8122
2010
BdYTf
BAO
CAO
idl QUA NGElfiN Ctfl] fli
T.4l
Clp
BO
nUESM
ecu
rjNG DtJNG
QUI
TRINH
SAN
XUXT
KHANG
HIJYf
F
THANH
Sdl,
BAILE^,
ROTA StJTOWG SQ^M BBStH vAC SIN
Cbunhttind^ai:
PGS.TS.L«TMl«te
Cff quan (Td ch6c) did
hi
S«
Oil:
Trung tftm Ngbi«n c«iu
Sin
THANH SOU, BAI
LIfT,
ROTA
SlJ DVNG KIEM SpjH
VAC
XIN
Chu nhifm
de
tii:
PGS.TS.Lg
Thi Luan
Ctf
quan chu
tri
de tai: Trung
tam
Nghien
cuu
San xuat
V^c
xin
va
Sinh
pham
Y te
Cap quan
ly:
B9
Y te
Ma so de tai
1.
Ten de tai:
NGHIEN
ctru tTNG DVNG
QUI TRINH
SAN
XUAT
KHANG HUYET
THANH
sen,
BAI
LIET,
ROTA
SU"
DVNG
KIEM
DpVH
VAC XIN
2.
Chu
nhifm
de tai: PGS.TS.Le
Thj
Luan
3.
Cor
quan chu tri de tai:
Trung tam Nghien ciru, San xuat Vac xin va Sinh pham Y te
4.
Cv quan quan ly de tai:
NO
Anh Thu
Ngo Thu Huong
8. Cac
dl
tai
nhanh
(de
mi^c)
ciia de tai (neu c6)
9.
ThM
gian
th^c hi|n
de tai: tu thang 7 nam 2007
dSn
thang
12
nam 2009
Cac chir viet tat
BS (Bovin serum)
PBS
(Photphat
buffer solution)
P-S (Penixilin - Streptomycin)
MEM (Minimum Eagle Medium)
FBS (Fetal Bovine Serum)
: Huyet
thanh
be
0)
IgA
(Immuno Globulin A)
IgM
(Immuno Globulin M)
IgE
(Immuno Globulin E)
IgD
(Immuno Globulin D)
MAI
04
Vero
Hep2
Da
FIA
(Freund's Incomplete Adjuvan)
FCA (Freund's Complete Adjuvan)
WHO (World Health Organization)
: Khang the IgG
: Khang
thi
IgA
: Khang the IgA
: Khang
thi
IgA
: Khang the IgA
: Te bao than bao thai
khi
Rhesus
1994 c6 nhiem vu san xuat
v4 kiem dinh
vac xin. Hien nay Trung tam dang san xuat va kiem
dinh
vac xin Bai
liet,
vac xin Soi; nghien cuu, san xuat vac xin Rota phong
tieu
chay cho tre em. He thong
kiem dinh cua Trung Tam duoc dao tao co ban va chuyen sau phuc vu cong tac kiem
djnh
chat
lucjmg
vac xin. Mot trong nhung nguyen vat lieu co ban sit dung danh gia an
to4n
cua vac xin bin thanh pham trong phong thi nghiem la
huySt
thanh khang Soi,
khang virut Bai lift,
vk
khang virut Rota. Khang thi nay
s\jt
dung cho
thii
nghiem tim
tdc
nhan ngoai
lai
trong h5n djch vac xin san xuat.
D5ng
vie
xin"
vdi
nhiing muc dich sau:
1.
LTng dijng
vk hoan thien qui trinh san xuat
huySt
thanh dac
hiSu vurut
Soi,
Bai
lift.
Rota
sii dymg
trong
kifm
djnh vac xin;
2.
San xuit dugc
huySt
thanh khang vurut Soi. Bai
liet.
Rota dat tieu chuin co
sd;
3.
Danh gia chat
lugng
huyet thanh ve tinh dac hieu, hieu gia so vdi
huySt
djch t6t.
Sau khi nhan
virat
tren te bao, h5n dich virut dugc dong tan, ly tam, lay
nude
noi sau do tinh sach qua dudng Sacahrose
40%,
lay can, hoa can , ly tam 15.000
vdng
/phut/40
phiit,
lay
nude
noi, dieu chinh sao cho hieu gia theo lieu gay nhilm thich hgp
ciia
timg
loji
virut:
10*'° CCID
50/0,5ml cho virat Soi;
10''° CCID
50/0,lml cho virat
B?ii
liet va
lO''"
ffii/lml
cho virat Rota.
Thd
dugc mua tii trai thd Ba vi trgng lugng tir 1,5 kg
din
vi
khang huyet thanh.
Sii
d\mg
ta
chit hoan chinh (FCA) hoac ta chit khong hoan chinh (FIA) pha
chl
h5n dich khang
nguySn,
tiiy loai
khang nguyen c6
Hch v4 lilu
ti6m khac nhau.
Doi vdi virat Sdi cd 2 phuong phap tao khang
thi,
do la phuong phap cua vien
Kitasato
Nh|t
Ban va phuong phap cua Trung tam phong
chdng va
kiem soat
b$nh
tat
CDC-Hoa
k^.
hai phuong phap
niy
khac nhau ve chuin bi khang nguyen,
va lich
tiem
Ian
nhu sau:
Tiem lin
1
ngay
0:
Tiem 2,5ml
hdn
dich virut
+
2,5
ml ta chit
FCA;
Tiem trong
da
nhilu
vj tri,
0,1
ml/1
vi
tri;
Tiem
Ian
2 ngay
7:
Tiem 5 ml virat Sdi khong cd ta chat; Tiem vao dudi da
diii
2
bta,
m6i bSn
Tiem 10 ml virat Sdi khong cd ta chat; Tiem vao
tinh
mach tai
2
ben, m5i ben
5
ml.
