CNG NGH S N XU T VACXIN(Vaccine prodution technology)I. KHI NIM
V MN HCCngnghsnxutvacxin(vaccineproduction
technology)lmtmnkhoahcnghincu cong ngh sn xut vc xin dng phng bnh
truyn nhim cho ng vt v con ngi v mt smcchkhc,nhmphcvisngv bo v sc
khe ca con ngi.Ni dung chnh ca mn hc bao gm: 1. Tm hiu v lch s v
phn loi vacxin2. Nghin cu cng ngh sn xut vacxin3.Nghin cu cc quy
trnh kim nghim vacxin4.Nghin cuphng php s dng vacxin.7. Ti liu hc
tp+ Gio trnh Min dch hc ng dngNguyn B Hin - Trn Th Lan HngNh xut bn
Nng nghip, H Ni+ Gio trnh Min dch hcNguyn B Hin Trn Th Lan Hng8. Ti
liu tham kho+ Min dch hc V Triu An Jean Claude HombergNh xut bn Y
hc, 1997+ Min dch D ng hc c s V Minh ThcNh xut bn i hc Quc gia H
Ni, 2005+ Min dch hcNguyn Ngc Lanh, Vn nh HoaNXB Y hc, H Ni, 2006 +
Vi sinh vt -Bnh truyn nhim vt nui Nguyn B Hin,Nguyn Quc Doanh, Phm
S Lng, Nguyn Th Kim Thnh, Chu nh Ti. NXB Gio dc, H Ni, 2008Chng
IKHI NIM V PHN LOI VACXIN- Mc tiu : Nm c c tnh, thnh phn v cch phn
loi vacxin-Kin thc trng tm :Khi nim v nguyn l ca vacxinc tnh c bn
ca vacxinThnh phn ca vacxinProteosom, liposom v cocletPhn loi
vacxinI. LCH S PHT HIN V DANH PHP Vacxin c chc nng to MD cho c th
ngi v ng vt chng li cc bnh truyn nhim.Txaxa,connginhnthycnhngbnh
truynnhimchgpmtsloingvtvtrong cngmtvdchcthccthmcnng,ccth mc
nh.Mtkhc,cnhngbnhsaukhibbnhquakhith vnhvinkhngbmcli,tclconngibitti
nhng g m ngy nay chng ta gi l MD.i vi cc bnh truyn nhim nguy him,
con ngi c mt qu trnh u tranh phng chng ginh git ly s
sng.Ngaytkhissngxuthin,trongsu tranh sinh tn ca cc loi sinhvt, bnh
tt xut hin, ccloisinhvttc ng lnnhau,gyraqu trnh bnh l. c bit l s tc
ng k sinh ca cc loi VSV v KST ti cc ng vt bc cao, gy ra nhng bnh
tthimngho,toranhngvdchthmkhcv cp i nhiu sinh
mng.ginhgitssng,conngitm mibin phpnhmhnchnhngtcng chica cc i tng gy
bnh.Bnh di U MAHerpessimplexHPVAIDSQuai bzonaBnh phong Un vn ngi
lnGiang maiphngchngbnhdi,nhkhoahcngiHyLp
(384322trcCN)nghchtbtchcbch di cn.Vi bnh u ma Ly vy mn u ma phi kh,
tn nh cho ngi lnh ht gy bnh nh, to MD. Phng php ny mang li hiu qu
nht nh nhng nguy himlkhngkimsotcliulngnncthgy cht ngi hoc to ra dch
trong cng ng.Nm1798,EdwardJenner,mtthythucvng Gloucestershive (Anh)
dng dch m trong mn u b chng cho ngi to
MD.ylphtminhquantrngtrongsphttrincaMD hc,m u cho nghin cu v kh nng
bo v c hiu ca c th chng li cc tc nhn gy bnh. Jenner: (t
1796)Sdngccvirus cngccang vtgymindchcho ngi. Sau , L.Pasteur: (t
1800) Trnc snych tothnhcngcc vcxin phng bnh Di, nhitthnvthuyt trng.
ghi nhn, trong hi ngh v danh php quc t, ngi ta ngh gi tt c cc ch
phm sinh hc cnguynlphngbnhnhvyvimttn chunglvacxin xutphtttvaccinia
tn ca virus u b.Danh php gm 2 t ghp: t u: vacxint sau: tn bnh Hin
nay cc thut ng v cc sn phm sinh hc dng trong th y thay i gia cc quc
gia. M: V d: OThutngvacxin dngchnhngsnphm
chavirushocnguyntrngsnghaynhc c, vi khun sng hoc cc axit nucleic.
