Biology Reference
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increase its cellular uptake, or to enable it to withstand extracellular
degradation for longer. Encapsulating the DNA into 29 or adhering the
DNA onto 30 microparticles likewise appears to increase the potency
of DNA vaccines by either protecting the DNA from degradation or
increasing its uptake by antigen processing cells, or both. Variants of
DNA have been incorporated into the sequences, such as the nt
sequence for anticipated drug mutations. 31
Genes encoding immune-stimulating molecules such as cytokines
have been added to the plasmids, in essence adding adjuvants to the
genes encoded by the DNA. 32 As noted above, the bacterial origin of
the plasmids means that the sequence and hence the methylation pat-
tern of the DNA enables it to activate Toll-like receptors, potentially
engaging the innate immune system in the process of stimulating cog-
nate immunity. 33
Different delivery devices or routes have also been employed in
efforts to increase the potency of the DNA vaccines, to stimulate spe-
cific types of immunity (such as mucosal immune responses), or to facil-
itate delivery for patient compliance or for resource-poor settings. The
initial demonstration of a DNA vaccine that could stimulate antibody
responses employed a “gene gun” to shoot DNA-coated gold beads
into the skin. 34 Such “particle-mediated” injection has been used in
clinical trials to generate antibodies against Hepatitis B surface antigen 35
using DNA encoding the antigen. Although the DNA immunizations
resulted in lower titers and utilized more immunizations that with the
licensed protein vaccine, they still showed the ability of DNA immu-
nized via the gold beads to clinically produce the desired immune
response. In a further study, patients who had not responded well to the
licensed (recombinant protein) hepatitis vaccine made antibodies fol-
lowing immunization with the DNA vaccine 36 given by gene gun.
DNA transfer by apoptotic cells appears to induce a receptor-
independent immune response. The DNA, present in the apoptotic
bodies from transfection by plasmids or by the infectious agent, is
taken up by antigen presenting cells and appears to induce good
immune responses. 37
Devices other than traditional syringes are being tested to directly
propel the DNA vaccine into the skin (for example, the Biojector) 3,38
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