Immunogenicity and safety of SARS-CoV-2 recombinant protein subunit vaccine (IndoVac) adjuvanted with alum and CpG 1018 in Indonesian adults: A phase 3, randomized, active-controlled, multicenter trial.

BACKGROUND: Bio Farma has developed a recombinant protein subunit vaccine (IndoVac) that is indicated for active immunization in population of all ages. This article reported the results of the phase 3 immunogenicity and safety study in Indonesian adults aged 18 years and above. METHODS: We conducted a randomized, active-controlled, multicenter, prospective intervention study to evaluate the immunogenicity and safety of IndoVac in adults aged 18 years and above. Participants who were SARS-CoV-2 vaccine-naïve received two doses of either IndoVac or control (Covovax) with 28 days interval between doses and were followed up until 12 months after complete vaccination. RESULTS: A total of 4050 participants were enrolled from June to August 2022 and received at least one dose of vaccine. The geometric mean ratio (GMR) of neutralizing antibody at 14 days after the second dose was 1.01 (95 % confidence interval (CI) 0.89-1.16), which met the WHO non-inferiority criteria for immunobridging (95 % CI lower bound > 0.67). The antibody levels were maintained through 12 months after the second dose. The incidence rate of adverse events (AEs) were 27.95 % in IndoVac group and 32.15 % in Covovax group with mostly mild intensity (27.70 %). The most reported solicited AEs were pain (14.69 %) followed by myalgia (7.48 %) and fatigue (6.77 %). Unsolicited AEs varied, with each of the incidence rate under 5 %. There were no serious AEs assessed as possibly, probably, or likely related to vaccine. CONCLUSIONS: IndoVac in adults showed favourable safety profile and elicited non-inferior immune response to Covovax. (ClinicalTrials.gov: NCT05433285, Indonesian Clinical Research Registry: INA-R5752S9).

Development and preclinical evaluation of equine-derived hyperimmune serum against SARS-CoV-2 infection in K-18 hACE2 transgenic (Tg) mice.

This study aimed to develop an equine-derived hyperimmune serum against SARS-CoV-2 and evaluate its efficacy as a potential immunotherapy tool for the treatment of known and potential variants of COVID-19 in preclinical trials. The novelty of this study is the whole virus and ALUM gel adjuvant formula. The horses were immunized using a whole inactivated SARS-CoV-2 antigen, and the final purified hyperimmune serum showed high plaque reduction neutralization (PRNT 50) neutralizing titers. The efficacy of the hyperimmune serum was evaluated histopathologically and biochemically in the lungs, hearts, and serum of K18 hACE2 transgenic mice (n=45), which is an accepted model organism for SARS-CoV-2 studies and was challenged with live SARS-CoV-2. Serum treatment improved the general condition, resulting in lower levels of proinflammatory cytokines in the blood plasma, as well as reduced viral RNA titers in the lungs and hearts. Additionally, it reduced oxidative stress significantly and lessened the severity of interstitial pneumonia in the lungs when compared to infected positive controls. The study concluded that equine-derived anti-SARS-CoV-2 antibodies could be used for COVID-19 prevention and treatment, especially in the early stages of the disease and in combination with antiviral drugs and vaccines. This treatment will benefit special patient populations such as immunocompromised individuals, as specific antibodies against SARS-CoV-2 can neutralize the virus before it enters host cells. The rapid and cost-effective production of the serum allows for its availability during the acute phase of the disease, making it a critical intervention in preventing the spread of the disease and saving lives in new variants where a vaccine is not yet developed.

Alum/CpG adjuvant promotes immunogenicity of inactivated SARS-CoV-2 Omicron vaccine through enhanced humoral and cellular immunity.

The SARS-CoV-2 Omicron variant, which was classified as a variant of concern (VOC) by the World Health Organization on 26 November 2021, has attracted worldwide attention for its high transmissibility and immune evasion ability. The existing COVID-19 vaccine has been shown to be less effective in preventing Omicron variant infection and symptomatic infection, which brings new challenges to vaccine development and application. Here, we evaluated the immunogenicity and safety of an Omicron variant COVID-19 inactivated vaccine containing aluminum and CpG adjuvants in a variety of animal models. The results showed that the vaccine candidate could induce high levels of neutralizing antibodies against the Omicron variant virus and binding antibodies, and significantly promoted cellular immune response. Meanwhile, the vaccine candidate was safe. Therefore, it provided more foundation for the development of aluminum and CpG as a combination adjuvant in human 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.

