bun vaccin
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VACCINES
1. Introduction
2. The Immune System
3. Subunit & Peptide Vaccines
4. Attenuated Vaccines
5. Vector Vaccines
6. acteria! Anti"en de!i#ery
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Immunization$ a procedure desi"ned to increaseconcentrations o% antibodies andor e%%ector T'ce!!s (hich are reacti#e a"ainst in%ection )or
cancer*.
Immuni+ation procedure ca!!ed #accination and theimmuni+in" a"ent ca!!ed #accine )or ,serum- in
historica! re%erences*
VACCINES
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isco#ery o% Vaccination
isco#ered in 1/06 by
r. d(ard enner
Tested empirica! no(!ed"e$mi!d catt!e disease co(poprotects a"ainst dead!y humandisease sma!!po
scratchin" !iuid %rom co(posores into the boys sin '7 %u!!protection a"ainst sma!!po
VACCINES
Introduction
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VACCINES
The Immune system
Immune System
Innate
(Nonspecific)Adaptive
(Specific)
Protects/re-exposure
Cellular Components Humoral Components Cellular Components Humoral Components
Interactions between the two systems4
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Innate Immunity Adapti#e Immunity
Innate #ersus Adapti#e Immunity
8 9o memory
8 9o time !a"
8 9ot anti"en speci%ic
8 A !a" period
8 Anti"en speci%ic
8 e#e!opment o% memory
VACCINES
The Immune system
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VACCINES
The Immune system
First-line defense: physical and chemical barrierThe %irst'!ine de%ense inc!udes barriers to in%ection: such as sin and mucus coatin" o% the "ut and air(ays.
Second-line defense:Phaocytic cellspha"ocytic ce!!s );ye!oid ce!!s* )macropha"es and neutrophi! "ranu!ocytes* can destroy )pha"ocytose* %orei"n
substances. Pha"ocytosis in#o!#es di"estion o% the bacterium by usin" en+ymes.
Anti-microbial proteinsAnti'microbia! proteins are acti#ated i% a patho"en passes throu"h the barrier o%%ered by sin. There are se#era!c!asses o% antimicrobia! proteins: such as acute phase proteins )%or eamp!e: proteins that enhance pha"ocytosis*:!yso+yme: and the comp!ement system.
The comp!ement system is a #ery comp!e "roup o% serum proteins: (hich is acti#ated in a cascade %ashion. Threedi%%erent path(ays are in#o!#ed in comp!ement acti#ation$
A cascade o% protein acti#ity %o!!o(s comp!ement acti#ation '7 destruction o% the patho"en and in%!ammation
Inter%erons are a!so anti'microbia! proteins.'7 secreted by #irus'in%ected ce!!s '7 di%%use rapid!y to nei"hborin" ce!!s '7 inhibit the spread o% the #ira! in%ection.
Innate Immune System
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The adapti#e immune system: a!so ca!!edthe
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=e!!s o% the Immune System
Immune System
Myeloid Cells Lymphoid Cells
Granulocytic Monocytic T cells B cells
Neutrophils
Basophils
Eosinophils
Macrophages
Kupffer cells
Dendritic cells
elper cells
Suppressor cells
Cytoto!ic cells
"lasma cells
Natural Killer
cells
VACCINES
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e#e!opment o% the Immune System
VACCINES
myeloid
Granulocyte
lymphoid
nk
thymus
CD8+
CD4+
CTL
T2
T1
!onocyte
"#Cells $
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The Immune System
VACCINES
>hat ?appens durin" an in%ection@
Innate Immunity acti#ated
! macropha"es s!ip bet(een ce!!s etra#asationB to arri#e
! cytoine chemica!s attract other ,troops- chemotaisB
! histamine chemica!s di!ate b!ood #esse!s %or easier access to inCury#asodi!atationB
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The Immune System
VACCINES
;acropha"es )The ,bi" eaters-* Pha"ocytic ce!!s '
ab!e to in"est sma!! %orei"n in#aders! neutrophi!s! monocyte
they re!ease cytoines that enhance the immuneresponse
;ast ce!!s basophi!s
! re!ease histamine that di!ates b!ood #esse!s
! causes redness erythremaB: s(e!!in"edemaB: and heat %e#erB
=a!! %or he!p %rom the AAPTIV I;;D9 System'7 resu!ts in a coordinated success%u! de%ense E
;aCor p!ayers . . . the !ymphocytes
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The Immune System
VACCINES
The Adapti#e Immune system
1. ?umora! immune system$ '7 acts a"ainst bacteria and #iruses usin" immuno"!obu!ins)a!so no(n as antibodies* '7 produced by ce!!s.