OCcsnphmchavikhunchtvccVSV khc c gi tn nh bacterin, cht chit ca vi
khun(bacterialextract),ccchtdinv (sub units), c t vi khun (toxoid).
Chu u: OCc sn phm dng trong th y c gi l cc snphmsdngchongvtnhmtora
MD ch ng hoc b ng hoc chn on tnh trng MD.Trongchngny,thutngvacxin
baogm tt c cc sn phm to ra kch thch sinh MD ch ng cho c th ng vt
chng li bnhVic s dng ny ph hp vi thut ng quc t, khng lin quan n: -
Cc sn phm sinh hc sinh MD th ng - Cht kch thch MD - Cht iu tr d ng
hoc chn on bnh.Vacxin c coi l thnh tu v i nht ca y hc hin i. Cng tc
tim chng c thc hin tt c cc qucgiavthcstrthnhtmlchn phng chng nhiu
bnh truyn nhim ngi v ng vt. Tuy nhin vn cn nhiu bnh truyn nhim him
ngho do cc VSV, c bit l do virus gy ra vn cha tm c vacxin d
phng.Hinnay,vicnghincucitoccvacxin hinc,chtoccvacxinmianglmctiu phn
u ca cc nh khoa hc.Qu trnh pht sinh v ly truyn ca bnh truynnhim
Chut Ngi Ong Rui Ln b bnh G b bnh Vt b bnh bbnh n ln ntru b n Vt ng
2.1. Khi nimTheo quan im trc y:OVacxinlmt chphmsinh hc trong cha
chnh mm bnhhockhngnguyncammbnhgyramtbnh
truynnhimnocnphng(nulmmbnhthphi c git hoc lm nhc c bi cc yu t vt l,
ha hc v sinh vt hc). OKhisdngchongvt,vacxintoramtpngmin
dchchnggipngvtchnglicsxmnhim ca mm bnh tng
ng.Cchhiunychnhthnhtrncsthctsn xut
vacxinOVd:vacxinnhitthnclmtvikhunnhitthn nhc c, vacxin phng lao c
lm t vi khun lao bin d(BCG),vacxinthuyttrngclmtvikhunt
huyttrngcvhot,vacxinunvnclmt ngoi c t c gii cNgy nay, khi nim v
vacxin c s thay i. ON khng ch cn l ch phn t vi sinh vt hoc k sinh
trng c dng phng bnh m cn c lm t cc vt liu sinh hc khc (khng vi sinh
vt) v c dng vi mc ch khng phng bnh.V d: vacxin chng khi u lm t t bo
sinh khi u, vacxin chng th thai lm t receptor ca trng Nhng d l
vacxin c ch to t vt liu no v c dng vi mc ch g th thnh phn buc phi c
vacxin l khng nguyn v khi a vo c th ng, khng nguyn s gy ra p ng min
dch.Nh vy hin nay vacxin c hiu vi khi nim rng hn:
OVacxinlchphmsinhhccha khng nguyn c th to cho c th mt
pngmindchvcdngvi mcchphngbnhhocvimc ch khc.1.3. Nguyn lVacxin to ra
trong c th sng mt p ng MD ch ng. H thng MD ca c th hot ng, sinh ra
KT c hiu chng li nhng Epitop ca yu t gy bnh. C th s dng vacxin xut
hin trng thi MD thu c ch ng nhn to c kh nng chng li s xm nhim ca yu
t gy bnh tng ng.1.4.c tnh cb n c a m t vacxin Vacxin phi c4 c tnh c
bn :O Tnh sinh MD hay tnh mn cm
(immunogenicity)LkhnnggyrapngMDdchth hoc t bo hay c hai.
TnhsinhMDphthucvoKNvcth nhn kch thch. CnghalphthucvotnhlcaKN,
ngacaKNvc aca micth ng vt.O. Tnh KN hay tnh sinh KT Mtvacxin
khiavocthphickh nng kch thch c th sinh ra KT.
