Biology Reference
In-Depth Information
Additional studies in a variety of pre-clinical models of various dis-
eases rapidly demonstrated the broad applicability of the DNA vaccine
technology. Perhaps just as importantly, the ease with which the vari-
ous laboratories used off-the-shelf plasmids and bacterial lines for
production of the DNA vaccines demonstrated the robustness of the
technology. The models in which DNA vaccines were utilized for
inducing immune responses or pre-clinical efficacy included a variety
of infectious diseases caused by viruses, bacteria and parasites. Other
types of disease such as cancer, autoimmune diseases and allergy
9,10
were also shown to be amenable to DNA vaccine prophylaxis or ther-
apy in pre-clinical models. The applications for allergies (asthma)
11
and
autoimmune diseases (such as diabetes)
12
are based upon the ability of
the DNA to not simply generate cellular immunity, but to alter the
type of T cell helper response for the particular protein antigen. This
shift in the Th1 and Th2 responses and other data demonstrate that
the role of the DNA is not simply to function as a carrier of the gene
encoding the antigen, but that the DNA itself also has immune effects
and/or that the method of generation of the immune response is
different from the means by which the abnormal autoimmune aller-
gic response against a given antigen occur.
A number of applications have moved the field forward regarding
the influence on allergic diseases, autoimmune diseases and cancer. One
of the most interesting properties of a DNA vaccine, is its ability to not
only induce Th1 responses, but to also divert the immune response
away from antibody production. Thus, allergic responses by IgE have
been redirected by small doses of DNA encoding endogenous enzymes,
such as the beta-galactosidase. The anti-allergic properties of the DNA
plasmid were attributed both to an induction of Th1 response, as well
as a non-induction of IgE antibodies, which induce allergy in this
preclinical mouse model.
13
The balance between allergic disease and
autoimmunity is fine, however, and in some diseases an autoimmune
reactivity is instead desirable. This approach involves the induction by
DNA of immune responses against slightly heterologous substances.
Studies have addressed the means by which the DNA is able to
generate cytolytic T cell responses despite the concern that protein
