Pharmacogenomics in the preclinical development of vaccines: evaluation of efficacy and systemic toxicity in the mouse using array technology.
The development of vaccines, conventional protein based as well as nucleic acid based vaccines, and their delivery systems has been largely empirical and ineffective. This is partly due to a lack of methodology, since traditionally only a few markers are studied. By introducing gene expression analysis and bioinformatics into the design of vaccines and their delivery systems, vaccine development can be improved and accelerated considerably. Each vaccine antigen and delivery system combination is characterized by a unique genomic profile, a "fingerprint" that will give information of not only immunological and toxicological responses but also other related cellular responses e.g. cell cycle, apoptosis and carcinogenic effects. The resulting unique genomic fingerprint facilitates the establishment of molecular structure--pharmacological activity relationships and therefore leads to optimization of vaccine development.
Regnström
Karin J
KJ
School of Pharmacy, University of Connecticut, Storrs, Connecticut, USA.
D000818:Animals; D002478:Cells, Cultured; D016000:Cluster Analysis; D019295:Computational Biology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000276:immunology; D053263:Gene Regulatory Networks; D023281:Genomics; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D020411:Oligonucleotide Array Sequence Analysis; D010597:Pharmacogenetics; D013329:Structure-Activity Relationship; D014612:Vaccines / Q000494:pharmacology* / Q000633:toxicity
D016207:Cytokines; D014612:Vaccines