An inactivated whole-virion vaccine for Enterovirus D68 adjuvanted with CpG ODN or AddaVax elicits potent protective immunity in mice.

Enterovirus D68 (EV-D68), a pathogen that causes respiratory symptoms, mainly in children, has been implicated in acute flaccid myelitis, which is a poliomyelitis-like paralysis. Currently, there are no licensed vaccines or treatments for EV-D68 infections. Here, we investigated the optimal viral inactivation reagents, vaccine adjuvants, and route of vaccination in mice to optimize an inactivated whole-virion (WV) vaccine against EV-D68. We used formalin, ß-propiolactone (BPL), and hydrogen peroxide as viral inactivation reagents and compared their effects on antibody responses. Use of any of these three viral inactivation reagents effectively induced neutralizing antibodies. Moreover, the antibody response induced by the BPL-inactivated WV vaccine was enhanced when adjuvanted with cytosine phosphoguanine oligodeoxynucleotide (CpG ODN) or AddaVax (MF59-like adjuvant), but not with aluminum hydroxide (alum). Consistent with the antibody response results, the protective effect of the inactivated WV vaccine against the EV-D68 challenge was enhanced when adjuvanted with CpG ODN or AddaVax, but not with alum. Further, while the intranasal inactivated WV vaccine induced EV-D68-specific IgA antibodies in the respiratory tract, it was less protective against EV-D68 challenge than the injectable vaccine. Thus, an injectable inactivated EV-D68 WV vaccine prepared with appropriate viral inactivation reagents and an optimal adjuvant is a promising EV-D68 vaccine.

Safety and immunogenicity of a subtype C ALVAC-HIV (vCP2438) vaccine prime plus bivalent subtype C gp120 vaccine boost adjuvanted with MF59 or alum in healthy adults without HIV (HVTN 107): A phase 1/2a randomized trial.

BACKGROUND: Adjuvants are widely used to enhance and/or direct vaccine-induced immune responses yet rarely evaluated head-to-head. Our trial directly compared immune responses elicited by MF59 versus alum adjuvants in the RV144-like HIV vaccine regimen modified for the Southern African region. The RV144 trial of a recombinant canarypox vaccine vector expressing HIV env subtype B (ALVAC-HIV) prime followed by ALVAC-HIV plus a bivalent gp120 protein vaccine boost adjuvanted with alum is the only trial to have shown modest HIV vaccine efficacy. Data generated after RV144 suggested that use of MF59 adjuvant might allow lower protein doses to be used while maintaining robust immune responses. We evaluated safety and immunogenicity of an HIV recombinant canarypox vaccine vector expressing HIV env subtype C (ALVAC-HIV) prime followed by ALVAC-HIV plus a bivalent gp120 protein vaccine boost (gp120) adjuvanted with alum (ALVAC-HIV+gp120/alum) or MF59 (ALVAC-HIV+gp120/MF59) or unadjuvanted (ALVAC-HIV+gp120/no-adjuvant) and a regimen where ALVAC-HIV+gp120 adjuvanted with MF59 was used for the prime and boost (ALVAC-HIV+gp120/MF59 coadministration). METHODS AND FINDINGS: Between June 19, 2017 and June 14, 2018, 132 healthy adults without HIV in South Africa, Zimbabwe, and Mozambique were randomized to receive intramuscularly: (1) 2 priming doses of ALVAC-HIV (months 0 and 1) followed by 3 booster doses of ALVAC-HIV+gp120/MF59 (months 3, 6, and 12), n = 36; (2) 2 priming doses of ALVAC-HIV (months 0 and 1) followed by 3 booster doses of ALVAC-HIV+gp120/alum (months 3, 6, and 12), n = 36; (3) 4 doses of ALVAC-HIV+gp120/MF59 coadministered (months 0, 1, 6, and 12), n = 36; or (4) 2 priming doses of ALVAC-HIV (months 0 and 1) followed by 3 booster doses of ALVAC-HIV+gp120/no adjuvant (months 3, 6, and 12), n = 24. Primary outcomes were safety and occurrence and mean fluorescence intensity (MFI) of vaccine-induced gp120-specific IgG and IgA binding antibodies at month 6.5. All vaccinations were safe and well-tolerated; increased alanine aminotransferase was the most frequent related adverse event, occurring in 2 (1.5%) participants (1 severe, 1 mild). At month 6.5, vaccine-specific gp120 IgG binding antibodies were detected in 100% of vaccinees for all 4 vaccine groups. No significant differences were seen in the occurrence and net MFI of vaccine-specific IgA responses between the ALVAC-HIV+gp120/MF59-prime-boost and ALVAC-HIV+gp120/alum-prime-boost groups or between the ALVAC-HIV+gp120/MF59-prime-boost and ALVAC-HIV+gp120/MF59 coadministration groups. Limitations were the relatively small sample size per group and lack of evaluation of higher gp120 doses. CONCLUSIONS: Although MF59 was expected to enhance immune responses, alum induced similar responses to MF59, suggesting that the choice between these adjuvants may not be critical for the ALVAC+gp120 regimen. TRIAL REGISTRATION: HVTN 107 was registered with the South African National Clinical Trials Registry (DOH-27-0715-4894) and ClinicalTrials.gov (NCT03284710).

