Bun Vaccin

8/13/2019 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

systems 1


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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


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Types o% Immunity$

VACCINES


'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


-# $%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


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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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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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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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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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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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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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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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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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.

3%


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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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