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PubMed2004

Pilot scale microfiltration-coagulation for treatment of retention pond water.

An evaluation of two commonly used coagulants, alum and ferric chloride was conducted to treat retention pond water using microfiltration. To determine the effectiveness of these coagulants in removing turbidity, color, and total suspended solids two different sets of the experiments were performed. Preliminary test was carried out to evaluate the optimum dosages of coagulants. Optimum turbidity removal was achieved with a 4 and 20 mg/L dosage for ferric chloride and alum, respectively. Generally, coupling microfiltration with coagulation using both alum and ferric chloride exhibited excellent effectiveness for turbidity, color, and total suspended solids removal. The efficiency for alum and ferric chloride for turbidity removal were 96 and 98%, respectively, which was greater than 89% removal using microfiltration alone. Furthermore, microfiltration only demonstrated 81 and 83% removal efficiency for color and total suspended solids removal, respectively. However, microfiltration-coagulation using alum and ferric chloride resulted about 83 and 93% color removal, and 92 and 94% total suspended solids removal, respectively.

Alum Compounds↗
PubMed2001

Monitoring the retention of a protein antigen in complete Freund's adjuvant, alum, and pluronic F-127 gel formulations by X-ray fluorescence.

Adjuvants function by protecting antigens from rapid degradation or dispersal. The effectiveness of experimental adjuvants can be assessed by measuring antibody titers to the antigen of interest or, less frequently, by evaluating the retention and distribution of antigen at the application site. In this study, we used X-ray fluorescence (XRF) to monitor the release of an iodinated protein (I-bovine serum albumin) from several adjuvant formulations after its subcutaneous injection in rats. The interaction of the tagged antigen with an external Am-241 source leads to the emission of iodine X-rays from the application site; the number of these X-rays is proportional to the concentration of the protein remaining at the injection site. The disappearance of the iodine X-rays, and hence the antigen, from the injection site followed first-order kinetics for all adjuvant formulations tested; mean half-life values were as follows: in 50% Freund's adjuvant, 17.1 +/- 1.1 h; in 4-hour-old 25% Alum, 11.78 +/- 0.08 h; in 4-h-old 50% Alum, 13.2 +/- 2 h; in 3-day-old 50% Alum, 15.8 +/- 1.5 h; and in 240 mg/mL Pluronic F-127, 7.9 +/- 0.7 h. We conclude that XRF is an easy, reliable, noninvasive method to monitor the retention of antigens in these adjuvant solutions.

Alum Compounds↗
PubMed1955

Studies on antibody production. III. The alum granuloma.

After subcutaneous injection of hen's ovalbumin or diphtheria toxoid precipitated with aluminum phosphate, the production of antibody, as judged by the presence in the tissues of antibody-containing cells, proceeds partly within the regional lymphatic glands and partly in the granulation tissue surrounding the nodule which develops at the site of injection. The first production of antibody takes place in the regional lymphatic gland and antibody production in the local granuloma becomes apparent only from 14 days onwards (rabbit). Antibody-containing plasma cells were demonstrated in the local granuloma up to 7 weeks. Antibody-containing cells in the regional lymphatic glands reach maximum numbers at 2 weeks following injection and decrease thereafter to few cells at 5 weeks. The adjuvant effect of the aluminum phosphate is interpreted as due partly to the delay in absorption of antigen from the local site of its injection which results in prolongation of stimulation of cells within the regional lymphatic glands, and partly to the production of a local granuloma which contains antibody-producing plasma cells.

Adjuvants, Immunologic↗
PubMed2000

Antigen-independent appearance of recombination activating gene (RAG)-positive bone marrow B cells in the spleens of immunized mice.