Adjuvant screening of the Senecavirus A inactivated vaccine in mice and evaluation of its immunogenicity in pigs.

BACKGROUND: Senecavirus A (SVA) causes an emerging vesicular disease (VD) with clinical symptoms indistinguishable from other vesicular diseases, including vesicular stomatitis (VS), foot-and-mouth disease (FMD), and swine vesicular disease (SVD). Currently, SVA outbreaks have been reported in Canada, the U.S.A, Brazil, Thailand, Vietnam, Colombia, and China. Based on the experience of prevention and control of FMDV, vaccines are the best means to prevent SVA transmission. RESULTS: After preparing an SVA inactivated vaccine (CH-GX-01-2019), we evaluated the immunogenicity of the SVA inactivated vaccine mixed with Imject® Alum (SVA + AL) or Montanide ISA 201 (SVA + 201) adjuvant in mice, as well as the immunogenicity of the SVA inactivated vaccine combined with Montanide ISA 201 adjuvant in post-weaned pigs. The results of the mouse experiment showed that the immune effects in the SVA + 201 group were superior to that in the SVA + AL group. Results from pigs immunized with SVA inactivated vaccine combined with Montanide ISA 201 showed that the immune effects were largely consistent between the SVA-H group (200 µg) and SVA-L group (50 µg); the viral load in tissues and blood was significantly reduced and no clinical symptoms occurred in the vaccinated pigs. CONCLUSIONS: Montanide ISA 201 is a better adjuvant choice than the Imject® Alum adjuvant in the SVA inactivated vaccine preparation, and the CH-GX-01-2019 SVA inactivated vaccine can provide effective protection for pigs.

Immunogenicity and safety in rabbits of a Clostridioides difficile vaccine combining novel toxoids and a novel adjuvant.

Clostridioides difficile infection (CDI) is a serious healthcare-associated disease, causing symptoms such as diarrhea and pseudomembranous colitis. The major virulence factors responsible for the disease symptoms are two secreted cytotoxic proteins, TcdA and TcdB. A parenteral vaccine based on formaldehyde-inactivated TcdA and TcdB supplemented with alum adjuvant, has previously been investigated in humans but resulted in an insufficient immune response. In search for an improved response, we investigated a novel toxin inactivation method and a novel, potent adjuvant. Inactivation of toxins by metal-catalyzed oxidation (MCO) was previously shown to preserve neutralizing epitopes and to annihilate reversion to toxicity. The immunogenicity and safety of TcdA and TcdB inactivated by MCO and combined with a novel carbohydrate fatty acid monosulphate ester-based (CMS) adjuvant were investigated in rabbits. Two or three intramuscular immunizations generated high serum IgG and neutralizing antibody titers against both toxins. The CMS adjuvant increased antibody responses to both toxins while an alum adjuvant control was effective only against TcdA. Systemic safety was evaluated by monitoring body weight, body temperature, and analysis of red and white blood cell counts shortly after immunization. Local safety was assessed by histopathologic examination of the injection site at the end of the study. Body weight gain was constant in all groups. Body temperature increased up to 1 ˚C one day after the first immunization but less after the second or third immunization. White blood cell counts, and percentage of neutrophils increased one day after immunization with CMS-adjuvanted vaccines, but not with alum. Histopathology of the injection sites 42 days after the last injection did not reveal any abnormal tissue reactions. From this study, we conclude that TcdA and TcdB inactivated by MCO and combined with CMS adjuvant demonstrated promising immunogenicity and safety in rabbits and could be a candidate for a vaccine against CDI.

