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PubMed2003

Novel synthetic LPS receptor agonists boost systemic and mucosal antibody responses in mice.

Safe and cost-effective adjuvants are a critical requirement for subunit vaccine development. We report here the in vivo activity of a series of fully synthetic LPS receptor agonists that have been shown to activate NF-kappaB signaling through the Toll-like receptor 4 (TLR4). These compounds boost antibody responses to protein antigens when coadministered at microgram doses in mice. At these dosage levels no adverse effects are observed. Antibody responses are largely IgG1, with enhanced IgG2a, and down-regulated IgE as compared to alum adjuvanted immunization. Stimulation of Th1 is confirmed by enhanced gamma-interferon production after in vitro antigen restimulation of spleen cells from mice immunized with the synthetic adjuvants. The adjuvants are active by both subcutaneous and intranasal routes of vaccine administration, and in the latter case can amplify both serum IgG and serum and mucosal IgA responses. The compounds must be administered at the same site with antigen to boost anti-vaccine antibody. These fully synthetic ligands of the innate immune system offer the potential for use as effective, safe, and nonbiologically-derived adjuvants.

Adjuvants, Immunologic↗
PubMed2002

Effectiveness and mechanism of potassium ferrate(VI) preoxidation for algae removal by coagulation.

Jar tests were conducted to evaluate the effectiveness of potassium ferrate preoxidation on algae removal by coagulation. Laboratory studies demonstrated that pretreatment with potassium ferrate obviously enhanced the algae removal by coagulation with alum [Al2(SO4)3 . 18H2O]. Algae removal efficiency increased remarkably when the water was pretreated with ferrate. A very short time of preoxidation was enough to achieve substantial algae removal efficiency, and the effectiveness was further increased at a prolonged pretreatment time. Pretreatment with ferrate resulted in a reduction of alum dosage required to cause an efficient coagulation for algae removal. The obvious impact of cell architecture by potassium ferrate was found through scanning electron microscopy. Upon oxidation with ferrate. the cells were inactivated and some intracellular and extracelluar components were released into the water, which may be helpful to the coagulation by their bridging effect. Efficient removal of algae by potassium ferrate preoxidation is believed to be a consequence of several process mechanisms. Ferrate preoxidation inactivated algae, induced the formation of coagulant aid, which are the cellular components secreted by algal cells. The coagulation was also improved by increasing particle concentration in water, because of the formation of the intermediate forms of precipitant iron species during preoxidation. In addition, it was also observed that ferrate preoxidation caused algae agglomerate formation before the addition of coagulant, the subsequent application of alum resulted in further coagulation.

Eukaryota↗
PubMed2004

Suramin has adjuvant properties and promotes expansion of antigen-specific Th1 and Th2 cells in vivo.

Aluminum hydroxide and incomplete Freund's adjuvant (IFA) are the only adjuvants approved for human use. Both are T helper 2 (Th2) adjuvants, however, T helper 1 (Th1) immunity is induced if microbial products such as mycobacteria, CpG's, or bacterial toxins are included in the adjuvant preparation. The usefulness of bacterial toxins, such as Pertussis toxin (PT) or Cholera toxin (CT), as adjuvants for human vaccination is limited by toxic side effects and high immunogenicity. Hence, we asked whether or not the adjuvant activity of bacterial toxins on Th1 and Th2 immunity could be mimicked by chemical compounds of small molecular weight and less immunogenicity. In the present study, we show that Suramin, a small molecular weight naphthylurea, which mainly acts on G-proteins and on P2X/P2Y receptors, promotes expansion of hen eggwhite lysozyme (HEL)-specific Th1 and Th2 cells upon immunization of BALB/c mice with HEL in aluminum hydroxide (alum). The results indicated that the adjuvant effects of Suramin on T cell responses were mediated by enhancing the expression of MHC class II and costimulatory molecules on antigen presenting cells (APCs), and by increasing their pro-inflammatory cytokine production. Together, the results suggest that small molecular weight compounds such as Suramin could be used as alternative vaccine adjuvants.

Adjuvants, Immunologic↗
PubMed2006

Chlorination byproducts, their toxicodynamics and removal from drinking water.