Splenic B lineage cells expressing recombination activation genes (RAG(+)) in mice immunized with 4-hydroxy-3-nitrophenyl-acetyl coupled to chicken gamma-globulin (NP-CGG) and the adjuvant aluminum-hydroxide (alum) have been proposed to be mature B cells that reexpress RAG after an antigen encounter in the germinal center (GC), a notion supported by findings of RAG expression in peripheral B lymphocyte populations activated in vitro. However, recent studies indicate that these cells might be immature B cells that have not yet extinguished RAG expression. Here, we employ RAG2-green fluorescent protein (GFP) fusion gene knock-in mice to show that RAG(+) B lineage cells do appear in the spleen after the administration of alum alone, and that their appearance is independent of T cell interactions via the CD40 pathway. Moreover, splenic RAG(+) B lineage cells were detectable in immunized RAG2-deficient mice adoptively transferred with bone marrow (BM) cells, but not with spleen cells from RAG(+) mice. Although splenic RAG(+) B cells express surface markers associated with GC B cells, we also find the same basic markers on progenitor/precursor BM B cells. Finally, we did not detect RAG gene expression after the in vitro stimulation of splenic RAG(-) mature B cells with mitogens (lipopolysaccharide and anti-CD40) and cytokines (interleukin [IL]-4 and IL-7). Together, our studies indicate that RAG(+) B lineage cells from BM accumulate in the spleen after immunization, and that this accumulation is not the result of an antigen-specific response.

Adoptive Transfer↗
PubMed2006

Antigen targeting to dendritic cells elicits long-lived T cell help for antibody responses.

Resistance to several prevalent infectious diseases requires both cellular and humoral immune responses. T cell immunity is initiated by mature dendritic cells (DCs) in lymphoid organs, whereas humoral responses to most antigens require further collaboration between primed, antigen-specific helper T cells and naive or memory B cells. To determine whether antigens delivered to DCs in lymphoid organs induce T cell help for antibody responses, we targeted a carrier protein, ovalbumin (OVA), to DCs in the presence of a maturation stimulus and assayed for antibodies to a hapten, (4-hydroxy-3-nitrophenyl) acetyl (NP), after boosting with OVA-NP. A single DC-targeted immunization elicited long-lived T cell helper responses to the carrier protein, leading to large numbers of antibody-secreting cells and high titers of high-affinity antihapten immunoglobulin Gs. Small doses of DC-targeted OVA induced higher titers and a broader spectrum of anti-NP antibody isotypes than large doses of OVA in alum adjuvant. Similar results were obtained when the circumsporozoite protein of Plasmodium yoelii was delivered to DCs. We conclude that antigen targeting to DCs combined with a maturation stimulus produces broad-based and long-lived T cell help for humoral immune responses.

Adjuvants, Immunologic↗
PubMed2001

Water disinfection for international and wilderness travelers.

Acquisition of waterborne disease is a substantial risk for international travelers to countries with inadequate sanitation facilities. It also poses smaller but still significant risks for wilderness travelers who rely on surface water in developed countries with low rates of diarrheal illness, such as the United States. This article reviews the etiology and risks associated with waterborne disease that might be encountered by both types of travelers. It also summarizes--and makes recommendations for--the various water-treatment methods available to travelers for reducing their risk of contracting waterborne disease.

Alum Compounds↗
PubMed2003

Protection against group A streptococcus by immunization with J8-diphtheria toxoid: contribution of J8- and diphtheria toxoid-specific antibodies to protection.

A conformationally constrained, minimally conserved peptide from the M protein of group A streptococcus (GAS) has been defined. It consists of 12 amino acids from the C-repeat region within a non-M protein helix-forming sequence and is referred to as "J8." Here, we investigate the immunogenicity of a J8-diphtheria toxoid (DT) conjugate adjuvanted with the human-compatible adjuvants, SBAS2 and alum, and demonstrate that it is capable of inducing opsonic antibodies and can protect outbred mice from virulent challenge. In a range of experiments, protection correlated with the titer of J8-specific antibodies and not with the induction of J8-specific T cells. However, DT-specific antibodies (as well as J8-specific antibodies) were shown to stain the surface of fixed GAS and to be capable of opsonizing live organisms. DT may be an ideal carrier protein for J8 and other GAS peptides for GAS vaccines.

