Biomedical Engineering Reference
In-Depth Information
CD8+
T cell
MHC I
CD28
DNA
injection
B7
1 Cytokines
CD4+
T cell
CD8 & CD3
Cytokine receptors
Secreted
proteins
APCs
CD28
Electroporation
B7
Muscle
cell
MHC II
CD4 &
CD3
2 cytokines
B cell
Cytokine receptors
FIGURE 14.1
DNA. vaccines. activate. both. Th1. and. Th2. immune. responses.. Injection. of. DNA. and. subsequent. electropora-
tion.increases.plasmid.transfection.into.muscle.cells..The.plasmids,.which.express.an.antigen.of.interest,.are.
expressed. in. the. host's. muscle. cells,. and. the. antigen. peptides. are. presented. via. MHC. class. I. presentation,.
leading.to.CD8
+
.T.cell.activation..The.antigens.can.also.be.secreted.by.the.muscle.cells.and.taken.up.by.antigen-
presenting.cells,.leading.to.MHC.class.II.presentation.and.CD4
+
.T.cell.activation..In.addition,.coexpression.of.
cytokine.plasmids.can.drive.Th1.or.Th2.immune.responses.
Another.advantage.with.DNA.vaccines.is.that.they.allow.for.the.engineering.of.immune.
responses.with.adjuvants..By.simply.coimmunizing.the.DNA.vaccine.with.plasmids.that.
encode. certain. cytokines,. one. can. skew. the. vaccine-induced. response. by. altering. the.
microenvironment.of.antigen.presentation..For.example,.coexpressing.Th1-driving.cytok-
ines. such. as. interleuken. (IL)-12. plasmids. dramatically. increases. the. magnitude. of. the.
antigen-speciic. T. cell. response.. As. shown. in. Figure 14.1,. coexpression. of. cytokines. can.
TABLE 14.2
Comparison.of.Live.Attenuated,.Subunit/Killed,.and.DNA.Vaccines
LiveAttenuated
Subunit/Killed
DNA
Humoral.response
Yes
Yes
Yes
Cellular.response
Yes
Minimal.to.none
Yes
Antigen.presentation
Class.I.and.II
Class.II
Class.I.and.II
Safety.(potential.
infection?)
Yes
No,.but.inactivation.must.
be.complete
No
Production.(cost.and.
ease?)
Expensive.and.dificult.
(virus.must.be.attenuated)
Easier.to.develop.than.live.
attenuated.(protein,.thus.
strict.storage.conditions)
Relatively.inexpensive.
and.easy.to.manufacture.
(DNA.is.stable)
