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Vaccine Preparation (vaccine + preparation)
Selected Abstracts,-Amyloid immunization approaches for Alzheimer's diseaseDRUG DEVELOPMENT RESEARCH, Issue 2 2002Bruno P. Imbimbo Abstract Alzheimer's disease (AD) represents the third leading cause of death in the U.S. and the leading cause of dementia in the elderly population. Until recently, there was little hope of efficiently combating this devastating disease. The deposition of ,-amyloid (A,) is the major pathological hallmark of AD brains. Genetic, biochemical, and pharmacological evidence support the hypothesis that A, plays a key role in the development of the disease. Thus, in the last 5 years a number of pharmacological strategies have been developed to interfere with the A, cascade. The most revolutionary of these approaches was proposed in 1999 by scientists at Elan Pharmaceuticals, which immunized against A, transgenic mice with spontaneously developing A, pathology. The immunization was achieved by subcutaneous injections of a preaggregated form of the synthetic human 42-amino acid A, emulsified with Freund's adjuvant, an immune stimulant. The vaccination caused a near complete inhibition of A, plaque formation in younger animals and a marked reduction of the A, burden in older animals. The effects on A, plaques were accompanied by a reduction of A,-associated astrogliosis and neuritic dystrophy. These results were later confirmed by other groups with similar vaccination protocols, which also demonstrated that the A, immunization of transgenic animals normalize or reduce the cognitive impairment associated with A, pathology. Interestingly, effective removal of brain A, plaques was also obtained by peripherally administering A, antibodies. The mechanism with which the vaccine increases A, clearance is not fully understood. Centrally, the vaccine appears to activate A, phagocytosis by microglial monocytes. Peripherally, serum A, antibodies bind and sequester A,, thus altering its equilibrium between CNS and plasma. The dramatic results obtained in animal models of AD raised unprecedented hopes for both a preventive and a curative intervention for this devastating disorder. A vaccine preparation for human use (AN-1792) composed of preaggregated human A,42 peptide and a highly purified saponin derivative (QS-21) was developed by Elan Pharmaceuticals and Wyeth Ayerst and tested in AD patients. Unfortunately, a Phase IIa study aimed at evaluating the safety and immunological activity of AN-1792 in 360 AD patients was discontinued because 15 subjects receiving the vaccine developed serious signs of CNS inflammation. Both central activation of cytotoxic T cells and autoimmune reactions were proposed as potential mechanisms of toxicity. Other therapeutic A, vaccination strategies are being pursued, including immuno-conjugates and monoclonal antibodies. The future of these and other A, immunization approaches depend on a clear understanding of the mechanism of A, clearance and additional insight into the role of inflammation in the AD brain. Drug Dev. Res. 56:150,162, 2002. © 2002 Wiley-Liss, Inc. [source] Computer-assisted 2-D agarose electrophoresis of Haemophilus influenzae type B meningitis vaccines and analysis of polydisperse particle populations in the size range of viruses: A reviewELECTROPHORESIS, Issue 4 2007Dietmar Tietz Dr. Abstract When protein,polysaccharide conjugated vaccines were first developed for the immunization of small children against meningitis caused by infection with Haemophilus influenzae type b (Hib), the vaccine preparations varied in immunogenicity. Testing for immunogenicity was time-consuming and alternative analytical procedures for determining vaccine quality were unsatisfactory. For example, due to the very high molecular weight of the vaccine particles, immunogens could only be physically characterized as a fraction in the void volume of Sepharose gel filtration. In search of better analytical methods, a computer-assisted electrophoretic technique for analyzing such vaccines was developed in the period from 1983 to 1995. This new approach made it possible to analyze highly negatively charged particles as large as or larger than intact viruses. 2-D gel patterns were generated that varied depending on the conditions of the particular vaccine preparation and were therefore characteristic of each vaccine sample. Thus, vaccine particle populations with a continuous size variation over a wide range (polydisperse) could be characterized according to size and free mobility (related to particle surface net charge density). These advances are reviewed in this article, since the developed methods are still a promising tool for vaccine quality control and for predicting immunogen effectiveness in the production of vaccines. The technique is potentially beneficial for Hib immunogens and other high-molecular-mass vaccines. Additional biomedical applications for this nondenaturing electrophoretic technique are briefly discussed and detailed information about computational and mathematical procedures and theoretical aspects is provided in the Appendices. [source] Synthesis of an oligosaccharide,polylysine dendrimer with reducing sugar terminals leading to acquired immunodeficiency syndrome vaccine preparationJOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 11 2005Huricha Baigude Abstract A novel cellobiose,polylysine dendrimer with reducing sugar terminals was synthesized in which the reactive reducing end of a disaccharide cellobiose was directing outward. Hexa- O -benzyl-4,-(1-carboxyethyl)-cellobioside (HBCEC) was synthesized through the reaction of a 4,-hydroxyl group of benzyl hexa- O -benzyl-cellobioside with methyl 2-chloropropionate, followed by the removal of the methyl ester group. HBCEC was reacted with polylysine dendrimer generation 3 (G3) to produce benzylated cellobiose,polylysine dendrimer