YutgybnhcthcnhiuEpitop khc nhau. Trong c th c Epitop qu nh (Hapten)
khng c tnh sinh KT, mun chng sinh KTcn i chng thnh ctnhKN,bng cch
kthpchngvimtproteinmangtiv hi.. Tnh hiu lcL kh nng bo h ng vt sau
khi c s dng vacxin.Mtvacxinavocth,nhiuKTc toranhngkhngphiloinocngc
hiulctcltiuditcyutgy bnh.DoyutgybnhcnhiuEpitop khc
nhaunntrongbochvacxintrctin philmsaochopngMDchngli nhng Epitop thit
yu TrongNCsnxutvacxinhinnayngi tacgngphnlpnhngKNhayEpitop
thityulmchovacxincthun khitvtinticthtnghpc chng.O V d: Vi virus
Gumboro: protein VP2 Virus cm gia cm :H v N Virus vim gan B: HBS(
KN b mt )Hiulccavacxincnhgiquathc nghim nhng ch yu nh gi trn thc a
sau khi tim chng McMDqunth,cthda vo lngKT trung bnh trong HT v t l
bo h trong qun th.TrnVTN:nhgimcpngMD sautimchngvacxinvhiulcbohl ng
vt qua th thch cng c.OTh nghim thc a: Vacxin c tim chng cho mt qun
thV , nh gi kh nng bo h khi ma dch ti ng thi th thch cng c 1 nhm
ngu nhin.Vacxin c hiu lc l gy c MD mc cao v bo v c th ng vt lu
bn.Tuynhin,hiulcca1vacxinphthuc vo nhiu yu t: bo qun, vn chuyn v k
thut tim phng. V vy, ngi ta xy dng 1 mn khoa hc
migilvacxinhc(vaccinology)mc chlnghincumibinphptlcsn
xutnlctiudngtngtnhhiulc ca vacxin.O Tnh an ton:y l c tnh rt quan
trng.Sausnxutvacxinphiccquankimnh nh nc kim tra v: v trng, thun
khit v v c.OV trng : Khng c nhim cc VSV khc.OThun khit: Khng c ln
cc thnh phn KN khc c th gy ra cc phn ng ph.OV c : Liu s dng phi thp
hn rt nhiu so vi liu gy c.VacxinphicthtnhantontrongphngTN, thc a,
quy m nh v i tr.Tn sut v mc nng nh ca cc phn ng ph
nucphicxcnhtrckhicemra dng chung, nhng vn phi c theo di cn thn.1.5.
Cc loi vacxin+ C th chia vacxin lm cc loi sau:Vacxin cht (v
hot)Vacxin sngVacxin di n vVacxin th h mi sn xut bng cng ngh gen1.
Vacxin chtL loi kinh in nhtNguyntcllmchtyutgy
bnh(virushocvikhun)nhngvn gictnhmncmvtnhkhng nguyn.Vacxin loi ny ch
yu gy p ng MD kiu dch th.+ Phng php lm cht yu t gy bnhC 2 phng
php-Phng php ha hc: Dng cc ha cht . Nh formol git cht vi khun.V d:
vacxin t huyt trng ln v hot . Vi virus c th dng cccht kh c hot tnh
cao nh Ethylenamine, propiolacton. Nhng ha cht ny v hot hon ton
virus nhng khng lm bin i protein cu trc.V d: vacxin bi litdng tim
ngivacxin di bt hot dng propiolactonvacxin LMLM
dngEthylenamine-Phng php vt l:sc nng, tia x (X, UV).u, nhc im ca
vacxin chtu im: Khng c, khng gy nhim mi trng,tnh an ton cao.Nhc
im:-Thi gian MD ngn do lng KN c nh v t dn-Liu lng tim ln do kh tim
v d gy p xe.-MD xut hin chm, gy MD t bo km.-Khng can thip trc tip
vo dch-Phi a vacxin nhiu ln, tng nguy c d ng.Do l mm bnh cng c, nu
bt hot khng tt s c nguy c pht dch. V d: 1 v dch bi lit M do s dng
vacxin bi lit v hot nhng khng trit .1.5.2. Vacxin sngLvacxincsnxutt
chngvirushayvi khuncnsng,Khngcntnhgybnhcho ng vt c tim phng C kh
nng gy p ng MD mnh, chng nhn lntrongcthvtchvtoraskchthch ca KN
trong mt khong thi gian.Vacxin sng bao gm: Vacxin nguyn cVacxin v
cVacxin nhc c+Vacxin nguyn c: Dngchngvirusnguynccquanhtloi ng vt
khc.Vd:Dngvirusublmvacxinphng bnh u ngi.a vo c th virus c c lc hoc
gim mt phnclctheoconngthcnghim:c lccavirussgimikhichngc avo
cththeongthcnghim(khnggings xm nhp ca chng trong t nhin).