Enhanced immunogenicity and protective efficacy in mice following a Zika DNA vaccine designed by modulation of membrane-anchoring regions and its association to adjuvants.

Zika virus (ZIKV) is a re-emerging pathogen with high morbidity associated to congenital infection. Despite the scientific advances since the last outbreak in the Americas, there are no approved specific treatment or vaccines. As the development of an effective prophylactic approach remains unaddressed, DNA vaccines surge as a powerful and attractive candidate due to the efficacy of sequence optimization in achieving strong immune response. In this study, we developed four DNA vaccine constructs encoding the ZIKV prM/M (pre-membrane/membrane) and E (envelope) proteins in conjunction with molecular adjuvants. The DNA vaccine candidate (called ZK_ΔSTP), where the entire membrane-anchoring regions were completely removed, was far more immunogenic compared to their counterparts. Furthermore, inclusion of the tPA-SP leader sequence led to high expression and secretion of the target vaccine antigens, therefore contributing to adequate B cell stimulation. The ZK_ΔSTP vaccine induced high cellular and humoral response in C57BL/6 adult mice, which included high neutralizing antibody titers and the generation of germinal center B cells. Administration of ZK-ΔSTP incorporating aluminum hydroxide (Alum) adjuvant led to sustained neutralizing response. In consistency with the high and long-term protective response, ZK_ΔSTP+Alum protected adult mice upon viral challenge. Collectively, the ZK_ΔSTP+Alum vaccine formulation advances the understanding of the requirements for a successful and protective vaccine against flaviviruses and is worthy of further translational studies.

Efficacy of adjuvant-associated COVID-19 vaccines against SARS-CoV-2 variants of concern in randomized controlled trials: A systematic review and meta-analysis.

BACKGROUND: Adjuvants may enhance the efficacy of vaccines. however, the efficacy of adjuvant-associated COVID-19 vaccines (ACVs) remains unclear since the emergence of the COVID-19 pandemic. This study aimed to address this gap by conducting a systematic review and meta-analysis of the efficacy of ACVs against Severe Acute Respiratory Syndrome Coronavirus 2 CoV (SARS-CoV-2) variants of concern (VOC). METHODS: A systematic search was conducted of randomized controlled trials (RCTs) evaluating the vaccine efficacy (VE) of ACVs against VOC (alpha, beta, gamma, delta, or Omicron), up to May 27, 2023. The DerSimonian-Laird random-effects model was used to assess VE with 95% confidence intervals (CI) through meta-analysis. Cochrane Risk of Bias tools were used to assess the risk of bias in RCTs. RESULTS: Eight RCTs with 113,202 participants were included in the analysis, which incorporated 4 ACVs [Matrix-M (NVX-CoV2373), Alum (BBV152), CpG-1018/Alum (SCB-2019), and AS03 (CoVLP]). The pooled efficacy of full vaccination with ACVs against VOC was 88.0% (95% CI: 83.0-91.5). Full vaccination was effective against Alpha, Beta, Delta, and Gamma variants, with VE values of 93.66% (95% CI: 86.5-100.74), 64.70% (95% CI: 41.87-87.54), 75.95% (95% CI: 67.9-83.99), and 91.26% (95% CI: 84.35-98.17), respectively. Currently, there is a lack of RCT evidence regarding the efficacy of ACVs against the Omicron variant. CONCLUSION: In this meta-analysis, it should be that full vaccination with ACVs has high efficacy against Alpha or Gamma variants and moderate efficacy against Beta and Delta variants. Notably, with the exception of the aluminum-adjuvanted vaccine, the other ACVs had moderate to high efficacy against the SARS-CoV-2 variant. This raises concerns about the effectiveness of ACVs booster vaccinations against Omicron.

