Biological features of genetic immunization

Abstract

Genetic immunization (a.k.a. DNA-based immunization) shows promise at least as a convenient method to test and discover new vaccines and may be an efficient vaccine delivery system. However, relatively little is known about the parameters affecting its effectiveness, let alone its basic underlying biological mechanisms. Here we report on investigations of some of the factors that determine the quantity and quality of the immune response with genetic immunization. We find that for non-toxic proteins the antibody response correlates well with the level of expression as does the cellular response to a certain level. The augmentation of the immune response by co-introduction of a cytokine gene as a genetic adjuvant is also responsive to the expression level of the antigen. The immune response is inversely correlated to the age of the mice and at least part of this effect is through level of expression of the antigen. Gene gun administration of the transgene to the skin has the advantage over muscle injection in that ca 100-fold less DNA is required for the same level of expression and the injections are more reproducible in effect. Finally, the apparent differences in Th2 (gun) vs Th1 (muscle) responses between the two modes can at least partly be accounted for by differences in the amount of plasmid DNA typically administered.