Vd:Timphnghichngvimphi ngi bng adenovirus sng.Vacxin v c (vacxin
nhc c t nhin): Vacxin c sn xut t nhng chng VSV v c phn lp trong t
nhin.Vacxin nhc c ha: c sn xut t nhng chng VSV sng c
clcyu,khngckhnnggybnh cho ng vt c tim chng.Cc chng VSV ny c lm gim
c lc bng cc phng php: vt l, ha hc, sinh vt hc v cng ngh gen.Phng
php lm gim c VSV+ Gim c bng nhit :VSVgybnhthngnhycmvit0;Nunuicy
chngnhitkhngphhp,VSVsgimclc nhng vn gi c tnh KN.V d:
OVacxinnhitthn:nuiVK42430C/15-20ngy,VK
mtkhnnghnhthnhgipm,clcgim,sdng lm vacxinOVacxin Sabin dng ung chng
bi lit: Chn cc chng virus bi lit t bin, cho nhn ln nhiu ln trong t
bo thn kh, nui cy T0 thp. Virus c th nhn ln trong tuyn nc bt ng tiu
ha nhng khng xm nhp c vo m thn kinh do khng gy chng bi lit na.+Gim
c bng yu t ha hcOV d: Vacxin BCG (Bacterium Calmette Guerin)L mt
chng TKlao bM.T. bovinus c c lc cao, nui cy trong mi trng c mt b
trong 13 nmSau 230 ln cy chuyn, vi khun khng cn c, c s dng sn xut
vacxin BCG.+Gim c bng phng php sinh vt hc . Phng php gim c VSV c in
. Phn ln vacxin virus s dng cho ngi, ng vt sn xut theo phng php
ny..NgitacychuynVSVnhiuiquami trng t cm th . VSV khng iu kin thc
hin y chu k sng,gythayihgen thayiclc, kh nng gy bnh.V d: O Viruscng
c DTL timtruyn lin tc 155 i qua th s thu c ging virus nhc c
DTL.OVirusdchtvtchuyn4146iquaphi g.OVirus vim gan vt typ I cy chuyn
54 i qua phi g.OVirusbilitccychuynnhiuiqua mi trng t bo thn
kh.OVirus si c nui cy qua t bo x phi g.+u im ca vacxin sng:-To MD
nhanh, mnh; MD tn ti lu bn do VSV vn c kh nng nhn ln v tn ti lu
trong c th c tim chng.- To min dch t bo cao hn vacxin cht.- C th
dng can thip trc tip vo dch.-Liu lng t, d tim chng.+Nhc im ca
vacxin sng :- Mc an ton thp do t bin dn n s tr li cng c.- Tp nhim
virus trong nui cy t bo.V d: T bo thn kh c th tp nhim vi SV40
(Simianvirus)- Kh bo qun, chi ph ln.-M t sloa i khng s dng c cho ng
vt mang thai.- Khng dng cho nhng vng an ton dch.Bng so snh gia 2
loi vacxinLoi vacxinCh tiu Vacxin sngVacxin cht - Phng thc sn xut-
Tnh n nh- Liu lng- S ln a vacxin- Cht b tr- Thi gian min dch- p ng
MD t bo- S tr li cngc n ginTng i n nhThp1 lnKhngDiTtC th c n ginn
nhCaoNhiu lnCNgnKmKhng 1.5.3. Vacxin di n
vLvacxinchaKNtngitinhkhitphnlpt virus hay vi khun gy
bnhMtsVKgybnhbngct:Cl.tetani,
Corynebacterium.diphtheria,ngitanuicyVK, chit tch c t, gim c bng yu
t ha hc hoc vtltheonguynlcavacxincht.Ccctmt
hottnhcgilgiict(anatoxin)vc dng lm vacxin.Phy