2. =e!!u!ar immune system$ '7 destroys intrace!!u!ar patho"ens )such as #irus'in%ectedce!!s and mycobacteria F causin" tubercu!osis* usin" T ce!!s )a!so ca!!ed
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The Immune System
VACCINES
The Adapti#e Immune system
Acti#ated ce!!s di%%erentiate into . . .
! Antibody producin" ce!!s attac modeB
!;emory ce!!s remembers & %uture protectionB
Antigen & T-helper cell
memory
antibodies
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Princip!e o% Vaccination
VACCINES
A !accine renders the recipient resistant to infection.
urin" #accination a #accine is inCected or "i#en ora!!y.
The host produces antibodies %or a particu!ar patho"en.
Dpon %urther eposure the patho"en is inacti#ated by theantibodies and disease state pre#ented.
Henera!!y to produce a #accine the patho"en is "ro(n in cu!tureand inacti!ated or non!irulent%orms are used %or #accination.
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Immuni+ation$
>hen per%ormed be%ore eposure to an in%ectious a"ent )orsoon a%ter eposure in certain cases*: it is ca!!edimmunoprophyla"is:
intended topre!ent the in%ection.
>hen per%ormed durin" an acti#e in%ection )or eistin" cancer*:it is ca!!ed immunotherapy: intendin" to cure the in%ection )orcancer*
VACCINES
Princip!e o% Vaccination
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Types o% Immunity$
VACCINES
Princip!e o% Vaccination
'7 T(o mechanisms by (hich immuni+ation can be achie#ed
Passi!e immunization$
! Protecti#e Abs ''7 non immune recipient! 9o immuno!o"ica! memory
Acti!e immunization$! Induction o% adapti#e immune response: (ith protection and
memory.
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Passi#e #ersus acti#e immuni+ation$
VACCINES
Princip!e o% Vaccination
-# $%PE AC&'I(E) $*(+',* Passi!e Immunization '7 9atura! materna! serummi!
'7 Arti%icia! immune serum
-# $ype AC&'(IE) $*(+',* Acti!e Immunization '7 9atura! in%ection '7 Arti%icia! in%ection$
Attenuated or"anisms )!i#e* inacti#ated or"anisms )dead* =!oned "enes o% microbio!o"ica! anti"ens Puri%ied microbia! macromo!ecu!es Synthetic peptides 9A
IArti%icia! re%ers to steps in#o!#in" human inter#ention
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;echanism o% Vaccination$
VACCINES
Princip!e o% Vaccination
stab!ish resistance to #iruspatho!o"ica! or"anism by e#oin" animmune response
1. Hi#e host a %orei"n or"anismprotein in non'in%ectious %orm '7 acti#e
immuni+ation
2. Antibodies are "enerated Ab binds to sur%ace proteins o% or"anism'7 passi#e immuni+ation
Jther #accination components$8 Ad.u!ant: chemica!s in the #accine so!ution that enhance the immune response
F A!um F A" in the #accine c!umps (ith the a!um such that the A" is re!eased
F s!o(!y: !ie a time're!ease capsu!e
F "i#es more time %or memory ce!!s to %orm
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Princip!e o% Vaccination
VACCINES
$raditional Vaccines:
! Hro( in anima!s )#accinia inca!#es %or sma!!poG rabbit
brains %or rabies*
! Simp!e bacteria! cu!ture)=ho!era #ibrio* theninacti#ation
! Hro( in e""s )in%!uen+a:#accinia* then inacti#ate
'1%% million e((s used)or in)luen*a in the ,-
e.ery year 1$
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Princip!e o% Vaccination
VACCINES
Kimitations To Traditiona! Vaccines$
'7 canLt "ro( a!! or"anisms in cu!ture
'7 sa%ety to !ab personne!
