Current Pharmaceutical Biotechnology - Volume 4, Issue 2, 2003

The potential therapeutic activity of a killer toxin produced by the yeast Pichia anomala (PaKT) characterized by its wide spectrum of antimicrobial activity has been exploited through the simulation of its interaction with the specific cell wall receptor (KTR) of PaKTsensitive microorganisms by the idiotypic network. Killer antiidiotypes (PaKTantiId) produced by idiotypic vaccination with a PaKT-neutralizing monoclonal antibody have proven to confer active and passive immunoprotection in experimental models of systemic and vaginal candidiasis. PaKTantiId-like human anti-KTR antibodies are naturally produced in infections caused by PaKT-sensitive microorganisms. PaKTantiId in its monoclonal and recombinant formats as well as expressed on human commensal bacteria have shown microbicidal activity in vitro and a therapeutic effect in experimental models of infection caused by PaKT-sensitive microorganisms. New perspectives of idiotypic vaccination and antiidiotypic antibiotic therapy and biotechnological approaches to the production of trandisease idiotypic vaccines and wide-spectrum antiidiotypic antibiotics (killer mimotopes) will be discussed as effective tools to fight epidemiologically important mucosal and systemic microbial infections.

After 200 years of practice, vaccinology has proved to be very effective in preventing infectious diseases. However, several human and animal pathogens exist for which vaccines need to be improved or simply have not yet been discovered. The era of molecular genetic has given a new breath for vaccine development with the achievement of the “Third Generation of Vaccines”: the DNA vaccine. In this article, we reviewed strategies that have been used to improve and modulate the immune response induced by DNA vaccines, using as a model the intracellular bacterial pathogen Brucella abortus. First, we described different approaches used to isolate and to identify genes that encode potential immunogens. Secondly, we reported the use of cytokine genes and genetic adjuvants that could improve the immunogenicity of target genes. And finally, we discussed the “Expression Library Immunization”-(ELI) strategy and the recent results obtained against Brucella abortus infection.

Increasing attention has been paid to technology used for the delivery of genetic materials into cells for gene therapy and the generation of genetically engineered cells. So far, viral vectors have been mainly used because of their inherently high transfection efficiency of gene. However, there are some problems to be resolved for the clinical applications, such as the pathogenicity and immunogenicity of viral vectors themselves. Therefore, many research trials with non-viral vectors have been performed to enhance their efficiency to a level comparable to the viral vector. Two directions of these trials exist: material improvement of non-viral vectors and their combination with various external physical stimuli. This paper reviews the latter research trials, with special attention paid to the enhancement of gene expression by ultrasound (US). The expression level of plasmid DNA by various cationized polymers and liposomes is promoted by US irradiation in vitro as well as in vivo. This US-enhanced expression of plasmid DNA will be discussed to emphasize the technical feasibility of US in gene therapy and biotechnology.

Insulin-like growth factor-I (IGF-I) is a naturally occurring single chain polypeptide of 7649 Da that is produced primarily in the liver. The metabolic activities of IGF-I are similar to those of insulin and its effects on growth, development, regeneration and metabolism have been widely studied. Indeed, IGF-I is currently being used clinically for the treatment of growth related disorders and its therapeutic value is also being evaluated in diabetes, IGF-I-induced neuroprotection, and in promoting bone healing. However, like many other peptides, IGF-I has a short biological half-life and is rapidly removed from circulation following systemic administration. In the vascular system, this is normally compensated for by the association of IGF-I with IGF-binding proteins (IGFBPs), that also appear to regulate the activities of IGF-I.Here, we describe the biopharmaceutical properties of different parenteral formulations of IGF-I. The pharmaceutical characteristics of conventional formulations such as aqueous IGF-I solutions are compare with new controlled release formulations such as multivesicular liposomes, osmotic minipumps, and poly (DL-lactic-co-glycolic) acid (PLGA) microspheres.

Hepatitis B (HB) in haemodialysis patients results in morbidity and mortality, through chronicity, which leads to cirrhosis and liver carcinoma, even after renal transplantation. Hepatitis B vaccination is protective against HB virus infection.Suppressed immunity in renal failure leads to low HB vaccination success rates. Uremia, inadequate dialysis, use of low biocompatibility dialysis material, hyperparathyroidism, anemia, iron overload and malnutrition are all factors contributing to depressed immunity.Renal failure, associated with chronic inflammation, leads to impaired monokine production which results in decreased immunity. This impairment could result from defective HLA-DR B7-2 expression on monocytes. Hepatitis B vaccination non-responders express increased levels of HLA class II alleles (T-cell immune response modulators) DRB1 01 (DR1) and DRB1 15 (DR15).Various methods have been used to enhance the immune response to HB vaccination such as recombinant adjuvants, thymopentine, IL-2, levamisole and GM-CSF: they have produced variable results. Better dialysis biocompatibility and adequacy have also been conducted to overcome this low immune response. Response to conventional intramuscular HB vaccination is considered an index of adequate dialysis and low inflammatory state, both associated with better cardiovascular outcome and survival. HB vaccination reinforcement techniques evolved from an initial intramuscular double / multiple-dosing regimen to more frequent intradermal smaller dose injection. This newer regimen achieves a higher and almost complete seroconversion rate, although frequent boosters shots are necessary to maintain protective levels. Experience with pre-S1 / S2, third generation, vaccines is limited and they have not been proven to be more effective than intradermally administered S antigens. Recombinant HB vaccines, intradermally administered, have been shown to elicit an immune response in all renal failure patients. Additionally the use of recombinant erythropoietin treatment to correct anemia contributes to this success.