No doubt that chlorination has been successfully used for the control of water borne infections diseases for more than a century. However identification of chlorination byproducts (CBPs) and incidences of potential health hazards created a major issue on the balancing of the toxicodynamics of the chemical species and risk from pathogenic microbes in the supply of drinking water. There have been epidemiological evidences of close relationship between its exposure and adverse outcomes particularly the cancers of vital organs in human beings. Halogenated trihalomethanes (THMs) and haloacetic acids (HAAs) are two major classes of disinfection byproducts (DBPs) commonly found in waters disinfected with chlorine. The total concentration of trihalomethanes and the formation of individual THM species in chlorinated water strongly depend on the composition of the raw water, on operational parameters and on the occurrence of residual chlorine in the distribution system. Attempts have been made to develop predictive models to establish the production and kinetics of THM formations. These models may be useful for operational purposes during water treatment and water quality management. It is also suggested to explore some biomarkers for determination of DBP production. Various methods have been suggested which include adsorption on activated carbons, coagulation with polymer, alum, lime or iron, sulfates, ion exchange and membrane process for the removal of DBPs. Thus in order to reduce the public health risk from these toxic compounds regulation must be inforced for the implementation of guideline values to lower the allowable concentrations or exposure.

Acetates↗
PubMed2006

Novel human polysaccharide adjuvants with dual Th1 and Th2 potentiating activity.

Pure soluble, recombinant and synthetic antigens, despite their better tolerability, are unfortunately often much less immunogenic than live or killed whole organism vaccines. Thus, the move towards the development of safer subunit vaccines has created a major need for more potent adjuvants. In particular, there is an urgent need for adjuvants capable of boosting cellular (Th1) immunity but without unacceptable toxicity. The adjuvant activity of aluminium compounds (aluminium phosphate or hydroxide) was first described by Glenny and colleagues in 1926. Surprisingly, despite the description of over one hundred adjuvants in the scientific literature, alum remains the only adjuvant approved for human use in the USA. Unfortunately, alum has no effect on cellular immunity and is faced with increasing concerns regarding potential for cumulative aluminium toxicity. Why then has alum not been replaced in human vaccines? Despite the enormous number of candidates, potency has invariably been associated with increased toxicity, and this more than anything else has precluded their use, particularly in prophylactic vaccines where safety issues are paramount. Hence, there is a major unmet need for a safe efficacious adjuvant capable of boosting cellular plus humoral immunity. The extensive data on inulin-based adjuvants indicate that these are excellent candidates to replace alum as the adjuvant of choice for many vaccines. Particular advantages offered by inulin-based adjuvants is that they induce cellular in addition to humoral immunity and offer excellent safety, tolerability, ease of manufacture and formulation. Thus, adjuvants based on inulin have enormous potential for use in vaccines against both pathogens and cancer.

Adjuvants, Immunologic↗
PubMed2005

Conventional approach for abattoir wastewater treatment.

Detailed physico-chemical studies on abattoir effluent using lime, alum, ferrous sulphate and an anionic polyelectrolyte were tried individually and in combination. Among the coagulants tried, lime resulted in good settling of the sludge. At 400 mg l(-1) of lime dose, the Suspended Solids (SS), Biochemical Oxygen Demand (BOD) and Chemical Oxygen Demand (COD) removals were found to be 41.9%, 38.9% and 36.1%, respectively. Best results were obtained with lime and ferrous sulphate in a combination ratio of 400:100 mg l(-1), and the COD reduction of 36.1% at 400 mg l(-1) of lime, further improved to 56.8%. Lime and alum dose of 400:50 mg l(-1) resulted in an increased COD reduction of 42.6% compared to 36.1% at lime dose of 400 mg l(-1). However, the same lime dose with ferrous sulphate addition of 100 mg l(-1) resulted in an increased COD reduction of 56.8% compared to 36.1%. This is a more efficient option for abattoir wastewater treatment and also cost effective. Ferrous sulphate with anionic polyelectrolyte resulted in good removals. Though it is a costly chemical, the dose needed is just half that of lime and just 0.1 mg l(-1) of anionic polyelectrolyte resulted in good reductions in SS, BOD and COD of 54.2%, 49.6% and 43.8% respectively. Studies indicated that the lime and ferrous sulphate in the combination of 400:100 mg l(-1), and ferrous sulphate and polyelectrolyte in the combination of 100:0.1 mg l(-1) are the two feasible options. Lime in combination with alum can also be applied but resultant sludge volume would be more.

Abattoirs↗
PubMedDate not supplied

Adjuvants in veterinary vaccines: modes of action and adverse effects.