'7 pense
'7 insu%%icient attentuation )!i#in" a"ent a!tered to becomeharm!ess or !ess #iru!ent*
'7 re#ersion to in%ectious state
'7 need re%ri"eration
'7 do not (or %or a!! in%ectious a"ents
'7 in%antschi!dren recei#e them F immature immunity 2%
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Princip!e o% Vaccination
VACCINES
9e( Heneration o% Vaccines$
(ecombinant )NA technoloy is bein" used to produce a ne("eneration o% #accines.
Virulence enes are deletedand or"anism is sti!! ab!e to stimu!atean immune response.
/i!e nonpathoenic strainscan carry anti"enic determinants %rompatho"enic strains.
I% the a"ent cannot be maintained in cu!ture: enes of proteins%or
anti"enic determinants can be c!oned and epressed in ana!ternati#e host e.". 1. co!i.
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Princip!e o% Vaccination
VACCINES
Mecombinant Vaccines$
1. Subunit Vaccinespeptide #accinesHenetic immuni+ation
2. Attenuated Vaccines
3. Vector Vaccines
4.acteria! Anti"en e!i#ery Systems'7 "hosts '7 de!i#ery systems )net semester*
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Princip!e o% Vaccination
VACCINES
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SubunitPeptide Vaccines
VACCINES
8o 9JT use entire #irus or bacteria )patho"enic a"ent*
8Dse components o% patho"enic or"anism instead o% (ho!e or"anism
8Ad#anta"e$ no etraneous patho"enic partic!es i.e. 9A
8isad#anta"e$ Is protein the same as in situ@ '7 =ost@
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SubunitPeptide Vaccines
VACCINES
It has been sho(ed that the capsid or en!elope proteinsare enou"h tocause an immune response$ ?erpes simp!e #irus en#e!op "!ycoprotein J.
Noot and mouth disease #irus capsid protein )VP1* trace!!u!ar proteins produced by ;ycobacterium tubercu!osis.
Subunit Vaccines Antibodies usua!!y bind to surface proteinso% the patho"en or proteins
"enerated a%ter the disruption o% the patho"en.
indin" o% antibodies to these proteins (i!! stimu!ate an immune response. There%ore proteins can be use to stimu!ate an immune response.
e#e!opment o% Subunit #accines based on the %o!!o(in" obser#ation$
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SubunitPeptide Vaccines
VACCINES
amp!e %or a subunit #accine '7 Tubercu!osis $uberculosisis caused by ;ycobacterium tubercu!osis. The bacterium %orms !essions in the tissues and or"ans '7 causin" ce!! death.
J%ten the !un" is a%%ected. About 0 billion people are infectedand there are 3 mi!!ion deathsyear.
=urrent!y tubercu!osis is contro!!ed by a #accine ca!!ed 1C, )aci!!us =a!mette'Huerin* (hich is a strain o% ;. bo#is.
;. bo#iso%ten responds to dia"nostic test %or ;. tubercu!osis.
Si e"tracellular proteinso% ;. tubercu!osis(ere puri%ied. Separate!y and in combinations these proteins (ere used to immuni+ed "uinea
pi"s. These anima!s (ere then cha!!en"ed (ith ;. tubercu!osis. A%ter 0'1O (ees eamination sho(ed that some combinations o% the puri%ied
proteins pro#ided the same !e#e! o% protection as the =H #accine.
