OBJECTIVE: The present study aimed to evaluate the immunogenicity of BA.2 variant receptor binding domain (RBD) recombinant protein formulated with CpG 1826 plus alum dual adjuvant. METHODS: The BA.2 variant RBD (residues 308-548) fusing TT-P ₂ epitope was obtained from prokaryotic expression system, purification technology and dialysis renaturation, which was designated as Sot protein. The soluble Sot protein formulated with CpG 1826 plus alum dual adjuvant was designated as Sot/CA subunit vaccine and then the BALB/c mice were intramuscularly administrated with two doses of the Sot/CA subunit vaccine at 14-day interval (day 0 and 14). On day 28, the number of effector T lymphocytes secreting IFN-γ and IL-4 in mice spleen were determined by enzyme-linked immunospot (ELISpot) assay. The serum IgG, IgG1 and IgG2a antibodies were examined by enzyme-linked immunosorbent assay (ELISA). In addition, the level of neutralizing antibodies (NAbs) induced by Sot/CA subunit vaccine was also evaluated by the microneutralization assay. RESULTS: The high-purity soluble Sot protein with antigenicity was successfully obtained by the prokaryotic expression, protein purification and dialysis renaturation. The Sot/CA subunit vaccine induced a high level of IgG antibodies and NAbs, which were of cross-neutralizing activity against SARS-CoV-2 BA.2 and XBB.1.5 variants. Meanwhile, Sot/CA subunit vaccine also induced a high level of effector T lymphocytes secreting IFN-γ (635.00 ± 17.62) and IL-4 (279.20 ± 13.10), respectively. Combined with a decreased IgG1/IgG2a ratio in the serum, which indicating Sot/CA subunit vaccine induced a Th1-type predominant immune response. CONCLUSION The Sot protein formulated with CpG 1826 plus alum dual adjuvant showed that the excellent cellular and humoral immunogenicity, which provided a scientific basis for the development of BA.2 variant subunit vaccines and references for the adjuvant application of subunit vaccines.
Animals ; COVID-19 Vaccines/immunology* ; Alum Compounds/pharmacology* ; Mice, Inbred BALB C ; Vaccines, Subunit/immunology* ; Mice ; SARS-CoV-2/immunology* ; Oligodeoxyribonucleotides/administration & dosage* ; Female ; Adjuvants, Immunologic ; COVID-19/immunology* ; Antibodies, Viral/blood* ; Immunogenicity, Vaccine ; Spike Glycoprotein, Coronavirus/immunology* ; Antibodies, Neutralizing/blood* ; Adjuvants, Vaccine ; Immunoglobulin G/blood*

OBJECTIVE: This study aimed to investigate the effects of Montanide ISA-720 and Naloxone (NLX) in Hepatitis B surface antigen (HBsAg) vaccine formulation on cytokine and long-lasting antibody responses. METHODS: First, the HBsAg was formulated in Montanide ISA-720 adjuvant and Naloxone at 5 and 10 mg/kg. The experimental mice were immunized three times at a 2-week interval, and then IL-4, IL-2, TNF-α, and IFN-γ cytokines; long-lasting IgG antibody responses 220 days after the last shot; and IgG1/IgG2a isotypes were assessed by ELISA. RESULTS: The HBsAg-Alum group exhibited the highest IL-4 cytokine response among the experimental groups, whereas NLX in HBsAg-MON720 vaccine formulation did not affect cytokine responses. In addition, NLX in Alum-based vaccine suppressed IL-4 cytokine response and increased the IL-2/IL-4 cytokine ratio. Moreover, HBsAg-MON720 was more potent than HBsAg-Alum in the induction of antibody responses, and NLX in Alum- and MON720-based vaccines induced long-lasting antibody responses. CONCLUSION NLX in Alum-based vaccine decreased IL-4 cytokine response, increased IL-2/IL-4 cytokine ratio, and improved long-lasting humoral immune responses in both vaccine formulations. Therefore, the adjuvant activity of NLX in the vaccine formulation depends on the type of adjuvant and the nature of the antigen in the vaccine formulation.
Adjuvants, Immunologic/pharmacology* ; Alum Compounds ; Animals ; Cytokines ; Hepatitis B Surface Antigens ; Hepatitis B Vaccines ; Immunity, Humoral ; Immunoglobulin G ; Interleukin-2 ; Interleukin-4 ; Mice ; Mice, Inbred BALB C ; Mineral Oil ; Naloxone/pharmacology* ; Tumor Necrosis Factor-alpha

OBJECTIVETo explore the pro-inflammatory toxicity of Pinellia pedatiecta, as well as the alum processing method on its pro-inflammatory effect.

