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.

Pharmacogenomics in the evaluation of efficacy and adverse events during clinical development of vaccines.

The understanding of vaccine-induced immune responses in adults and infants is limited. Current vaccination schedules for infants are frequently debated. Especially, the relationship among the timing, the frequency of the dosing, and the generation of an immunological memory are debated. Vaccine antigen-induced cytokine responses to vaccinations given in infancy are of particular interest because little is known about cellular responses in this age, and the information available is based on antibody responses. Pharmacogenomics is ideally suited to study cellular responses related to immune response; in addition, toxicity, inflammation, apoptosis, stress, and oncogenesis can be monitored, since the expression of thousands of genes can be measured in a single experiment.