PRE F A CE Wh a t is a v accine? P r oper t ies of g ood v accine T ypes of v accines Ad v a n t a g es of r e c omb i na n t c o n v e n tional v accines R e c ombina n t virus v accines r e c omb i na n t v accines Fu t u r e P o t e n tial R e f e r ences • • • • v accines o v er • or li v e • •
WH A T IS A V A CCINE? A p r epa r a t i on of k i l l ed or w ea k ened mic r oo r g an i sm th a t is gi v en t o a pe r son o r al l y or i n je c t ed in o r der t o p r e v e n t d i sease. • E d w a r d Jen n er demon s t r a t ed th a t a pe r son i n o c u l a t ed i n t o the skin with c owp o x w as p r o t e c t ed a g ain s t sm a ll p o x and he thus d e v eloped the pr i ncip l es of v a c cin a tion in 1796. In 1881 Louis P a s t eur hono r ed Jen n er b y nami n g the p r o c essing ‘ ’ v a c cin a tion’’ and the su b st an c e used t o v a c cin a t e w as a ‘ ’ v a c cine’ ’ . •
• Principle of a va c cine is to ind u ce a p rimary res p o n se in the va c cin a ted su b ject so that follo w ing the e x p o sure of a p a tho g en,a ra p id sec o nd a ry immune res p on s e is ge n erat e d lea d ing to ac c eler a ted elimin a tion of the o r g a nism a n d pr o tection from clinic a l dis e as e . Suc c ess d e p e n d s on t he g e n e ration of me m ory T cells a n d B c e lls a n d pr e se n ce of n e utr a lizing a n tibo d y ser u m . •
P r operties of a g ood v accine • Abil i ty t o elic i t the app r opri a t e immune r esp o nse f or p a t h o g en. t h e particul a r • • • • Lo n g t erm Sa f e ty S t abil i ty p r o t ec t ion In e xpe n si v en e ss
T ypes • Live vac c i n es of v accines • Ki l led or wh o le o r g a n i sm v ac c i n es • Su b u n it va c ci n e s -pur i fied or re c om b i n a n t an t i g en • Recombinant vaccines • DNA v a cc i n e s
Th e se v a c c in e s are prepar e d from atte n u a ted str a ins that are almost or c ompletely d evoid of pat h oge n icity but a re capab l e of ind u cing a protective i m m u ne respo n se to the body. Th e y m u ltiply in h u m a n host a n d pr o vide • • c o ntin u ous ant i ge n ic stim u lation over a period tim e . For exa m ple typ h oid v accine s . of •
Killed whole o r g anism v accines • It is a v a c c ine th a t is p r o d u c ed by g r o w ing the o r g a ni s m a n d th e n killing or i n a cti v ati n g it with h e at a n d/ o r c h e m ic a ls. • Th e se are used w h en s a fe live v a c c in e s are not a v ail a ble • For e x a m ple in a cti v at e d p o lio v a c c ine • Ra b ies v a c c ine
Subunit vac c ines are d e fined as those vacc i nes conta i ning one or more pure sem i -pure ant i gen. or These are of recomb i nant recomb i nant three types, toxoids, subunit va c cines and non subunit va c cines.
T o x oids • In some diseases l i ke diph t heria and te t anus it is not the gro w th of the bacterium that is dan g erous, but the protein toxin that is l i berated by i t . • T reat i ng the toxin with formaldehyde den a tures the protein so t hat it is no longer dan g erous. • The inactivated toxin is called as tox o id. • For example, D P T vac c ine also called as trip l e vac c ine.
• SUBUNIT V ACCINES (NO N -RECO M BINAN T ) • Co n stitue n t pr o teins of ba c teria or virus are isolat e d a n d p u rified • Ad v ant a ges: • Defi n ed Com p osition • V ari o us d e livery syst e ms av a ilable • Disa d v a ntage s : • Antig e ns mu s t be pr o d u c e d a n d p u rified by cultivation of a pat h og e n • Multiple d o ses typi c ally re q uir e d • Adj u v a nt n e e d ed
Subunit rec o mbinant vaccin e s These vaccin e s a r e those in w hich g e nes for des i r e d an t i g ens a r e ins e rt e d in t o a vec t or, usua l ly a virus, th a t has a v e ry l o w v i rul e nc e . The v e ctor e x press i ng the an t i g en may be used as the v a ccin e , or the an t i g en may be purifi e d and inj e cted as a subunit v a ccin e . The on l y r e combinant v a ccine curren t ly in u s e in hu m ans is the Hep a t i ti s B Virus (HBV) v a ccin e , which is a recombin a nt subunit vaccine Hep a t i ti s B surface an t i g en is produced from a gene tr a nsfected in t o y e ast ce l ls and purifi e d for in j ec t i on as a subunit v a ccin e . This is mu c h s a f e r th a n using a t t e nuated HBV, which could c ause l e th a l hep a t i t is or l i v e r canc e r if it r e v e rt e d to i t s v i rul e nt phen o t y pe. R e combinant DNA t e chniqu e s can also be used to make saf e r a t t e nu a ted pa t hogen vaccin e s