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SubunitPeptide Vaccines
VACCINES
Se!ection & de!i#ery o% #accine peptides$
Dse discrete portion )domain* o% a sur%aceprotein as Vaccine
These domains are epitopesL )anti"enic
determinants* '7 are reco"ni+ed by antibodies
CA((IE( P(+$EINS
Prob!em '7 Sma!! Peptides are o%ten i"ested '7 no stron" immune response
'7 =arrier Proteins ;ae more Stab!e Q stron"erimmune response
;ae %usion protein o% carrier Q #accine peptide'7 inert carrier or hi"h!y immuno"enic carrier)hepatitis core protein*
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Attenuated Vaccines
VACCINES
Attenuated #accines o%ten consists o% a patho"enic strains in(hich the #iru!ent "enes are deleted or modified.
Ki#e #accines are more e%%ecti#e than a i!!ed or subunit )protein*#accines.
amp!e '7 Vaccine a"ainst =ho!era
cho!era is caused by in%ection (ithVibrio choleraeand is transmitted throu"hcontaminated (ater.
V. cho!eraeproduces a enterotoin (ith an A2 subunit and 3 1 subunits '7 causesdisease
Present!y the cho!era #accine consist o% a pheno!'i!!ed V. cho!eraeand it on!y !ast3'6 months.
A !i#e #accine (ou!d be more e%%ecti#e. 28
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Attenuated Vaccines
VACCINES
amp!e '7 Vaccine a"ainst =ho!era
55O bases de!etedo% A1 peptide The %ina! resu!t is V. cho!erae(ith a 55O bp o% the A peptide
de!eted.
'7 =urrent!y bein" tested. 2$
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Vector Vaccines
VACCINES
Virus as Anti"en Hene e!i#ery System EEE
Vaccinia "ood candidate %or a !i#e recombinant #ira! #accine8beni"n #irus8rep!icate in cytop!asm )#ira! rep!ication "enes*8easy to store
'7 The #accinia#irus is "enera!!y nonpatho"enic.
The procedure in#o!#es$
The 9A seuence %or the speci%ic anti"en is inserted into a p!asmidbeside the #accinia #irus promoter in the midd!e o% a non'essentia! "ene
e.". thymidine 4inase.
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Vector Vaccines
VACCINES
The procedure in#o!#es$
The p!asmid is used to trans%orm thymdine4inase neati!e cells(hich (ere pre#ious!yin%ected (ith the #accinia #irus.
(ecombinationbet(een the p!asmid and #accinia#irus chromosoma! 9A resu!ts in trans%er o%anti"en "ene %rom the recombinant p!asmid tothe #accinia #irus.
Thus #irus can no( be used as a #accine %or thespeci%ic anti"en.
'7 Mecombinant Virus
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Vector Vaccines
VACCINES
A number o% anti"en "enes ha#e been inserted into the #accinia#irus "enome e.".
Mabies #irus H protein
?epatitis sur%ace anti"en In%!uen+a #irus 9P and ?A proteins.
A recombinant #accinia#irus #accine %or rabies is ab!e to e!icitneutra!i+in" antibodies in %oes (hich is a maCor carrier o% the
disease.
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Vector Vaccines
VACCINES
=ontro! o% Vira! Vaccines Post Innocu!ation
8Vaccinia #irus is resistant tointer%eron '7 due to presence o%R3K protein
8Dse an inter%eron'sensiti#estrain o% #accinia #irus '7 de!eteR3K "ene to create mutant
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acteria! Anti"en e!i#ery Systems
VACCINES
-nti(en Gene
"acterium
-nti(en /roteins made on "acterial cell
0accinate /atient
'7 Dse !i#e nonpatho"enic bacterium(hich contains anti"en )Sa!mone!!a orepitope %rom cho!era*
8Insert anti"en "ene into %!a"e!!in "ene
8pitope is epressed on the %!a"e!!umsur%ace
'7 N!a"e!!in'en"ineered bacteria is
VA==I9
Ad#anta"e ' Jra! Administration
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Vaccine Appro#a!
VACCINES
8 one by =M )=enter %or io!o"ics #a!uation and Mesearch*:an arm o% the NA
8 Henera!!y same c!inica! tria! e#a!uation as other bio!o"ics anddru"s
8 Site to !earn more about #accines$
http$(((.%da."o#cber#accine#acappr.htm
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