khuntgybnhnhEnterotoxin,ctny gm1 di n v A rt c v 5 di n v B khng
c,nhngBlickhnngsinhkhngthbov nnngitanuivikhun,tinhlcEnterotoxin,tch
di n v B dng lm vacxin chng bnh t.+ 1 s bnh do virus gy ra, vacxin
khng dng tonbhtvirusmchdng1vithnhphn ca virus: protein capxit hoc
glycoprotein v ngoi do vacxin cn c gi l vacxin di ht (subvirion). +
Khng dng virus nguyn vn l do:ONhiuloiviruskhngckhnngnhnlncc t bo
nui cy (virus vim gan B).OMtsvirusccoilrtnguyhimnnkhng
mboantonkhisnxutkcvacxinsng hoc cht (HIV)OMt s vacxin nu sn xut t
virus nguyn vn c thnhhngncthdogyphnngph (vacxin
cm).Lu:victngtinhkhitca vacxin c th dn n mt tnh sinh MD hoc s b
ccenzymphhytrckhikchthch min dch.Vvyloivacxinnyihiphicvt
manghaychtbtr,vdnhmui nhm.Vacxindinvcmcthunnht v tinh khit hn ton b
VSV cho nntnh mn cm, tnh sinh KT v tnh hiu lc u
cao.Ccproteincapxithocglycoproteinvngoi thng gn vo receptor trn b
mt mt s loitbokch,hocthucthuyt tngbnhnhn,saulmbthot
(khngnguynbmtcavirusvimgan HBSAg)hoccthsnxutbngkthut ti t hp
ADN...Cc vacxin subvirion nh: - vacxin HA chng virus cm typ A,
B-vacxin HBS chng virus vim gan B1.5.4. Vacxin th h mi sn xut bng
cng ngh gen Khi nimNhng tin b v KH - KT trong lnh vc VSV, MD hc,
sinh ha , c bit l k thut gen hc vcngnghsinhhcphntmramt
hngngdngmilnghincusn xut cc loi hnh vacxin bng cng ngh gen.
Nhngvacxintorabngphngphptrn gilvacxinthhminhmphnbitvi
ccloivacxinccnghincusn xutbngphngphpcngnghtruyn thng.Mt vacxin c gi
l vacxin th h mi philthnhphmcamtquytrnhc scanthip,sdng,thaotccacng
ngh gen.Hinnaynhiuloivacxinthhmi vangcavosdngchiu qu, gp phn vo vic
phng chng bnh tt cho ngi v ng vt. Nguyn lTrongmtloivacxin,yutquytnh
tnhsinhMDchnhlphnproteinc bit c trn b mt ca VSV gy
bnh..ThnhphnproteinnycgilKN vdomtgenhaymtsgenctrong
hgencaVSVgybnhquytnh tng hp nn..Nhnggenchutrchnhimtnghp protein KN
c gi l gen KN.NutchgenKN khivtliuditruyn caVSVrighpvomththng
plasmidvectorthchngnothgen KN ny vn hot ng nh khi tn ti trong h gen
ca VSV ch v phn t protein KN c tng hp ra vn c th c chc nng nh c, tc
l c tnh sinh min dch. ChphmproteinKNctorabng cngngh gennhthcgil
vacxin th h mi vacxin cng ngh genPhn loiVacxin th h mi c nhiu loi.
Cn c vo ngun KN nhn ln c hay khng nhn ln trong c th ng vt, ngi ta
chia vacxin th h mi lm 2 nhm:a. Vacxin c KN sng c nhn ln:
CVacxintithpcvectordn truynC Vacxin axit nucleic (vacxin ADN)C
Vacxin xa gen c b. Vacxin c KN khng nhn ln:C Vacxin cha KN l
protein sn xut bng k thut genC Vacxin n cC Vacxin peptit tng hp a.