METHODRaphide and agglutinin (PPA) proteins were isolated from fresh P. pedatiecta. The overall animal and cellular level models were applied to investigate the pro-inflammatory effect of raphide and PPA in P. pedatiecta, as well as the impact of the alum processing method on the pro-inflammatory effect, with inflammatory mediators as the index.

RESULTIntraperitoneal injection with P. pedatiecta raphide suspension could significantly increase the content of inflammatory mediators PGE2 and NO. After the alum processing method was adopted, fresh P. pedatiecta and raphide-induced PGE2 and NO release significantly reduced. The stimulation of mice macrophages with P. pedatiecta agglutinin protein could cause the content of dose-dependent inflammatory mediators TNF-alpha and IL-6. After the alum processing method was adopted, PGE2 content in P. pedatiecta agglutinin protein-induced mice peritoneal exudate notably decreased.

CONCLUSIONThe irritation and toxicity of P. pedatiecta were inflammatory responses in organisms. Its raphide and agglutinin proteins were toxic components, both could cause significant the release of inflammatory medium. The alum processing method could help significantly reduce the pro-inflammatory toxicity of P. pedatiecta.

Alum Compounds ; chemistry ; Animals ; Drug Compounding ; methods ; Drugs, Chinese Herbal ; chemistry ; toxicity ; Female ; Inflammation Mediators ; chemistry ; toxicity ; Interleukin-6 ; immunology ; Macrophages ; drug effects ; immunology ; Male ; Mice, Inbred ICR ; Pinellia ; adverse effects ; chemistry ; Tumor Necrosis Factor-alpha ; immunology

Aluminum hydroxide (alum) is the most widely used adjuvant in human vaccines. Nevertheless, it is virtually unknown whether alum acts on B cells. In the present study, we explored the direct effect of alum on Ig expression by murine B cells in vitro. LPS-activated mouse spleen B cells were cultured with alum, and the level of isotype-specific Ig secretion, IgG1 secreting cell numbers, and Ig germ-line transcripts (GLT) were measured using ELISA, ELISPOT, and RT-PCR, respectively. Alum consistently enhanced total IgG1 production, numbers of IgG1 secreting cells, and GLTgamma1 expression. These results demonstrate that alum can directly cause IgG1 isotype switching leading to IgG1 production.
Alum Compounds ; Aluminum Hydroxide ; Animals ; B-Lymphocytes ; Cell Count ; Enzyme-Linked Immunosorbent Assay ; Enzyme-Linked Immunospot Assay ; Humans ; Hydroxides ; Immunoglobulin Class Switching ; Immunoglobulin G ; Mice ; Spleen ; Vaccines

A quick hemostatic effect, as well as sclerosing and shrinkage of hemorrhoids, can be attained when internal hemorrhoids are treated by using injection therapy with aluminum potassium sulfate and tannic acid (ALTA), the outcomes of treatment may be similar to those of a hemorrhoidectomy. However, if the type of hemorrhoid or the method of injection is not appropriate for ALTA treatment, complications peculiar to ALTA or recurrence may develop. Accordingly, sufficient understanding of the treatment mechanism of ALTA injection and repeated training for injection are required for effective use of the ALTA treatment.
Alum Compounds ; Aluminum ; Hemorrhoidectomy ; Hemorrhoids ; Potassium ; Recurrence ; Tannins

Phagocytosis and innate immune responses to solid structures are topics of interest and debate. Alum, monosodium urate, calcium pyrophosphate dehydrate, silica and by extension all solid entities draw varying degrees of attention from phagocytes, such as antigen presenting cells. For some, innocuous soluble metabolites turn into fierce irritants upon crystallization, pointing to divergent signaling mechanisms of a given substance in its soluble and solid states. Over the years, many mechanisms have been proposed, including phagocytic receptors, toll like receptors, and NACHT-LRRs (NLRs), as well as several other protein structure mediated recognition of the solids. Is there a more general mechanism for sensing solids? In this perspective, I present an alternative view on the topic that membrane lipids can engage solid surfaces, and the binding intensity leads to cellular activation. I argue from the stands of evolution and biological necessity, as well as the progression of our understanding of cellular membranes and phagocytosis. The effort is to invite debate of the topic from a less familiar yet equally thrilling viewing angle.
Adjuvants, Immunologic ; Alum Compounds ; Animals ; Antigen-Presenting Cells ; cytology ; immunology ; Biological Evolution ; Calcium Pyrophosphate ; immunology ; Cell Membrane ; immunology ; Humans ; Immunity, Innate ; Membrane Lipids ; immunology ; Phagocytes ; cytology ; immunology ; Phagocytosis ; immunology ; Phase Transition ; Receptors, Pattern Recognition ; immunology ; Signal Transduction ; immunology ; Silicon Dioxide ; immunology ; Uric Acid ; immunology

OBJECTIVEElucidating the detoxification mechanism of the raw Pinellia ternata processed by alum solution or alkaline solution (pH > 12).