Adjuvants, Immunologic↗
PubMed2004

Protection against congenital cytomegalovirus infection and disease in guinea pigs, conferred by a purified recombinant glycoprotein B vaccine.

Glycoprotein B (gB) has emerged as a subunit-vaccine candidate for congenital cytomegalovirus (CMV) infection, a major public health problem. The present study evaluated a cloned, recombinant gB vaccine in the guinea pig cytomegalovirus (GPCMV) model of congenital infection. Guinea pigs were immunized with gB, which was coadministered with either Freund's adjuvant or alum. All gB-immunized dams had enzyme-linked immunosorbent-assay and neutralizing-antibody responses, with significantly higher titers in the gB/Freund's group. Pregnant dams were challenged with GPCMV subcutaneously during the 3rd trimester. Maternal DNAemia on day 10 after infection trended lower in gB-immunized dams than in control animals, with significant reductions in the gB/Freund's group. Vaccination resulted in a highly significant reduction in pup mortality. For the gB-vaccine groups, pup mortality was significantly lower, and reduced rates of GPCMV transmission were noted, for dams immunized with gB and Freund's adjuvant, compared with dams immunized with gB and alum. These are the first data indicating that a recombinant gB vaccine protects against congenital CMV infection and disease.

Adjuvants, Immunologic↗
PubMed2006

Vaccines for seasonal and pandemic influenza.

Seasonal influenza continues to have a huge annual impact in the United States, accounting for tens of millions of illnesses, hundreds of thousands of excess hospitalizations, and tens of thousands of excess deaths. Vaccination remains the mainstay for the prevention of influenza. In the United States, 2 types of influenza vaccine are currently licensed: trivalent inactivated influenza vaccine and live attenuated influenza vaccine. Both are safe and effective in the populations for which they are approved for use. Children, adults <65 years of age, and the elderly all receive substantial health benefits from vaccination. In addition, vaccination appears to be cost-effective, if not cost saving, across the age spectrum. Despite long-standing recommendations for the routine vaccination of persons in high-priority groups, US vaccination rates remain too low across all age groups. Important issues to be addressed include improving vaccine delivery to current and expanded target groups, ensuring timely availability of adequate vaccine supply, and development of even more effective vaccines. Development of a vaccine against potentially pandemic strains is an essential part of the strategy to control and prevent a pandemic outbreak. The use of existing technologies for influenza vaccine production would be the most straightforward approach, because these technologies are commercially available and licensing would be relatively simple. Approaches currently being tested include subvirion inactivated vaccines and cold-adapted, live attenuated vaccines. Preliminary results have suggested that, for some pandemic antigens, particularly H5, subvirion inactivated vaccines are poorly immunogenic, for reasons that are not clear. Data from evaluation of live pandemic vaccines are pending. Second-generation approaches designed to provide improved immune responses at lower doses have focused on adjuvants such as alum and MF59, which are currently licensed for influenza or other vaccines. Additional experimental approaches are required to achieve the ultimate goal for seasonal and pandemic influenza prevention--namely, the ability to generate broadly cross-reactive and durable protection in humans.

Adjuvants, Immunologic↗
PubMed1997

Immunogenicity of two doses of yeast recombinant hepatitis B vaccine in healthy older adults.

To determine the immunogenicity of two doses of yeast recombinant hepatitis B virus (HBV) vaccine containing surface (S) protein, an open-label, multicenter trial was conducted in 199 healthy HBV-seronegative adults > or = 40 years old. Volunteers were randomly assigned to 1 of 5 groups to receive a total of three 10-microg doses, at 0, 1, and 6 months, or a total of two doses of 20 microg and 10 microg, 20 microg and 20 microg, 40 microg and 10 microg, or 40 microg and 20 microg at 0 and 6 months. The 40-microg/20-microg regimen elicited the highest rate of seroprotection (96.2%), with a geometric mean titer of antibody against the S protein of 369 mIU/mL, not significantly different from the 536 mIU/mL achieved with three doses. These results suggest that a two-dose regimen can achieve seroprotection similar to that of the three-dose regimen. Whether a shorter interval can be used or a booster dose will be needed later to confer durable immunity are unknown.