V accine type Li v e v a cc in e s A d v a n t a g es D r a wbac k s • 1. o n e or f e w d o s es n o r m ally r e q u i r ed 2.Lo n g t erm p r o t e c tion 3. B oth c ell u lar a n d hum o r al r e s p ons e s 1. c o n t r o l led a t t e n u a tion r e q u i r ed 2. r isk of r e v e r si o n 3.poorly d e f i n ed c o m p o s ition • Kil l ed v a cc in e s 1. N o ri s k of r e v e r si o n 2. N o ri s k of t r a n smis s i o n 1.m u lti p le d o s es r e q u i r ed 2.po o rly d e f i n ed c om p o s ition • Su b un it v a cc in e s 1.D e f i n ed c om p o s ition 2 . v ari o u s d eli v e r y s ys t e m s a v ailable 1.m u lti p le d o s es r e q u i r ed 2.adj u v a n ts n e ed ed (n on r e c om b in a n t) • Su b un it v a cc in e s 1.no ri s k of p a t h o g e n i c ity 2 . d e fin e d c o m p o s ition 3 . v ari o u s d eli v e r y s ys t e m s a v ailable 4.la r g e s c ale p r od uc tion sim p li f ied 5 . furt h er g e n e tic e n gi n e e ring p o s sible 1.m u lti p le d o s es ty p i c ally n ee d e d 2.adj u v a n ts n e ed ed ( r e c o m b i n a n t)
Which V e ctor to be used? Must be c ompatib l e with host cell system (p r okaryotic vectors for p r okaryotic c ells, eukaryotic vectors for eukaryotic Needs a g ood comb i nation of cells) – – – – – strong promoters ribosome bindi n g sit e s termin a tion seque n ces a f fi n ity tag or solu b li z at i on sequ e nces m u lt i - e n z y me restr i ction site
A gene codi n g f o r an i mm u n o g enic p r o tein f r om o n e o r gan i sm in t o t h e gen o m e o f o t he r , such as vac c i n ia v i r u s is i n tr o d u c e d. The o r gan i sm e x p ress i ng t h at gene is c a lled as re c o m bi n ant. F o ll o wing i n jection i n to t h e s u b j e c t, t h e reco m b i nant will repl i c a te and ex p ress su f ficient a m o u n t s of the fo r eign p r o t ein to i n d u ce a specific i m m u n e res p o n se to t h e p r o t ein.
Advant a ges of viral vector vaccines Eli c it st r ong hu m or a l and ce ll- m edi a ted i m m une re s ponse s , re s ul t ing i n i m m unolog i cal m e m or y . Can be ta r get e d by vi r al t r opis m s for pa r t i cular ce l ls, e.g. int e stine, bra i n, et c ., inducing des i r e d i m m unit y . Can al s o encode for seve r al ant i gens from di f ferent pathog e ns, in t rodu c ing the poss i bi l ity of a sing l e vacc i ne for seve r al dis e ase s . • • • • V i r a l ve c t o rs have b e en f ound not to i n ter f ere w i th t h e pro t ec t i o n produ c ed by other types of vacc i ne s .. V acc i nes are re l atively inexp e nsive and, for so m e, ea s i l y t r anspo r table. •
Disad v anta g es • Since the l i ve vi r us b eing used i s an a ttenu a ted fo r m o f a hu m an pathog e n, there is always a r i sk of re v ersion to viru l enc e . S o m e of the ve c to r s un d er con s ider a tion, such as adeno v i r u s , • have the c apa b il i ty of transfor m ing c e lls to a c an c erous phenotype. W hile t h ese oncogenes a re re m oved, ve c tor v i r u s could reco m bine w i th na tura l ly o cc u r r ing, p a th o gen i c s t r a i n s in the en v iron m ent a n d form a new hybr i d virus w i th t r ansfor m ing prop e r t ie s . • Im m u n e response to v i ru s - infe c ted ce lls m ay c ause patholog i c a l proble m s .
C o n v e n tion a l v s R e c ombina n t DNA V accines Co n v e n ti o nal R e c ombina n t DNA v acc i n e s v ac c ines • • Chemi c al or p h y si c al i n a c t i v a t i on(ki l le d ) L a bo r a t o r y i n duced ch a n g es t o w e a k en p a tho g ens(li v e a t t enu a t ed) Is o l at e r el a t ed and R e c omb i na n t g ene r a t ed su b u n i t s or D N A v a c cines(k i l l ed) Gene de le t ed p a tho g ens V ec t or - based o r g anis m s t o del i v er f o r eign g ene • • • • des i gned a t t enu a t ed (Li v e) p r oducts(Li v e)
Fut u r e Developments • Id e nt i fic a tion and ut i l i z a tion of bet t er i m m un o ge n s as new vacc i nes for dis e ases • Bett e r vacc i ne del i ve r y m ethod s : or a l, in t ra n asal, and syste m s al l o w ing m ass vaccina t i ons • Use of i m m uno m odula t ors i n vec t o r - based vacc i ne s : C P G m ot i fs and cytok i ne s . • Expre s sion of foreign pro t eins i n plan t s and the deve l op m ent of edible vaccines • V acc i nes deve l oped for non - infec t ious agen ts : cont r ol and pr e vent canc er ; vacc i nes t o induce long la s t i ng cont r acept i on
R e f e r ences Sciencedi r ect. c om A c ademia. c om Ani m al Agricultu r e's F utu r e th r ou g h Bio t echnolo g y - Mark W . Jac k w oo d , Les l ie Hick l e • • • • Esse n tials of Clini c al Ho f fb r and Im m unolo g y - A . V