Influence of elemental impurities in aluminum hydroxide adjuvant on the stability of inactivated Japanese Encephalitis vaccine, IXIARO®.

Aluminum hydroxide is a critical raw material in the production of many vaccines. It is used as an adjuvant in the formulation of the final bulk vaccine, and for this it must meet the specifications of the European Pharmacopeia Monograph. We investigated whether vaccine stability was affected by the presence of trace amounts of elemental impurities in commercially available aluminum hydroxide.

Effect of adjuvants on the humoral immune response to congopain in mice and cattle.

Background: We investigated several adjuvants for their effects on the humoral immune response in both mice and cattle using the central domain of congopain (C2), the major cysteine protease of Trypanosoma congolense, as a model for developing a vaccine against animal trypanosomosis. The magnitude and sustainability of the immune response against C2 and the occurrence of a booster effect of infection, an indirect measure of the presence of memory cells, were determined by ELISA, while spectrofluorometry was used to determine and measure the presence of enzyme-inhibiting antibodies.

Results: Mice immunized with recombinant C2 in TiterMax™, Adjuphos™, purified saponin Quil A™ or Gerbu™ showed the best response according to the evaluation criteria and the latter three were chosen for the cattle vaccination study.

Progress in understanding adjuvant immunotoxicity mechanisms.

Over the last twenty years research has provided an important insight into the mechanisms responsible for the immunotoxicity of both local and systemic adverse reactions following the use of immunostimulating drugs and adjuvants. In this article we provide an update of the present knowledge relating to the various parameters and reactants of the immune system at the cellular as well as molecular level that are believed to play a key role in reactogenicity. We discuss evidence obtained from observations in vitro, in vivo in animal models and from clinical applications, including adjuvants used in large scale vaccination today.

Experiences of the new role of advanced practice nurses in Swedish primary health care--a qualitative study.

Experiences of the new role of advanced practice nurses in Swedish primary health care-A qualitative study The aim of this study was to investigate and describe the experiences of the first advanced practice nurses (APNs), a new profession for Swedish health care, and of their supervising general practitioners (GPs), regarding the new role and scope of practice of APNs in primary health care. Individual interviews were conducted with the four first APNs and one focus group interview was conducted with five supervising physicians. The material was transcribed verbatim and analysed using latent content analysis.

Aluminum adjuvants: preparation, application, dosage, and formulation with antigen.

Important new knowledge about the effect of aluminum adjuvants on the immune response in terms of their impact on cytokine profiles, uptake by antigen-presenting cells (APC), and surface marker expression has been published in recent years. However, although the knowledge about these adjuvants is thus more comprehensive now than ever before, the user is often still confined to a more empirical approach when confronted with practical issues when it comes to the handling and use of these adjuvants. In this chapter we have given focus to the user's perspective, discussing practicalities like dosage, temperature stability, relevant monographs, and preparation with antigen.

Aluminium compounds for use in vaccines.

Aluminium adjuvants are the most widely used adjuvants in both human and veterinary vaccines. These adjuvants have been used in practical vaccination for more than 60 years and are generally recognized as safe and as stimulators of Th2 immunity. The present review gives a short introduction to the pioneering research at the start of the use of aluminium compounds as adjuvants, including references on the chemistry of these compounds.

Aluminium adjuvants--in retrospect and prospect.

Aluminium compounds have been used as adjuvants in practical vaccination for more than 60 years to induce an early, an efficient and a long lasting protective immunity and are at present the most widely used adjuvants in both veterinary and human vaccines. Although the last two decades of systematic research into the nature of these adjuvants has contributed significantly to understanding their nature and their limitations as Th2 stimulators the more detailed mode of action of these adjuvants is still not completely understood. We have a comprehensive record of their behaviour and performance in practical vaccination, but an empirical approach to optimising their use in new vaccine formulations is still to some extent a necessity.

Codelivery of a DNA vaccine and a protein vaccine with aluminum phosphate stimulates a potent and multivalent immune response.