Adult↗
PubMed2006

Review: novel nonviral delivery approaches for interleukin-12 protein and gene systems: curbing toxicity and enhancing adjuvant activity.

It has become increasingly apparent that the ability to generate an optimal host immune response requires effective cross talk between the innate and adaptive components of the immune system. Pro-inflammatory cytokines, in particular those that can induce a danger signal, often called signal 3, are crucial in this role of initiating and augmenting the presentation of exogenous antigen to T cells by dendritic cells. Interleukin-12 (IL-12) in particular has been defined as a "signal 3" cytokine required for the antigen cross priming. Given this unique interactive function, a significant amount of work has been performed to define possible therapeutic applications for IL-12. Systemic IL-12 administration can clearly act as a potent adjuvant for postvaccination T cell responses in a variety of diseases. As an example, in the cancer setting, systemic IL-12 is capable of suppressing tumor growth, metastasis, and angiogenesis in vivo. IL-12, however, has been associated with significant dose- and schedule-dependent toxicity in early clinical trials, results that have proven to be a major obstacle to its clinical application. Recent research has focused on decreasing the toxicity of IL-12 using different delivery approaches, including virus-based and gene-modified cell-based delivery. Although effective, these approaches also have limitations, including the generation of neutralizing antibodies, in addition to lacking the simplicity and versatility required for universal clinical application. Thus, there is a significant interest in the development of alternative delivery approaches for IL-12 administration that can overcome these issues. Several nonviral delivery approaches for IL-12 protein or gene expression vectors are being defined, including alum, liposomes, and polymer-based delivery. These developing approaches have shown promising adjuvant effects with significantly lessened systemic toxicity. This article discusses the potential capabilities of these nonvirus-based IL-12 delivery systems in different disease settings, including allergy, infection, and cancer.

Adjuvants, Immunologic↗
PubMed1994

Interactions of astringent substances.

Two-component mixtures of astringent materials were rated for perceived intensity of astringent and taste attributes over time. Components included alum (a complex salt), gallic acid (the monomeric component of hydrolyzable tannins), catechin (the monomeric component of condensed tannins) and citric acid. Mixtures of alum and gallic acid showed mixture suppression, in that the 50/50 mixture was less intense than either component in astringency, drying, roughing and puckery/drawing sensations. Suppression was seen at concentration levels producing moderate to strong astringency but was absent or less pronounced at lower concentration levels. A similar pattern held for citric acid, although the suppressive effects were less pronounced. Catechin and gallic acid mixtures were additive. Sensory interactions between astringent materials appears to depend on the substances involved and their concentrations (or intensity levels).

Adult↗
PubMedDate not supplied

Vaccine adjuvants.

Nonreplicating, purified subunit or synthetic viral vaccines of the future are likely to be weak immunogens that will require immunopotentiation if they are to be effective. These marginal vaccines could be improved by combination with potent and safe immunologic adjuvants. The use of adjuvants should also reduce the amount of purified antigen required for successful immunization, thus making vaccine production more economical and more feasible. It may be possible to combine the recently developed relatively nontoxic synthetic immunoregulators of low molecular weight with antigens in order to modulate preselected compartments of the immune system. To date, the question of adjuvant safety has not been resolved and represents the major obstacle to the orderly development of adjuvanted vaccines. The fear of inducing cancer and other immediate or long-term perturbations of the immune system must be patently and rationally overcome by basic and applied experimentation and by the development of appropriate guidelines for studies in humans.

Adjuvants, Immunologic↗