Humoral responses in mice following vaccination with DNA encoding glutathione S-transferase of Fasciola hepatica: effects of mode of vaccination and the cellular compartment of antigen expression

The humoral responses in mice following vaccination with DNA constructs enc oding Fasciola hepatica glutathione S-transferase (GST) have been evaluated GST47 cDNA was subcloned into two DNA vaccine vectors, VR1012 and VR1020, which direct expression to the cytoplasmic and extracellular compartments, respectively. Expression was confirmed by transfection into COS 7 cells. Gr oups of mice were vaccinated with these constructs, by either intramuscular injection with the VR1012-or VR1020-based constructs, or intradermal vacci nation (with a gene gun) with the VR1020-based construct. Vaccination with the construct designed for secretion resulted in an increased humoral respo nse compared to vaccination with the nonsecretory construct. The level of t he total humoral response after vaccination with the secretion construct wa s not dependent on the route of vaccination. However, the isotype profile o f the response differed between the groups; intramuscular vaccination with the construct directing cytoplasmic expression yielded an immunoglobulin (I g)G(2a) dominant (Th1-type) response, intradermal vaccination with the secr etory construct a IgG(1)/IgE dominant (Th2-type) response, and intramuscula r vaccination with the secretory construct a mixed isotype response. These results demonstrate that the immunogenicity of a DNA vaccine based on Fasci ola GST, as well as the isotype of the response against GST, is determined by the mode of vaccine administration.