Vacxin c KN sng c nhn ln, bao gm:a. Vacxin c KN sng c nhn ln, bao
gm:C Vacxin ti t hp c vector dn truynLoi vacxin ny cha 2 thnh phn
chnh:-onADNchagenmhachoKNchnh c tch ra t VSV gy bnh.-H gen ca
vector dn truyn.Ngi ta tch ri gen KN t VSV gy bnh ri ghp vo
hgencavectordntruynlplasmidhayVSVri a vo vt ch. L SV sng nn khi gy
nhim, chng s nhn ln do ngun gen KN v sn phm ca gen KN l protein KN
lun c sn xut ra to MD lu bn cho c th.+ Cc vector dn
truyn:Hinnayccvectordntruyncchn thng l nhng sinh vt: - Vi khun -
Virus - Nm men - Thc vtThngcthnhnlncnhiuloi ngvtvclmgimchocv c bng
k thut gen.Vi khun S. typhimurium: L loiVKkhngc,cchnlmvector dn
truyn v c cc u im: - D s dng qua ng tiu ha. - C th tn ti v nhn ln t
chc Lympho ngtiuha,cungcpproteinKNbn vng gy p ng MD ton din: dch
th, t bo v min dch cc b.- Vic nui cy VK ti t hp gen ny d thc hin v
thi gian sn xut rt ngn.Hin nay S.typhimurium c s dng ph
binlmvectordntruynsnxutcc vacxin:cm,vimganB,stxuthuyt,t, lin cu
khun, KST st rt...NgoiS.typhimurium,cnsdngvikhun E.coli v mt s loi
nm men nh: - Pichia pastoris - Saccharomyces cerevisiae + Virus u b
( vaccinia):ThucnhmOrthopoxviruscsdng mtthikdilmvacxinphngbnhu ma.H
gen ca virus u c 200.000 nucleotitCkhnngtipnhnnhiugenngoilaic
di25.000nucleotit lvectorltng sn xut vacxin a giMt khc virus u:- C
kh nng gy nhim vo nhiu loi vtch nhng khng gy bnh- C th nhn ln trong
nhiu loi t bo nui cy,thmchnhiudngtbom chngkhnghonthincchutrnhnhn ln
khngbdungbo thuntinlm vector. Virus u ti t hp c th biu hin gen KN
smvsnxutraproteinKNgypng MD ton din. S to vacxin ti t hp vct dn
truynNui cy t bochn lcvirus u vectvirus uti t hpgen vacxinkhi pht
ATGkt thc TAActnigen vacxinim mmv tr ctvng khi ngPlasmidPlasmidti t
hpCc bc to vacxin ti t hp cvect dn truyn:-Ct on gen vacxin -Gn on
gen vacxin vo Plasmid-Chuyn np cc Plasmid gn gen vacxin vo virus u
virus u ti t hp.Hin nay s dng virus u lm vect dn truyn sn xut mt s
vacxin ti t hp phng bnh cho vt nui:-Gi gen m ho protein F ca virus
Newcastle vo virus u to vacxin ti t hp phng bnh Newcastle-Gi gen m
ho protein HN vo virus u to vacxin ti t hp phng bnh cm gia
cm.Vacxin vim gan B v i gen m ha bm t HBS Ag (Hepatitis B surface
Antigen).C Vacxin axit nucleic (vacxin
ADN)VacxinthnhphnchnhlADNcaplasmidtit hp cha gen KN.GenKN
caVSVgybnhcgnvoplasmid. aplasmidtithpvotrongtbocth bng sng bn
gen,hoc vi tim.Vacxin thng c tim vo c th a gen trc tip vo mt s t bo
c. Khivotrongtbo,ADNcaplasmidtithp c nhn ln, protein KN c sn sinh
trc tip bi t bo vt ch, chng kch thch c th sn sinh MD.+u im ca
vacxin ADN:- Gen KN biu th mnh, thi gian sn xut KN lu to MD mnh,
bn, khng cn tim nhc li.-VacxinADNrtantonvgenccloitr, hiu lc n nh, d
bo qun, thun tin cho vic s dng, c ngha kinh t.- To MD tt nhng c th
b suy gim MD v c th suy nhc.-C th thit k mt vacxin a gi ( Trn cng 1
plasmid gn nhiu gen m ha hoc trn nhiu loi plasmid c cha ADN m ha
cho cc loi proteinkhc nhau. Hn hp vacxin ADN ny khng b
nhhnglnnhau,nhthsnginhac tin trnh tim chng.+Nhc imThc
nghim:avacxinADNvocthV ,sphnb ADNvacxintrongtbokhngtcmc ti a.