Vaccine adjuvants are chemicals, microbial components, or mammalian proteins that enhance the immune response to vaccine antigens. Interest in reducing vaccine-related adverse effects and inducing specific types of immunity has led to the development of numerous new adjuvants. Adjuvants in development or in experimental and commercial vaccines include aluminum salts (alum), oil emulsions, saponins, immune-stimulating complexes (ISCOMs), liposomes, microparticles, nonionic block copolymers, derivatized polysaccharides, cytokines, and a wide variety of bacterial derivatives. The mechanisms of action of these diverse compounds vary, as does their induction of cell-mediated and antibody responses. Factors influencing the selection of an adjuvant include animal species, specific pathogen, vaccine antigen, route of immunization, and type of immunity needed.

Adjuvants, Immunologic↗
PubMed2001

Removal of hydrocarbons from petrochemical wastewater by dissolved air flotation.

The dissolved air flotation (DAF) method has an important role in the removal of hydrocarbons, as well as in the protection of the biological treatment, which usually follows the DAF. The aims of this study were to evaluate the removal efficiencies of suspended solids, general organic matter, hydrocarbons and phenols by DAF, as influenced by the flocculant type, aluminum sulfate (alum) or a cationic polyelectrolyte. Laboratory batch experiments included chemical flocculation followed by DAF, controlling the flocculant dose and the air to solids ratio. The characterization of the influent and effluent was based on general analysis of organic matter (COD), suspended solids, hydrocarbons and phenols. The influent to all experiments was supplied daily from the outlet of a full scale oil-water gravitational separation unit at a petrochemical complex in Haifa, Israel. The influent contained hydrocarbons in the range of 20 to 77 mg/L. Usually less than 10% were found in "free" form, 70 to 80% were emulsified and 10 to 20% were dissolved. The DAF process enabled us to reduce the general hydrocarbon content by 50 to 90%. The effluent was characterized by stable and uniform levels of suspended solids, and oil, almost without depending on the influent concentrations. The results indicate that the chemical flocculation followed by DAF removed efficiently the emulsified phase, which could be aggregated and separated to the surface. However, it was found that the process could also remove substantial amounts of dissolved organic matter. This mechanism could be explained by the hydrophobic characteristics of some of the substances, which could bind to the solid surfaces. It was found that aggregates created by the flocculation with the cationic polyelectrolite (C-577) could remove up to 40% from the dissolved hydrocarbon. Alum flocs also indicated removal of soluble materials, mainly phenols. The results obtained in this study indicated the possibility to improve the protection of the biological treatment process by preliminary removal of hydrophobic compounds, usually considered as either inhibitory or toxic. This removal can be based on sorption onto aggregates created by chemical flocculation, which can be efficiently removed by dissolved air flotation.

Air↗
PubMed2003

[Preparation of Harris hematoxylin without use of mercury oxide].

The study was carried out with the aim of improvement of Harris' alum hematoxylin formula. In presented modified formula toxic mercuric oxide (2.5 g) is substituted by potassium iodate (0.55 g). Alum hematoxylin solution prepared according to suggested formula retains high quality of original Harris' hematoxylin.

Glycerol↗
PubMed1985

Improved in situ hybridization and G-banding by pretreatment with Denhardt's solution and gelatin-chrome alum.

Various pretreatments of metaphase spreads were examined to obtain optimal DNA labelling patterns while maintaining chromosome integrity during in situ hybridization procedures. Preparations of African green monkey (AGM) chromosomes fixed in methanol-acetic acid (CV-1 cell line) were treated by coating with Denhardt's solution, dilute gelatin-chrome alum, nonfat instant dry milk dissolved in saline-citrate solution (SSC) and/or acetylation prior to denaturation of chromosomal DNA in 70% formamide-2 X SSC for 2 min at 70 degrees C. A 3H-labelled, cloned DNA fragment of the highly repetitive AGM component alpha DNA was hybridized to the chromosomes by incubation at 45 degrees C for 16 h. Treatment with gelatin-chrome alum prior to denaturation greatly improved chromosome morphology and decreased background, but reduced pericentromeric labelling. Sequential treatment with 5 X Denhardt's solution followed by gelatin-chrome alum resulted in enhanced specificity of labelling and excellent chromosome morphology, as well as reduced levels of background. Acetylation had little effect after pretreatment with gelatin-chrome alum, but reduced background levels after pretreatment with Denhardt's solution. Chromosomes treated with Denhardt's solution plus gelatin-chrome alum can be routinely G-banded using trypsin after in situ hybridization.

Animals↗
PubMed1999

A prime-boost regime that combines Montanide ISA720 and Alhydrogel to induce antibodies against the HIV-1 derived multiepitope polypeptide TAB9.