Use of wastewater alum-coagulation sludge as a phosphorus fertiliser - a mini review.

The use of aluminium (Al) salts, particularly alum, in coagulation is a widespread and conventional treatment method for eliminating pollutants, including phosphorus (P) which can cause eutrophication, from wastewater. However, a significant challenge of this process is the substantial amount of sludge generated, necessitating proper disposal. Historically, land disposal has been a common practice, but it poses potential issues for plant life on these lands. Despite the associated drawbacks, sludge contains elevated concentrations of vital plant nutrients like P and nitrogen, presenting an opportunity for beneficial use in agriculture. Given the imminent scarcity of P fertilizers due to the eventual depletion of high-grade P ores, this review explores the potential advantages and challenges of utilizing Al sludge as a P source for plants and proposes measures for its beneficial application. One primary concern with land application of Al sludge is its high levels of soluble Al, known to be toxic to plants, particularly in acidic soils. Another issue arises from the elevated Al concentration is P fixation and subsequently reducing P uptake by plants. To address these issues, soil treatment options such as lime, gypsum, and organic matter can be employed. Additionally, modifying the coagulation process by substituting part of the Al salts with cationic organic polymers proves effective in reducing the Al content of the sludge. The gradual release of P from sludge into the soil over time proves beneficial for plants with extended growth periods.

Machine learning facilitated the conceptual design of an alum dosing system for phosphorus removal in a wastewater treatment plant.

Wastewater treatment plants (WWTPs) face challenges in controlling total phosphorus (TP), given more stringent regulations on TP discharging. In particular, WWTPs that operate at a small scale lack resources for real-time monitoring of effluent quality. This study aimed to develop a conceptual alum dosing system for reducing TP concentration, leveraging machine learning (ML) techniques and data from a full-scale WWTP containing incomplete TP information. The proposed system comprises two ML models in series: an Alert model based on LightGBM with an accuracy of 0.92, and a Dosage model employing a voting algorithm through combining three ML algorithms (LightGBM, SGD, and SVC) with an accuracy of 0.76. The proposed system has demonstrated the potential to ensure that 88.1% of the effluent remains below the TP discharge limit, which outperforms traditional dosing methods and could reduce overdosing from 61.3 to 12.1%. Furthermore, the SHapley Additive exPlanations (SHAP) analysis revealed that incorporating the output features from the previous cycle and utilizing the results of the Alert model as the input features for dosage prediction could be an effective method for data with limited information. The findings of this study have practical applications in improving the efficiency and effectiveness of TP control in small-scale WWTPs, providing a valuable solution for complying with stringent regulations and enhancing environmental sustainability.

Virus-like particle vaccine displaying an external, membrane adjacent MUC16 epitope elicits ovarian cancer-reactive antibodies.

BACKGROUND: MUC16 is a heavily glycosylated cell surface mucin cleaved in the tumor microenvironment to shed CA125. CA125 is a serum biomarker expressed by > 95% of non-mucinous advanced stage epithelial ovarian cancers. MUC16/CA125 contributes to the evasion of anti-tumor immunity, peritoneal spread and promotes carcinogenesis; consequently, it has been targeted with antibody-based passive and active immunotherapy. However, vaccination against this self-antigen likely requires breaking B cell tolerance and may trigger autoimmune disease. Display of self-antigens on virus-like particles (VLPs), including those produced with human papillomavirus (HPV) L1, can efficiently break B cell tolerance. RESULTS: A 20 aa juxta-membrane peptide of the murine MUC16 (mMUC16) or human MUC16 (hMUC16) ectodomain was displayed either via genetic insertion into an immunodominant loop of HPV16 L1-VLPs between residues 136/137, or by chemical coupling using malemide to cysteine sulfhydryl groups on their surface. Female mice were vaccinated intramuscularly three times with either DNA expressing L1-MUC16 fusions via electroporation, or with alum-formulated VLP chemically-coupled to MUC16 peptides. Both regimens were well tolerated, and elicited MUC16-specific serum IgG, although titers were higher in mice vaccinated with MUC16-coupled VLP on alum as compared to L1-MUC16 DNA vaccination. Antibody responses to mMUC16-targeted vaccination cross-reacted with hMUC16 peptide, and vice versa; both were reactive with the surface of CA125+ OVCAR3 cells, but not SKOV3 that lack detectable CA125 expression. Interestingly, vaccination of mice with mMUC16 peptide mixed with VLP and alum elicited mMUC16-specific IgG, implying VLPs provide robust T help and that coupling may not be required to break tolerance to this epitope. CONCLUSION: Vaccination with VLP displaying the 20 aa juxta-membrane MUC16 ectodomain, which includes the membrane proximal cleavage site, is likely to be well tolerated and induce IgG targeting ovarian cancer cells, even after CA125 is shed.

