Page 794 - Veterinary Immunology, 10th Edition
P. 794

Polynucleotide vaccines must get inside target cells. This can be
  VetBooks.ir  done by intramuscular injection or by “shooting” the DNA

               plasmids directly through the skin adsorbed onto microscopic gold
               beads fired by a “gene gun.” Although intramuscular injection is

               very inefficient because the transfection rate is low (about 1% to 5%
               of myofibrils in the vicinity of an intramuscular injection site), the
               expression can persist for at least 2 months. The gene products are
               either treated as endogenous antigens and displayed on the cell

               surface or secreted and presented to antigen-processing cells. This
               processed antigen thus preferentially stimulates a Th1 response
               associated with IFN-γ production. The use of a gene gun is more
               efficient than injection since some of this DNA is taken up by

               dendritic cells, and it minimizes degradation. By bypassing TLR9,
               the DNA preferentially stimulates a Th2 response. Viral DNA in
               eye drops can induce an IgA response in the tears and bile of
               recipients.

                  Immunization with purified DNA allows viral antigens to be
               presented in their native form. They are synthesized in the same
               way as antigens during a viral infection. This is more effective than
               the use of recombinant proteins since it has proved difficult to

               create the proteins in the correct conformation in microbial systems.
               It is also possible to select only the genes for the antigen of interest
               rather than using a complex carrier organism with its own large
               gene pool and antigenic mass.



               Prime-Boost Strategies

               It has long been normal practice to use exactly the same vaccine for
               boosting an immune response as was employed when first priming
               an animal. This approach has many advantages, not the least of

               which is simplicity in manufacturing and regulating vaccine
               production. There is, however, no reason why different forms of a
               vaccine should not be used for priming and for boosting. This
               approach is known as a prime-boost strategy. Under some
               circumstances this may result in significantly improved vaccine

               effectiveness. The prime-boost approach is somewhat empirical,
               and researchers may simply test numerous vaccine combinations to
               determine which combination yields the best results. Prime-

               boosting has been most widely investigated in attempts to improve




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