ratio to receive either MVC-COV1901 containing 15 mcg of S-2P protein or placebo containing saline. Participants received two doses of MVC-COV1901 or placebo, administered 28 days apart via intramuscular injection. The primary outcomes were to evaluate the safety, tolerability, and immunogenicity of MVC-COV1901 from Day 1 (the day of first vaccination) to Day 57 (28 days after the second dose). Immunogenicity of MVC-COV1901 was assessed through geometric mean titres (GMT) and seroconversion rates (SCR) of neutralising antibody and antigen-specific immunoglobulin. This clinical trial is registered at ClinicalTrials.gov: NCT04695652. Findings From the start of this phase 2 trial to the time of interim analysis, no vaccine-related Serious Adverse Events (SAEs) was recorded. The most common solicited adverse events across all study participants were pain at the injection site (64%), and malaise/fatigue (35%). Fever was rarely reported (<1%). For all participants in the MVC-COV1901 group, at 28 days after the second dose against wild type SARS-CoV-2 virus, the GMT was 662.3 (408 IU/mL), the GMT ratio was 163.2, and the seroconversion rate was 99.8%. Interpretation MVC-COV1901 shows good safety profiles and promising immunogenicity responses. The current data supports MVC-COV1901 to enter phase 3 efficacy trials, and could enable regulatory considerations for Emergency Use Authorisation (EUA). Funding Medigen Vaccine Biologics Corporation and Taiwan Centres for Disease Control.