The study explores the possibility of efficiently codelivering DNA vaccines and protein-based vaccines by formulation with aluminum phosphate (AlPO4). When mixed with aluminum adjuvants, plasmid DNA bound tightly onto aluminum hydroxide [Al(OH)3] but not to AlPO4. Different doses of DNA vaccines formulated with AlPO4 [but not Al(OH)3] induced enhanced humoral responses and supported priming of MHC class I restricted cellular immunity.

ESAT-6 subunit vaccination against Mycobacterium tuberculosis.

The ESAT-6 antigen from Mycobacterium tuberculosis is a dominant target for cell-mediated immunity in the early phase of tuberculosis (TB) in TB patients as well as in various animal models. The purpose of our study was to evaluate the potential of ESAT-6 in an experimental TB vaccine. We started out using dimethyl dioctadecylammonium bromide (DDA), an adjuvant which has been demonstrated to be efficient for the induction of cellular immune responses and has been used successfully before as a delivery system for TB vaccines.

Stability of aluminium-containing adjuvants to autoclaving.

Aluminium phosphate adjuvant remained amorphous when autoclaved for 30 or 60 min at 121 degrees C. However, deprotonation and dehydration reactions occurred as evidenced by a decrease in the pH. The protein adsorption capacity, rate of acid neutralization at pH 2.

The Production of Polyclonal Antibodies in Laboratory Animals. The Report and Recommendations of ECVAM Workshop 35.

This is the report of the thirty-fifth of a series of workshops organised by the European Centre for the Validation of Alternative Methods (ECVAM). ECVAM's main goal, as defined in 1993 by its Scientific Advisory Committee, is to promote the scientific and regulatory acceptance of alternative methods which are of importance to the biosciences and which reduce, refine or replace the use of laboratory animals. One of the first priorities set by ECVAM was the implementation of procedures which would enable it to become well informed about the state-of-the-art of non-animal test development and validation, and the potential for the possible incorporation of alternative tests into regulatory procedures.

Adjuvant modulation of immune responses to tuberculosis subunit vaccines.

Mice were immunized with experimental subunit vaccines based on secreted antigens from Mycobacterium tuberculosis in a series of adjuvants, comprising incomplete Freund's adjuvant (IFA), dimethyl dioctadecyl ammoniumbromide (DDA), RIBI adjuvant, Quil-A saponin, and aluminum hydroxide. Immune responses induced by these vaccines were characterized by in vitro culture of primed cells, PCR analysis for cytokine mRNA, detection of specific immunoglobulin G isotypes induced, and monitoring of protective immunity to tuberculosis (TB). The study demonstrated marked differences in the immune responses induced by the different adjuvants and identified both IFA and DDA as efficient adjuvants for a TB subunit vaccine.

Adjuvanticity of dimethyl dioctadecyl ammonium bromide, complete Freund's adjuvant and Corynebacterium parvum with respect to host immune response to coccidial antigens.

Immune response of chickens to Eimeria was investigated following immunization with coccidial antigens in combination with various immunological adjuvants. The adjuvanticity of dimethyl dioctadecyl ammonium bromide (DDA) was comparable to that of two other adjuvants known to stimulate cell-mediated immunity: complete Freund's adjuvant (CFA) and Corynebacterium parvum. However, DDA is considered less toxic than CFA and appeared to evoke longer-lasting immunity than C.

Adjuvants--a balance between toxicity and adjuvanticity.

Adjuvants have been used to augment the immune response in experimental immunology as well as in practical vaccination for more than 60 years. The chemical nature of adjuvants, their mode of action and the profile of their side effects are highly variable. Some of the side effects can be ascribed to an unintentional stimulation of different mechanisms of the immune system whereas others may reflect general adverse pharmacological reactions.

Ultrasonic degradation of DNA.

Different results are obtained when DNA in aqueous solution and DNA in biological tissue are exposed to ultrasound. At intensities of ultrasound comparable to those applied clinically, ultrasonication is able to degrade purified DNA in aqueous solution, making ultrasonication a useful tool for preparing DNA fragments in vitro. Ultrasonic degradation of DNA in solution occurs by breaking hydrogen bonds and by single-strand and double-strand ruptures of the DNA helix.