An Immunomodulatory Zinc-Alum/Ovalbumin Nanovaccine Boosts Cancer Metalloimmunotherapy Through Erythrocyte-Assisted Cascade Immune Activation.

Cancer therapeutic vaccines are powerful tools for immune system activation and eliciting protective responses against tumors. However, their efficacy has often been hindered by weak and slow immune responses. Here, the authors introduce an immunization strategy employing senescent erythrocytes to facilitate the accumulation of immunomodulatory zinc-Alum/ovalbumin (ZAlum/OVA) nanovaccines within both the spleen and solid tumors by temporarily saturating liver macrophages. This approach sets the stage for boosted cancer metalloimmunotherapy through a cascade immune activation. The accumulation of ZAlum/OVA nanovaccines in the spleen substantially enhances autophagy-dependent antigen presentation in dendritic cells, rapidly initiating OVA-specific T-cell responses against solid tumors. Concurrently, ZAlum/OVA nanovaccines accumulated in the tumor microenvironment trigger immunogenic cell death, leading to the induction of individualized tumor-associated antigen-specific T cell responses and increased T cell infiltration. This erythrocyte-assisted cascade immune activation using ZAlum/OVA nanovaccines results in rapid and robust antitumor immunity induction, holding great potential for clinical cancer metalloimmunotherapy.

Ammonia and greenhouse gas emissions from beef feedlot surface material treated with aluminum sulfate (alum) or microbial amendments.

A lab-scale study evaluated ammonia (NH3 ) and greenhouse gases, emissions when aluminum sulfate (alum) or a microbial product were added to beef feedlot surface material (FSM). Three kilograms of FSM and 1.5 kg of water were added to stainless steel pans (50 cm × 30 cm × 6.5 cm). Treatments included a control (no amendment), 450 g alum, or 0.5 g microbial product. The pans were placed in an environmental chamber that was maintained at 23°C and 50%-60% humidity. Emissions were measured three times weekly for 3 weeks. Ammonia, N2 O, and CH4 were lower (p < 0.01) from pans with amendments compared to the control pans; emissions from the FSM that received the microbial treatment were lower than the FSM treated with alum. Methane emissions were similar for the control and alum-treated FSM but lower (p < 0.01) for the FSM that was treated with the microbial product. Nitrate-N was lower, and NH4+ -N and total sulfur concentrations were higher in FSM treated with alum compared to no treatment or the microbial treatment (p < 0.01). Results indicate that both alum and microbial amendments have benefits in reducing emissions from the feedlot surface, with the microbial product providing additional reductions in emissions compared to the alum.

Stainability and translucency of potassium aluminum sulfate applied computer-aided design and computer-aided manufacturing materials after coffee thermocycling.