Mtkhc,nuADNvacxinnhpvohgen caV ch s:- Gy hu qu v di truyn cc th h
sau- C th gy t bin t bo ung th - c ch hot ng ca gen chng ung th,gy
bin i t bo dn n t MD.VacxinADNthucthhminht,ccoi l loi vacxin c trin
vng ln.Hintivacxinmicnghincuth nghim trnV :OVacxin ADN cha gen
HBsAgOVacxin ADN cha gen KNch yu ca HIVOVacxin ADN cha gen H v N
chng cmC Vacxin xa gen cVacxinchayutgybnhclmnhcc bng k thut gen ct
b gen c.V d: Otoraginggcsnxutvacxincmgiacm,
hinBYtvVinKHCNVitNamnhpngoi chng virus vacxin NiBRG-14 t Vin Tiu
chun v kimnghimdchsinhphmqucgiaVngquc Anh thng qua WHO. OChng
NiBRG-14 to ra bng ghp 6 gen ca chng /PR8/34(H1N1)vi2genH5N1cachng
A/Vietnam/1194/2004 (H5N1). ORinggenH5bloi12nucleotitmha4a.athuc
vngc,chngvirusnycthnuicytrnphi g.Vacxin Aujeski cng l 1 vacxin nhc
c kiu ny.b. Vacxin c ngun gc KN khng nhn lnL loi vacxin v hot sn
xut bng k thut gen C Vacxin cha KN l protein sn xut bng k thut
genLoivacxinnycsnxutbngcchtchgen KNttcnhngybnh,ghpvohgencamt loi
VSV lm vector dn truyn Nui cy VSV ti t hp ny trong MT thch ng nh h
thng bioreactor hocthit b ln men ln, lng protein s c sn xut vi s
lng nhiu sau chit tch protein KN lm vacxin.C Vacxin n
cDngthcvtlbioreactorsnxut dc cht protein l mt xu th pht trin ca cng
ngh sinh hc. Nhiu gen m ha KN virus c chuyn vo thc vt v biu hin vi
hiu qu cao. Snxutvacxinnclhngnghin cu c trin
vngVacxincthcvtsnxuttrongnhng phn n c nh l, c, qu v ht.Nm 1990
vacxin n c u tin c sn xut t thc vt Do 2 nh khoahc Curtiss v
CardineuCardineu khi biu hin thnh cng protein KN b mt A ca
VKStreptococcus mutans cy thuc l. Sau nhiu vacxin TV c cng b sn xut
trn nhiu loi cy khc nhau: - Rau dip - C chua - Khoai ty, la m, u
tng v ng... Mt khc, gi l vacxin n c l cp n s chp nhn ca c th ng
vt:. Vacxin bn vng trong dch tiu ha. Vacxin khng b phn hy
.CkhnngkchthchpngMD mnh.NgitadngthutngPlanedible
vaccinechloivacxinncsn xut t thc vt bin i gen ny.Nguyn l sn xut
vacxin n c: Vacxin n c l loi vacxin tiu phn bao gm mt hoc nhiu chui
polypeptit ca protein KN trong VSV gy bnh. Ngi ta chn lc nhng gen m
ha cho cc thnh phn ny, a vo vector (plasmid hoc vi khun (
Agrobacterium tumefaciens). Da vo h thng di truyn thc vt khuych i
gen v biu hin thnh cc protein KN mong mun trong cc b phn n c ca thc
vt. Cc thnh tu nghin cu vacxin n c c cng bNgun
proteinProtein/Peptit i tng thc vtp ng min dchTc gi, nm bo
coE.coliTiu phn B c t km chu nhit LT-BThuc lKhoai tyKT dch th v KT
t bo theo ng ung v nHagetal, 1995Vibrio choleracc t tTiu phn BKhoai
ty Cho n Arakawa, 1998Virusvim gan BHBs-Ag Thuc l Cha th nghim
Mason etal, 1992Virus diGlycoproteinC chua McGarvey etal