METHODRaw Pinellia ternata was immersed in alum solution and alkaline solution according to Chinese pharmacopoeia. Observed the shape's changing of needle-like calcium oxalate crystals by scanning electro-microscopy. Determinating the contents of calcium oxalate crystals by applying oxidation reduction titration. Measured the irritations of raw P. ternata and various processing products on the model of rabbits'eyes.

RESULTAfter processed by 8% alum solution prescribed in Chinese pharmacopoeia or 10% sodium carbonate solution, the needle-like shape of raphides in raw Pinellia ternata were changing and the sting barb of raphides were rusted and dissolved, the contents of calcium oxalate crystal in raw Pinellia ternata were sharply declined from more than 1% to less than 0.5%. the decline of contents is relative to the irritation decline of P. ternata on rabbit's eyes. Less than 0.5% calcium oxalate crystals of P. ternata almost had no irritation.

CONCLUSIONAfter processed by 8% alum solution or sodium carbonate solution (pH > 12) , the irritation components in raw P. ternata could be rusted and dissolved, the needle point of raphides was broken, which led to the raphides'content declining and the irritation disappearing. The micro-structures, shapes and contents of calcium oxalate crystals in different medicine plants were not same. These properties of calcium oxalate crystal in India Madder Root and yam et al were very different from those in raw P. ternata.

Alum Compounds ; chemistry ; Animals ; Calcium Oxalate ; analysis ; isolation & purification ; toxicity ; Carbonates ; chemistry ; Conjunctiva ; drug effects ; Crystallization ; Drug Interactions ; Eye Diseases ; chemically induced ; Pinellia ; chemistry ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry ; Powders ; Rabbits ; Technology, Pharmaceutical ; methods

OBJECTIVETo study the effects of alum, aluminum chloride and aluminum hydroxide on aluminum contents in serum and brain of mice with high performance capillary.

METHOD60 days after the mice were given daily alum, aluminum chloride and aluminum hydroxide with the same aluminum content of 14.25, 57 mg x kg(-1) x d(-1), respectively, the aluminum content in serum and brain of mice were determined with high performance capillary chromatography.

RESULTThe average recoveries of serum aluminum determination was 96.5%-103%. The average recoveries of brain aluminum assay was 92.2%-105.3%. Except control group, serum aluminum increased obviously. Brain aluminum increased in all the large doses groups. 2 weeks after the mice were stopped being given these drugs, serum and brain aluminum recovered to normal level, except aluminum chloride large doses group.

CONCLUSIONThe metabolism and excretion mechanism of aluminum in mice depends on the chemical states of the aluminum compound.

Administration, Oral ; Alum Compounds ; administration & dosage ; pharmacokinetics ; Aluminum ; blood ; metabolism ; Aluminum Compounds ; administration & dosage ; pharmacokinetics ; Aluminum Hydroxide ; administration & dosage ; pharmacokinetics ; Animals ; Brain ; metabolism ; Chlorides ; administration & dosage ; pharmacokinetics ; Electrophoresis, Capillary ; methods ; Male ; Mice

OBJECTIVETo study the effects of concentration, volume and temperature of aluminium water on the change of chromatoghraphic data of processed Rhizoina Arisaematis.

METHODChromatographic fingerprints of processed Radix Pinellia pedatisecta were determined by HPLC, and multivariate analysis was made for data processing.

RESULT AND CONCLUSIONNo change on the whole chromatoghraphic data was observed at different levels of concentrition and volume of aluminium water, while there was a great change at different levels of temperature.

Alum Compounds ; Chromatography, High Pressure Liquid ; methods ; Hot Temperature ; Pinellia ; chemistry ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry ; Technology, Pharmaceutical ; methods ; Temperature

The study about using water sources in diet in community was performed at 3 provinces of Mekong Delta in January 2002. The total number of investigated households were 1639, the samples were collected by investigating 30 groups method. The investigating about major water source using diet showed that on average, about 70% (35-92%) of households used river water, 17.6% (2.0-48%) used tap water and 10.8% (0-20.8%) used rain water. 40% of points used the river water to supply water with community, far latrine-fishpond from 10m, 26% was closed cattle-breeding cage (under 10m). The river water-processing method was alum accumulation, the pasteurization rate without chloramine was nearly 80% and about 20% of households used non-boiled drinking-water. The rate of households used boring well was very low (2-4%), 10% of households entered using processed river water because they were very poor
Water ; epidemiology ; diet ; Alum Compounds ; Chloramines