A phase I clinical trial with the HIV-1-derived multi-epitope polypeptide (MEP) TAB9 in the oil adjuvant Montanide ISA720 (M-ISA720) was recently performed. Although severe local reactions were reported after the second and third injections of this vaccine candidate, the first inoculation was well tolerated. In this article we evaluated a prime-boost regime consisting of one inoculation of TAB9 in M-ISA720 followed by a booster with the same antigen in aluminum hydroxide. This combination of adjuvants elicited similar antibody levels in rabbits than the traditional two-dose schedule with M-ISA720. A control group injected three times with TAB9 in aluminum hydroxide developed markedly lower antibody titers. These results showed that although oil adjuvants are better than alum for priming the immune system for antibody production against TAB9, both kinds of adjuvants can be equally effective in booster immunizations. Therefore, by using the more reactogenic oil adjuvant only for priming, we should be able to eliminate the undesirable reactions characteristic of these compounds while achieving equivalent levels of specific antibodies.

AIDS Vaccines↗
PubMed2006

Removal and inactivation of Cryptosporidium and microbial indicators by a quaternary ammonium chloride (QAC)-treated zeolite in pilot filters.

A set of pilot filters packed with Zeolite filter media treated with a quaternary ammonium chloride (QAC) were evaluated to verify the proof of concept of their combined antimicrobial capabilities. Escherichia coli was removed and inactivated the most (2.83 log), followed by MS-2 (2.75 log), Klebsiella terriena (2.21 log), PRD-1 (1.95 log), Chlorella vulgaris (1.92 log), and Cryptosporidium parvum oocysts (1.78 log). Especially, inactivation of C. parvum oocysts (1.19 log) was higher than physical removal (0.54 log). The data suggest that QAC-treated Zeolite in the pilot filters has microbial inactivation capabilities and may have useful applications in other types of filter media.

Animals↗
PubMed2005

Mouse strain specificity of the IgE response to the major allergens of Phleum pratense.

BACKGROUND: IgE immune responses against major allergens from Phleum pratense in low- and high-responder mouse strains were compared and the influence of alum was assessed, in order to evaluate the effect of the genetic background and adjuvants on IgE reactivity in a mouse model for P. pratense allergy. METHODS: Different mouse strains and F1 offspring were sensitized with P. pratense pollen extract. Serum IgE levels, the induction of specific IgE antibodies and immediate cutaneous hypersensitivity reactions were monitored by ELISA, Western blot and a skin test, respectively. RESULTS: All mouse strains investigated mounted an IgE response and exhibited a positive skin test to pollen extract. Differences were seen in the level of total serum IgE and in specific IgE reactivity to different major allergens of P. pratense. Notable differences were seen in IgE reactivity and immediate hypersensitivity against Phl p 1, which were only observed in SJL/j mice. The foremost influence of alum was on total IgE production levels. CONCLUSIONS: Alum is not necessary as an adjuvant to elicit IgE reactivity against the clinically relevant allergens of P. pratense, since even low-responder mouse strains mounted a hypersensitivity reaction after sensitization without the adjuvant using otherwise identical sensitization strategies. Moreover, when analyzing the allergenicity of a compound, the hypersensitivity response of different mouse strains should be considered, as implicated by the differential results obtained for IgE reactivity against Phl p 1. Lastly, a genetic component may be involved in IgE reactivity to Phl p 1.

Allergens↗
PubMed1992

[Immunogenicity studies in experimental animals immunized with a low-molecular antigen alone and the antigen plus adjuvants].

The present studies were undertaken to clarify the immunogenicity evoked in four species, the guinea pig, rabbit, F344 rat and A/J mouse, immunized with a low-molecular antigen (TNBS) alone, TNBS plus Alum and TNBS plus FCA. Each species was divided into three groups: TNBS alone sc group, TNBS plus Alum ip groups (one and 3 times sensitization) and TNBS plus FCA sc groups (one and 3 times sensitization), and immune responses to TNBS were estimated by the assay systems of humoral immunoreactions (HA.PCA.SANA.Arthus) and cellular immunoreaction (DTH by the intracutaneous method & application method). All of the species showed significantly positive humoral immune responses in the TNBS alone sc group, the TNBS plus Alum ip groups and in the TNBS plus FCA sc groups. Nearly all of the guinea pigs and rabbits displayed positive cellular immune response (DTH by the intracutaneous method), while such immune response was never recognized in the rat groups. These results suggest that TNBS is a useful model compound as a positive control for the antigenicity tests of novel drugs.

Adjuvants, Immunologic↗