G3. After debenzylation, a cellobiose,polylysine dendrimer G3 was obtained in which the reducing end of the cellobiose was the terminal group of the dendrimer. For the preparation of a dendrimer-type acquired immunodeficiency syndrome vaccine, the cellobiose,polylysine dendrimer was reacted with a tripeptide (glycyl,prolyl,leucine) and a cyclic oligopeptide from the human immunodeficiency virus by reductive amination; this produced a tripeptide-bound cellobiose,polylysine dendrimer and an insoluble compound, respectively. The structure analysis was carried out with NMR and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 2195,2206, 2005 [source] Immunogenicity of CIGB-230, a therapeutic DNA vaccine preparation, in HCV-chronically infected individuals in a Phase I clinical trialJOURNAL OF VIRAL HEPATITIS, Issue 3 2009L. Alvarez-Lajonchere Summary., Hepatitis C virus (HCV) is a worldwide health problem. No vaccine is available against this pathogen and therapeutic treatments currently in use are of limited efficacy. In the present study, the immunogenicity of the therapeutic vaccine candidate CIGB-230, based on the mixture of pIDKE2, a plasmid expressing HCV structural antigens, with a recombinant HCV core protein, Co.120, was evaluated. CIGB-230 was administered by intramuscular injection on weeks 0, 4, 8, 12, 16 and 20 to 15 HCV-chronically infected individuals, non-responders to previous treatment with interferon (IFN) plus ribavirin. Interestingly, following the final immunization, neutralizing antibody responses against heterologous viral pseudoparticles were modified in eight individuals, including six de novo responders. In addition, 73% of vaccinees exhibited specific T cell proliferative response and T cell IFN-gamma secretory response 24 weeks after primary immunization with CIGB-230. Furthermore, 33.3% of individuals developed de novo cellular immune response against HCV core and the number of patients (46.7% at the end of treatment) with cellular immune response against more than one HCV structural antigen increased during vaccination (P = 0.046). In addition, despite persistent detection of HCV RNA, more than 40% percent of vaccinated individuals improved or stabilized liver histology, particularly reducing fibrosis, which correlated with cellular immune response against more than one HCV antigen (P = 0.0053). In conclusion, CIGB-230 is a promising candidate for effective therapeutic interventions based on its ability for enhancing the immune response in HCV chronically infected individuals. [source] Computer-assisted 2-D agarose electrophoresis of Haemophilus influenzae type B meningitis vaccines and analysis of polydisperse particle populations in the size range of viruses: A reviewELECTROPHORESIS, Issue 4 2007Dietmar Tietz Dr. Abstract When protein,polysaccharide conjugated vaccines were first developed for the immunization of small children against meningitis caused by infection with Haemophilus influenzae type b (Hib), the vaccine preparations varied in immunogenicity. Testing for immunogenicity was time-consuming and alternative analytical procedures for determining vaccine quality were unsatisfactory. For example, due to the very high molecular weight of the vaccine particles, immunogens could only be physically characterized as a fraction in the void volume of Sepharose gel filtration. In search of better analytical methods, a computer-assisted electrophoretic technique for analyzing such vaccines was developed in the period from 1983 to 1995. This new approach made it possible to analyze highly negatively charged particles as large as or larger than intact viruses. 2-D gel patterns were generated that varied depending on the conditions of the particular vaccine preparation and were therefore characteristic of each vaccine sample. Thus, vaccine particle populations with a continuous size variation over a wide range (polydisperse) could be characterized according to size and free mobility (related to particle surface net charge density). These advances are reviewed in this article, since the developed methods are still a promising tool for vaccine quality control and for predicting immunogen effectiveness in the production of vaccines. The technique is potentially beneficial for Hib immunogens and other high-molecular-mass vaccines. Additional biomedical applications for this nondenaturing electrophoretic technique are briefly discussed and detailed information about computational and mathematical procedures and theoretical aspects is provided in the Appendices. [source] Mass spectrometry analysis of the influenza virus,MASS SPECTROMETRY REVIEWS, Issue 1 2009Kevin M. Downard Abstract The role of mass spectrometry to probe characteristics of the influenza virus, and vaccine and antiviral drugs that target the virus, are reviewed. Genetic and proteomic approaches have been applied which incorporate high resolution mass spectrometry and mass mapping to genotype the virus and establish its evolution in terms of the primary structure of the surface protein antigens. A mass spectrometric immunoassay has been developed and applied to assess the structure and antigenicity of the virus in terms of the hemagglutinin antigen. The quantitation of the hemagglutinin antigen in vaccine preparations has also been conducted that is of importance to their efficacy. Finally, the characterization and quantitation of antiviral drugs against the virus, and their metabolites, have been monitored in blood, serum, and urine. The combined approaches demonstrate the strengths of modern mass spectrometric methods for the characterization of this killer virus. © 2008 Wiley Periodicals, Inc., Mass Spec Rev 28:35,49, 2009 [This article was published online 10 September 2008. An error was subsequently identified. This notice is included in the online and print versions to indicate that both have been corrected 7 November 2008.] [source] | ||||||||||