Biomedical Engineering Reference
In-Depth Information
14.2 DNAVaccines
14.2.1 The Birth of DNA Vaccination
In. the. early. 1990s,. reports. from. a. number. of. different. groups. paved. the. foundation. for.
DNA. vaccines.. Stephen. Johnston. and. colleagues. described. the. ability. of. DNA. expres-
sion.plasmids.coated.onto.gold.beads.and.delivered.into.mice.to.drive.the.expression.of.
a. foreign. protein. and. stimulate. an. antibody. response.
7
. Concurrently,. Margaret. Liu. and.
colleagues. reported. on. the. induction. of. antibodies. and. cellular. immune. responses. to.
inluenza. A. in. mice
8
;. Harriet. Robinson. and. her. group. demonstrated. protection. of. mice.
from.inluenza.by.delivering.inluenza.DNA
9
;.and.David.Weiner.and.colleagues.reported.
that.intramuscular.injection.of.HIV.antigen-encoding.plasmids.induced.antigen-speciic.
cellular.and.humoral.immune.responses.
10
.Although.a.number.of.previous.reports.dem-
onstrated.the.ability.of.DNA.plasmids.to.be.transfected.in.vivo
,
these.reports.were.the.irst.
to.demonstrate.an.immunological.consequence,.and.have.become.the.foundation.for.the.
ield.of.DNA.vaccines,.which.stimulate.pathogen-speciic.immune.responses.by.using.the.
host's.cells.to.express.the.antigen.(see.Chattergoon.et.al.
11
.for.more.details).
14.2.2 Differences between Traditional Vaccines and DNA Vaccines
There.are.several.advantages.with.DNA.vaccines.when.compared.to.the.aforementioned.
traditional. vaccines.. Since. DNA. vaccines. are. simply. expression. plasmids. that. encode.
speciic.antigens,.there.are.no.fears.of.infection.from.the.vaccine..Gene.expression.from.
these. plasmids. is. typically. driven. by. the. cytomegalovirus. (CMV). immediate. promoter,.
and. the. plasmid. includes. other. elements,. such. as. the. transcription. termination. signal.
and. a. prokaryotic. antibiotic. resistance. gene.
4
. Moreover,. safety. studies. in. humans. sug-
gest.minimal.evidence.for.plasmid.integration.into.the.host's.genome,.and.almost.all.of.
the.plasmids.are.cleared.from.the.body,.with.only.a.small.amount.remaining.at.the.site.
of injection..Over.a.2-month.experiment.conducted.by.Sheets.et.al.,.only.a.small.number.of.
the.immunized.animals.retained.the.plasmids.at.the.site.of.injection.(10%-20%),.with.only.
about.~100.copies.of.plasmid.per.site.
12
.In.addition,.there.is.limited.concern.for.biodistribu-
tion,.as.nontransfected.plasmids.are.rapidly.degraded.by.highly.active.nucleases,.reduc-
ing.agents,.and.charged.molecules.in.the.blood;.in.fact,.the.half-life.of.DNA.plasmids.in.
blood.is.approximately.2-3.minutes.
13
.Therefore,.DNA.vaccines.provide.minimal.toxicity.
because.the.excess.DNA,.or.nontransfected.DNA,.is.degraded.and.eliminated.rapidly.
A.distinction.between.DNA.vaccines.and.killed/subunit.vaccines,.which.are.also.non-
infectious,.is.that.DNA.vaccines.can.mimic.the.immunological.effects.of.attenuated.vac-
cines.. Since. DNA. vaccines. directly. transfect. the. host's. cells,. gene. expression. occurs. by.
using. the. host's. machinery—transcription. factors,. ribosomes,. mRNP,. etc.—allowing. for.
antigen. presentation. through. both. the. MHC. class. I. and. II. pathways.
4
. As. a. result,. DNA.
vaccines. induce. both. antigen-speciic. antibodies. and. T. cells,. unlike. killed/subunit. vac-
cines..Consequently,.DNA.vaccines,.like.attenuated.vaccines,.are.not.limited.by.the.type.
of.immune.response.needed.for.the.host.to.clear.infection..For.example,.subunit.vaccines.
rarely.generate.suficient.cellular.immune.response.required.for.clearing.viral.infections.
such.as.HCV.and.HPV..This.is.one.likely.reason.why.HPV.preventative.vaccines,.Gardasil
®
.
(Merck. &. Co.). and. Cervarix
®
. (GlaxoSmithKline),. fail. to. clear. preexisting. infections,. as.
these.vaccines.work.primarily.through.generating.antibodies.(see.Figure 14.1.for.mecha-
nism;.see.Table 14.2.for.differences.between.vaccines).
