Nucleic Acid Vaccination

Doolan, D.L., and S.L. Hoffman, Nucleic acid vaccines against malaria. Chem Immunol, 2002. 80 308-21. 

Nucleic acid vaccination Rothel ef al. (1997b), Drew etal. (1999, 2000a, b, 2001 a,b) Scheerlinck etal. (2001)... 

Rothel, J.S., Waterkeyn, J.G., Strugnell, R.A., Wood, P.R., Seow, H.F., Vadolas, J. and Lightowlers, M.W. (1 997b) Nucleic acid vaccination of sheep use in combination with a conventional adjuvanted vaccine against Taenia ovis. Immunology and Cell Biology 75, 41 16. 

Cook, R.M., Carvalho-Queiroz, C., Wilding, G. and LoVerde, P.T. (2004) Nucleic acid vaccination with Schistosoma mansoni antioxidant enzyme cytosolic superoxide dismutase and the structural protein filamin confer protection against the adult worm stage. Infection and Immunity 72, 61 12-6124. 

Skin is rich in dendritic cells, which are potent initiators of immune responses and possess the co-stimulatoiy and adhesion molecules required for T cell activation. In addition, dendritic cells possess a unique ability to process and present extracellular antigens in the context of both class I and class II molecules. Thus, transfection of plasmids into these cells is likely to elicit both cellular and humoral responses. Specific targeting of dendritic cells residing in the lymph nodes will likely represent an attractive strategy for providing a robust immune response with nucleic acid vaccines. 

Xiang ZQ, Spitalnik SL, Cheng J, Erikson J, Wojczyk B, Ertl HC. Immune responses to nucleic acid vaccines to rabies virus. Virology 1995 209 569-79. 

Preclinical Results and Clinical Applications. Both pDNA- and mRNA-based vaccinations were demonstrated to be efflcacious in animal models as prophylactic or therapeutic immunotherapies against tumors, infectious diseases, and allergy. Two pDNA-based vaccines are commercialized for veterinary use an anti-equine fever and an anti-infectious hematopoietic necrosis virus (IHNV) for farm-raised salmons. In humans, several formulations of nucleic acid vaccines are tested in clinical trials (see the actualized list of trials at www.clinicaltrials.gov). Although pDNA-based vaccine trials were reported in the context of antitumor, antivirus (HIV, influenza virus, HBV) and antiparasite Plasmodium falciparum) approaches, mRNA-based vaccines were up to now tested only as immunotherapies against cancer (review by Liu and Ulmer for pDNA [35] and Pascolo for mRNA [36]). 

Standardization and Testing". The Center for Biologies Evaluation and Research has set guidelines for the vaccine which include standards for si2e of the individual polysaccharides and specifications for both purity (absence of protein and nucleic acid) and chemical and immunological identity. 

In current practice the fluorescence assay is often followed by the use of hybridization techniques when more selectivity is required. We have for instance used the fluorescence techniques to obtain data on the nucleic acid content of malaria vaccine proteins produced in Escherichia coli. The rapid turnaround time of the fluorescence assay is particularly useful during the early stages of purification to determine the optimal process conditions. After the final process has been arrived at and a variety of methods used to assess the nucleic acid content (including the hybridization techniques), the fluorescence method can be developed for routine quality-control purposes. In certain cases, particularly at high protein concentrations, the dye may bind to the protein with... 

Peptoids have also shown great utility in their ability to complex with and deliver nucleic acids to cells, a critical step toward the development of antisense drugs, DNA vaccines, or gene-based therapeutics. Most non-viral nucleic acid delivery systems are based on cationic molecules that can form complexes with the polyan-... 

Heat is the most reliable method of virus disinfection. Most human pathogenic viruses are inactivated following exposure at 60°C for 30 minutes. The virus of serum hepatitis can, however, survive this temperature for up to 4 hours. Viruses are stable at low temperatures and are routinely stored at -40 to -70°C. Some viruses are rapidly inactivated by drying, others survive well in a desiccated state. Ultraviolet light inactivates viruses by damaging their nucleic acid and has been used to prepare viral vaccines. These facts must be taken into account in the storage and preparation of viral vaccines (Chapter 15). 

This chapter will describe the potential of carbon nanotubes in biomedicine. It will illustrate the methodologies to render nanotubes biocompatible, the studies on their cell uptake, their application in vaccine delivery, their interaction with nucleic acids and their impact on health. 

DNA vaccines Direct injection of nucleic acid contents HIV, malaria, influenza, hepatitis B virus, cancer... 

The use of needle-free jet devices for the delivery of nucleic acids has been described for various disease models, and has been found to generally enhance DNA uptake in various tissues and to increase DNA vaccine efficacy. Jet injection has been found to be an efficient method to induce papillomas in rabbits by inoculation with cottontail rabbit papillomavirus DNA (Brandsma et al., 1991). Jet injection has been used to introduce DNA through the skin surface, effectively transfecting skin, muscle, fat and mammary tumor tissue (Furth et al., 1992). 

Peptide-based gene delivery, 334 Peptide nucleic acid (PNA), 73,252 Pharmacokinetics, 409 Polyethyleneimine (PEI), 369 Peptides with thiol groups, 348 Persistence of gene expression, 10,463 Physiological Pharmacokinetics, 423 PNA binding affinity, 75 Poly anion interchange, 179 Poly cations, 164 Polymeric gel, 447 Polyamidoamine (PAMAM), 376 Polyaminomethacrylates, 379 Poly(L-lysine), 336, 369 Poly(vinyl pyrrolidone) (PVP), 382 Prophylactic vaccines, 474... 

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