OBJECTIVE: The purpose of this in vitro study was to evaluate the effect of potassium aluminum sulfate (alum) application on the stainability and translucency of computer-aided design and computer-aided manufacturing (CAD-CAM) materials after coffee thermocycling (CTC). MATERIALS AND METHODS: Disk-shaped specimens (Ø10 × 1 mm; N = 200) were fabricated by using additively (Crowntec [CT] and Varseo Smile Crown Plus [VS]) and subtractively manufactured (Brilliant Crios [RCR], CEREC Block [FC], and Vita Enamic [VE]) CAD-CAM materials and polished. All specimens were randomly divided into two groups as alum applied and control (n = 10). All specimens were then subjected to CTC (10,000 cycles at 5-55°C) and color coordinates were measured at each time interval. Color differences (ΔE00 ) and relative translucency parameters (RTPs) were calculated and the data were statistically analyzed (a = 0.05). RESULTS: Among tested time intervals, alum applied specimens had their lowest ΔE00 after alum application (p ≤ 0.006), except for FC (p = 0.177). In addition, alum applied RCR had lower ΔE00 values than its control specimens (p = 0.029). Alum applied specimens had their lowest RTP after CTC (p < 0.001) and alum application decreased the RTP of CT (p = 0.010). CTC reduced the RTP of all materials in control groups (p < 0.001). Alum applied CT had higher RTP than its control specimens (p = 0.049). CONCLUSIONS: Alum application's effect on color change varied depending on the material and alum mostly resulted in clinically acceptable changes in translucency. CTC led to unacceptable color and translucency changes based on previously reported threshold values. CLINICAL SIGNIFICANCE: Optical properties of CAD-CAM materials and the sustainability of these properties over time is critical for longevity. Alum may improve the color stability of reinforced composite resin when subjected to long-term coffee consumption.

Optimization of syngas production from co-gasification of palm oil decanter cake and alum sludge: An RSM approach with char characterization.

The study explores co-gasification of palm oil decanter cake and alum sludge, investigating the correlation between input variables and syngas production. Operating variables, including temperature (700-900 °C), air flow rate (10-30 mL/min), and particle size (0.25-2 mm), were optimized to maximize syngas production using air as the gasification agent in a fixed bed horizontal tube furnace reactor. Response Surface Methodology with the Box-Behnken design was used employed for optimization. Fourier Transformed Infra-Red (FTIR) and Field Emission Scanning Electron Microscopic (FESEM) analyses were used to analyze the char residue. The results showed that temperature and particle size have positive effects, while air flow rate has a negative effect on the syngas yield. The optimal CO + H2 composition of 39.48 vol% was achieved at 900 °C, 10 mL/min air flow rate, and 2 mm particle size. FTIR analysis confirmed the absence of C─Cl bonds and the emergence of Si─O bonds in the optimized char residue, distinguishing it from the raw sample. FESEM analysis revealed a rich porous structure in the optimized char residue, with the presence of calcium carbonate (CaCO3) and aluminosilicates. These findings provide valuable insights for sustainable energy production from biomass wastes.

An enveloped virus-like particle alum-adjuvanted cytomegalovirus vaccine is safe and immunogenic: A first-in-humans Canadian Immunization Research Network (CIRN) study.

INTRODUCTION: Cytomegalovirus (CMV) is the most common cause of congenital infection and affected children often have permanent neurodevelopmental sequelae, including hearing loss and intellectual disability. Vaccines to prevent transmission of CMV during pregnancy are a public health priority. This first-in-humans dose-ranging, randomized, placebo-controlled, observer-blinded study evaluated the safety and immunogenicity of an enveloped virus-like particle (eVLP) vaccine expressing a modified form of the CMV glycoprotein B (gB). METHODS: Healthy CMV-seronegative 18 to 40-year-olds at 3 Canadian study sites were randomized to one of 4 dose formulations (0.5 µg, 1 µg, or 2 µg gB content with alum) or 1 µg gB without alum, or placebo, given intramuscularly on days 0, 56 and 168. Outcome measures were solicited and unsolicited adverse events (AE), severe AE, gB and AD-2 epitope binding antibody titers and avidity, and neutralizing antibody (nAb) titers to CMV measured in fibroblast and epithelial cell infection assays. RESULTS: Among 125 participants, the most common solicited local and general AEs were pain and headache, respectively. A dose-dependent increase in gB binding, avidity and nAb titers was observed after doses 2 and 3, with the highest titers in the alum-adjuvanted 2.0 µg dose recipients after the third dose; in the latter 24 % had responses to the broadly neutralizing AD-2 epitope. Neutralizing activity to CMV infection of fibroblasts was seen in 100 % of 2.0 µg alum-adjuvanted dose recipients, and to epithelial cell infection in 31 %. Epithelial cell nAb titers were positively correlated with higher geometric mean CMV gB binding titers. CONCLUSIONS: An eVLP CMV vaccine was immunogenic in healthy CMV-seronegative adults and no safety signals were seen. Alum adjuvantation increased immunogenicity as did higher antigen content and a three dose schedule. This phase 1 trial supports further development of this eVLP CMV vaccine candidate.

