Biomedical Engineering Reference
In-Depth Information
DNA + EP
DNA Alone
Control
0
500
1000
1500
2000
2500
Spot Forming Units per 10 6 PBMCs
(a)
I.D.
(+) EP
I.M.
I.D.
*
(-) EP
I.M.
*
0
2000
4000
Gag Endpoint Titer
(Serum antibody ELISA)
(b)
6000
8000
10000
FIGURE 14.3
Electroporation.of.DNA.vaccines.increases.both.cellular.and.humoral.immune.responses..(a).Cellular.immune.
response.(IFN-γ.spot-forming.units).was.measured.from.macaque.peripheral.blood.mononuclear.(PBMCs).after.
the.second.immunization..Rhesus.macaques.were.immunized.with.1.0.mg.of.DNA.encoding.the.HIV.Gag.and.
Env.antigens..The.cellular.responses.were.measured.via.stimulation.with.anti-Gag.and.anti-Env.peptides.over-
night.using.a.standardized.ELISpot.assay..(b).Serum.antibody.responses.in.rhesus.macaques.with.or.without.
electroporation.delivered.via.the.intramuscular.or.intradermal.route..Shown.is.the.response.after.two.immu-
nizations..*,.≤50.
14.3.4 Clinical Trials with DNA Vaccines Delivered with Electroporation
There. have. been. several. DNA. vaccine/electroporation. studies. in. the. clinic. evaluating. its.
eficacy.against.a.variety.of.diseases,.including.HIV,.HCV,.HPV,.and.cancer,.and.probably.a.
number.more.will.enter.the.clinic.in.the.next.few.years.(see.Table 14.3). A.number.of.factors.
have.been.evaluated.in.these.studies,.most.notably.safety,.tolerability.of.electroporation,.and.
induction.of.immune.responses..Thus.far,.no.adverse.reports.with.either.DNA.vaccination.
or.electroporation.have.been.reported,.including.anti-DNA.immune.responses.and.plasmid.
integration. 15,16,35 .However,.the.primary.limitation.with.previous.DNA.vaccine.trials.has.not.
been.issues.with.safety,.but.rather.with.immunogenicity.and.eficacy..Can.DNA.vaccines,.
especially.in.combination.with.electroporation,.induce.suficient.immune.responses.to.allow.
the. host. to. ight. infections. effectively. by. eliminating. preexisting. infections. or. preventing.
new. infections?. Clearly,. previous. clinical. studies. with. DNA. immunization. alone. suggest.
otherwise,.but.can.the.increased.effect.with.electroporation.overcome.this.hurdle?
To. begin. to. answer. this. question,. several. research. groups. are. now. investigating. elec-
troporation-delivered.DNA.vaccines.in.humans..Inovio.Pharmaceuticals.has.designed.a.
therapeutic.DNA.vaccine.against.cervical.cancer,.which.is.the.second.most.common.can-
cer.among.women.worldwide.and.the.most.common.cancer.in.developing.countries. 36 .The.
 
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