Immunogenicity chemicals

Albumin is an attractive macromolecular species to prepare pharmaceutical carriers used for the sustained delivery of therapeutic agents since this protein is biodegradable, bio-compatible, non-toxic, and non-immunogenic. Chemical groups susceptible to radical pol5mierization were introduced onto... 

Development of conjugate and peptide vaccines requires the typical organic synthesis process and purification. This is a new area for vaccine technologists. Again, the main concern is to maintain the immunogenicity of the vaccine candidate during the chemical reaction and purification steps. 

E. C. (1988b). Incorporation of the major outer membrane protein of Neisseria gonorrhoeae in saponin-Upid complexes (Iscoms) Chemical analysis, some structural features, and comparison of their immunogenicity with three other antigen delivery systems, Inf. Immun., 56, 432-438. 

The chemical adducts formed by reaction of aldehydes with lysine residues form highly immunogenic epitopes, and antibodies have been prepared specific for malondialdehyde- and 4-hydroxynonenal-conjugated LDL (Gonen et al., 1987 Yla-Herttuala et al., 1989 Jurgens et al., 1990). These antibodies cross-react with material in atherosclerotic lesions but not normal tissue, thus supporting the central role of lipid peroxidation in the patho nesis of atherosclerosis (Yla-Herttuala et al., 1989, 1991). 

Aptamers appear to display low immunogenicity but, when administered systemically, they are quickly excreted via size-mediated renal clearance. In order to prevent renal removal, such aptamers are usually conjugated to PEG. PEG may also help further protect the aptamers from degradation by serum nucleases native aptamers are prone to nuclease attack, but their half-lives can most effectively be extended via chemical modification, as discussed earlier in the context of antisense agents. 

A most important technique which has been developed as an extension of the isotope dilution principle is that of radioimmunoassay (RIA). Analyses by this method employ substoichiometric amounts of specific binding immuno-chemical reagents for the determination of a wide range of materials (immunogens) which can be made to produce immunological responses in animals such as sheep or rabbits. It is possible to combine the specificity of an immunochemical reaction with the extreme sensitivity of radiotracer detection. Analytical methods based upon these principles have achieved wide applicability in the determination of organic compounds at trace levels. 

Immunodeficiency has been associated with an increased incidence of viral-induced cancers, which tend to be more immunogenic than those that are chemically-induced. Cancers related to immunosuppression include leukemia and cancers of the skin (seen in transplant patients4) as well as Kaposi s sarcoma and EB V-associated B cell lymphomas (observed in HIV/AIDS patients). 

Some xenobiotics may have divergent mechanisms of autoimmune responses. For example, hydralazine demonstrates adduct reactivity as well as inhibition of DNA methylation [68,73], while procainamide inhibits DNA methylation, forms immunogenic NPA, and disrupts clonal selection in the thymus [68, 72, 74], It is this complicated pattern of effects that makes assessment of autoimmune potential in the laboratory for new xenobiotics almost impossible. Animal models can sometimes be recreated to resemble human disease [74], and thus may be useful for therapy considerations, but are difficult to utilize for screening chemicals for hazard potential due to the diverse nature of autoimmunity mechanisms and physiological presentation. While evidence supports many different mechanisms for xenobiotic-induced autoimmune reactions, none have conclusively demonstrated the critical events necessary to lead to the development of autoimmune disease. Therefore, it is difficult to predict or identify xenobiotics that might possess the potential to elicit autoimmune disorders. 

Fig. 5 Chemical structure of the hapten conjugated to BSA used as immunogen by Roberts et al. [158] and Meyer et al. [154] to raise antibodies against dexamethasone. Structures of other corticosteroids subsequently tested by Creaser et al. [180] in order to evaluate the selectivity of the ELISA obtained are also shown...

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