1995Cl.tetaniNgoi c t Lc lp thuc lCho n Tregoing etal, 2003C Vacxin
peptit tng hp:L vacxin thnh phn ch cha duy nht polypeptit KN (8 20
axit amin)Do ch c cc epitop KN nn khng c kh nng kch thch sinh MD v
vy sau khi cc peptit c tng hp, ngi ta phi gn chng vo cc gi l cc ht
polyme c kh nng hp ph cao.V d: vacxin peptit phng bnh LMLM, vic bo
h t cbngcchtimchongvtmttphpcc chui peptit KN gm 20 axit
amin.+Vacxin peptit c u im:OSn xut v kim sot cht lng n gin.OKhng c
cc thnh phn khng cn thit nh nucleic, protein ngoi lai do t c.OC th
thay i theo s bin i t nhin i vi nhng virus khng n nh nh virus cm.OC
tnh kh thi thm ch trong trng hp khng nui cy c virus.On nh, gi thnh
h.+Nhc im ca loi vacxin : OSinh min dch c th km so vi cc vacxin v
hot truyn thng.OBt buc phi c cht b tr.OYu cu tim nhc li.S tm tt phn
loi vacxin Vacxin s ng Vacxin Vacxin v ho t Vacxin nh c c haVacxin
s ngnguyn c Vacxin s ngv c Xa gen c Thchng nhi t th p Nh y c m nhi
t Qua v t chtrung gian khng c m th Ti th p gen Vacxin vector dn
truy n Vacxin ADNVacxin d in vVacxin nguyn venVacxin n c Ch a
protein KNt ng h p b ng kthu t gen Tinh ch b ng k thu t gen Tinh
chb ng ngu n SV ch trong tnhin 1.6. Cht b tr+Khi nim:
OChtbtrlnhnghpchthahccthm votrongvacxinnhmlmtngkhnngkchthch MD v
tng hiu lc ca vacxin.ONm1930,Ramonlngiutinnghincuv
chtbtr.ngchngminhbngthcnghim rngkhibsungchtbtrvovacxinthhiulc ca
vacxin cao hn.* Cc cht b tr: Gm 3 loi chnha. Cht b tr v c: L nhng
ht mn ca mui silicat hoc mui sunfat, mui phosphat hoc ht bt talk,
than hot tnh.V d :O Alumin hydroxit Al(OH)3O Sunfat alumin kali
AlK(SO4)2.12H2OO Phosphat aluminum Al(PO4)Trong th y, ngi ta hay
dng cht b tr l AlK(SO4)2.12H2O (gi l keo phn) trong cc vacxin vi
khun v hot.b. Cht b tr hu c: Dng cc hp cht hu c khi trn vo vacxin s
c tnh cht huyn ph trng nh sa nn gi l nh du.V d:Du khong, sapolin Du
thc vt, m ng vtFreund (du khong paraphin + BCG cht)Nhng Freund t
dng v hay gy mng m ko di hoc vim khp. i vi nhng KN phn t lng nh ngi
ta c th gn vi protein mang ti tng hp hoc cht mang t nhng ht m nh gi
l liposon..c. B tr l sinh vt:Thng dng l xc ca mt s loi vi khun
nh:-M. tubercullosis -Sal. typhimurium.Cng c th dng ni c t ca vi
khun nh Lypopolysaccarit* Tc dng ca cht b
tr-KchthchMDdobnthnchtbtrgy phnngvimnh,koccithcbov cc t bo MD khc
ti.-Hp ph KN, khoanh vng KN, lm chm qu trnh gii phng KN ti v tr
tim, do KN tn ti lu trong c th, ko di s trnh din KN.-Kch thch s hot
ng ca APC qu trnh phn tch, trnh din KN t hiu qu.-Cht b tr SV: C tc
dng kch thch t bo MD..Xcvikhunlaolmtngtngtcgiat
bolymphovTB,dolmtngpng MD t bo .LPS tc ng n t bo lympho B lm tng
qutrnhphnbotoplasmoxytedotng hm lng KT dch th c hiu.
