Applications of Gene Therapy - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 275

vaccines represent a new approach for immunization and immunotherapy in which
DNA containing the genes that encode proteins of the pathogen are delivered in a
subject, rather than a live or inactivated organism. These vaccines utilize the prin-
ciples and advancements in immunology and molecular biology to modulate immune
responses (cellular, humoral, or both) against selected antigens.
DNA vaccines offer many advantages over conventional vaccines and are aimed
to elicit immunity against diseases for which traditional vaccines and treatments have
not worked, improve vaccines, and treat chronic diseases [15] . The various features
of DNA vaccines could be summarized as follows:
1. They produce antigenic protein to be recognized by B-cells and presentation by major his-
tocompatibility complex (MHC) class I and II molecules to prime helper T-cells and cyto-
toxic T lymphocytes (CTL).
2. They elicit both humoral and cellular immunity.
3. A single immunization can express multiple antigens.
4. They can be efficiently manufactured and well characterized.
5. They are well tolerated and safe.
6. Genetic vaccines are better suited for long-term expressions and cheaper to prepare than
protein-based vaccines.
6.2.1 Mechanism of Induction of Cellular and Humoral Immune
Response
In the human body, the cellular immune response is provided by CD4 and CD8
T-cells. Any exogenous antigen (killed pathogens or proteins derived from live vac-
cines) in the body is taken up by antigen-presenting cells (APCs) through phagocyto-
sis or endocytosis. This foreign antigen is processed and presented by MHC class II
or I molecules to stimulate CD4 and CD8 T-cells. The activation of CTL (CD8
T-cells) produces an immune response against the pathogens. In contrast, the activa-
tion of Th1-type CD4 T-cells produces interferons (IFN-) and interleukins (ILs)
such as IL-2 and IL-12, and promotes cell-mediated immunity. However, the activa-
tion of Th2 type CD4 T-cells produces IL-4, IL-5, IL-10, and IL-13, and provides
help for B-cell differentiation and humoral immunity [16] .
In DNA vaccines ( Fig. 6.4 ), the delivered DNA either alone or with the vector,
expresses itself in the nucleus of APCs to produce the “naive” form antigenic protein
that undergoes posttranslational modifications and is presented by MHC class II and I
to produce the immune response against the targeted antigen. The generation of T-cell
(T helper cells and CTLs) responses by DNA vaccines is identified as a promising
strategy to act against intracellular bacteria and parasites, as well as viral infections
and cancer [17-20] . DNA vaccines are also shown to elicit humoral immune (antibod-
ies) response by stimulation of B-cells, which is enhanced by cytokines released from
activated T-cells. The antibody subtypes like immunoglobulin IgG, IgM, and IgA are
induced by DNA vaccination [21-23] . There are two ways to induce CTLs' medi-
ated immune responses. The first way is by direct delivery of DNA vaccine to APCs,
which process and present it to activate CTL. The alternative way is known as “cross
priming.”