Parametric study of coagulant recovery from water treatment sludge towards water circular economy.

This study aims to recover the used coagulants from two water treatment plants via acidification technique. The water treatment sludge (WTS) was acidified with sulfuric acid (H2SO-4) at variable normalities (0.5, 1, 1.5, 2.0 and 2.5 N). The surface morphology and functionalities of both recovered coagulants were analysed using scanning electron microscopy (SEM) and Fourier-transform infrared spectroscopy (FTIR). The performance of recovered coagulants was tested for turbidity removal in surface water treatment at different coagulant dosages and pH. It was found that the optimum normality of H2SO4 for recovered alum was 1.5 N, where 66% turbidity removal was recorded. The recovered PAC treated with 1.0 N H2SO4 indicated high turbidity removal percentage, which was 50.5%. The turbidity removal increased with increasing coagulant dosage. More than 80% turbidity removal was achieved with 40 mg/L dosage of recovered alum and recovered PAC. Maximum removal (85%) was observed with 50 mg/L dosage of recovered alum. For commercial coagulant, the turbidity removal was higher, with a difference of up to 6% in favor of recovered alum. The potential reuse of coagulants can be explored in order to reduce the operating costs and promotes the reduction of WTS disposal.

Evaluation of a New Mordant Based Haematoxylin Dye (Haematoxylin X) for Use in Clinical Pathology.

Recently, St John's Dermatopathology Laboratory and CellPath Ltd have developed a new patented haematoxylin dye (Haematoxylin X) that utilises a chromium-based mordant (Chromium Sulphate). In this study, the performance of this new haematoxylin (Haematoxylin X) was compared against some commonly utilised alum-based haematoxylins (Carazzi's, Harris' and Mayer's) when used as a part of formalin-fixed paraffin embedded (FFPE) tissue, special stains, immunohistochemical counterstaining and frozen section (Mohs procedure) staining procedures. FFPE sections of different tissue types and frozen skin tissues were sectioned and stained with each haematoxylin subtype to allow for a direct comparison of staining quality. The slides were independently evaluated microscopically by two assessors. A combined score was generated to determine the sensitivity (defined as the intensity of haematoxylin staining being too weak or too strong and the colour of the haematoxylin staining not being blue/black) and specificity (defined as the presence of haematoxylin background staining, uneven staining, and staining deposits) for each of the four haematoxylin subtypes. The scoring criteria were based on the UKNEQAS Cellular pathology techniques assessment criteria. In FFPE tissue, the results for specificity identified Harris haematoxylin scoring the highest (91.2%) followed by Haematoxylin X (88.0%) and Mayer's (87.0%). The sensitivity scores again identified Harris haematoxylin as scoring the highest (95.1%) followed by Haematoxylin X (90.0%) and Mayer's (88.0%). In frozen tissue, the results for specificity identified Haematoxylin X as scoring the highest (85.5%) followed by Carazzi's (80.7%) and Harris' (77.4%). The sensitivity scores again identified Haematoxylin X as scoring the highest (86.8%) followed by Carazzi's (82.0%) and Harris' (81.0%). The results achieved with all four haematoxylins showed a high degree of comparability, with Harris' haematoxylin scoring high scores overall compared to the other four when assessing FFPE sections. This may have been due to familiarity with the use of Harris' haematoxylin in-house. There was also evidence of more pronounced staining of extracellular mucin proteins with Haematoxylin X compared to the other alum haematoxylins that were assessed. Haematoxylin X scored highest when used in frozen section staining. In addition, Haematoxylin X has a potential applications for use in IHC and special stains procedures as a counterstain.