Phnvng
phap san xuat khang huyet thanh Bai
liet.
Rota theo phuong phap gay
d4p
ung miln djch cua Trung tam Phong
chong va
kiem soat benh tat CDC-Hoa
Ky
Thd dugc
each
ly tir 7-10 ngay, gay
dap
img mien dich 6
Ian
tiem
each
nhau 2
tuin
vko
ngay:
0:14:28:42:56:70;
84 liy mau tai 5ml
liy
mau
0:28:42:56:70:84 (Mo, Ml,
M2,
M3,
M4,
M5)
Lich
va
lilu tiem cu
thi:
Tiem lin
1
ngay
0:
Tiem
0,2nil
virat
B^i
li?t +
0,2ml
ta dugc FCA; Tiem trong
da
nhilu
vi
tri, 0,1 ml/1 vi tri;
Tiem
Ian
2 ngay
14:
Tiem
1ml
virat
Bai
lift
+
1ml ta dugc FCA; Tiem vao co
diii
2 ben,
mdi bfn
0,5 ml;
Tiem lin
5
ngay
56:
Tiem 1ml virat
Bai
lift
+
1ml ta dugc FCA; Tiem vao co
dCii
2 ben,
mSi
ben 0,5 ml;
Tiem
ISn
6 ngay
70:
Tiem 1ml virat Bai lift
+
m tim tac nhan ngoai lai trong
hdn
dich virat vacxin khi trang hoa hoan toan me
gjt
don. Tim ra lugng khang huylt thanh trang hoa hoan toan me gat don va ap ung
trong kiem dinh
vie
xin;
Khang huyet thanh san xuat ra con dugc
sii dmg
vao thu nghiem xac dinh nhan
dang virut vacxin va xac dinh hieu gia virat vacxin bang each tim don vi khang
thi ap
dung cho thu nghiem nay.
Ket qua
1.
Qui
trinh
san
xu^t
khang huylt thanh
l.I.
Qui trinh san xuat khang huyet thanh Soi
Bu&c
1. San
xudt
khang nguyen
S&i
Viras Edmonston Vero7 dugc san xuat tren te bao vero tao virat dugc ggi la
Edmonston Vero 7/P2.
benh ngoai da, huylt thanh Sdi. Tieu chuan tho
sii
dung:
Khang huyet thanh Sdi
trade klii thii
nghifm <4 don vi; Khde manh, khong
M
bit ky
bfnh ngoai da nao; Can
njng:
2,0kg
din
2,5 kg; Thd dugc
each
ly tir 7-10 ngay. Qui
trinh gay dap img mien dich tao
ichdng
huyet thanh S&i tren tho,
/"huong
phap vifn
Kitasato-Nh$t
ban
Stt
1
2
3
4
5
6
NgJy
2
bSn,
moi
b6n
2,5 ml
Tiem 10 ml virat Sdi khong cd ta chat; Tiem vao
dudi da
diii
2 ben, moi ben 5 ml;
Tiem 10 ml virut Sdi khong co ta chat; Tiem
vao
tinh
mach tai 2 ben, moi ben 5 ml
Budc3.Lay
mau
Lay
mau
kiem tra huyet thanh Sdi 3
Ian,
lin 1
trade
khi gay miln dich
mili
1;
Lan 2 lay mau tai
trade
khi gay mien dich miii 4 de kiem tra kha nang tao huyet thanh
giila
ky; Lan 3 lay mau toan bg sau 7 ngay gay miln dich miii 5 (ngay
thii
trong 30 phiit, sau do dugc pha
loang
bac 2 va
dugc trang
hda
vdi 100 dgn vi khang nguyen Sdi, hon dich trung hoa dugc gay nhiim
tren te bao vero 1 lop, sau 2 tuin doc ket qua. Hifu gia khang huylt thanh la nong do
huyet thanh pha loang nhat ma tai dd tao ra phan ling trang hoa
(tl
bao binh thudng
khdng bi huy hoai)
1.2.
Qui trinh san xuat khdng huylt thanh Bai lift
Bird^c
1.
S&n
xuat
kh^ng
nguyen
San xudt
Ididng nguyen
bgi
lift:
Nhan virut bai
lift
typ
1,
ho5c
typ II
hoSc typlll tr6n
Igc
lan
lugt
0,65
pm,
0,45
^m,
0,2
|xm.
Hon dich virut dugc sieu
Ipc
vdi c8 dac
100-200
lin va dugc sieu
li
tam 36.000
v6ng/phuf3
gid tai
4''c,
lay can, hoa
loang
c^
bing EMS, pha loang sao cho nong do virut
lO''
CCED50/0,lml.
Hon dich virut
niy
dugc chia nho va bao quan tai
-80°C
cho tdi khi
miin dich tao khdng huyit thanh Bai liet tren tho- Qui trinh Trung
torn
Phong chong vd
Kiim sodt
benh
tat
CDC-Hoa
Ky
Stt
1
2
3
4
5
6
7
Ngay
0
14
28
42
56
70
84
Lay
mau
Mo
Lay
mau tai
Ml
FCA;
TiSm
trong da
nliieu
vi tri, 0,1 ml/1
vi
tri;
Tiem 1ml virat Bai lift + 1ml ta dugc FIA;
Tiem
vao
co dui 2
bSn,
m§i ben 0,5 ml;
Tiem 1ml virat Bai lift + 1ml ta dugc FIA;
Tiem vao co
diii
2
bSn,
mSi ben 0,5 ml;
Tiem 1ml virat Bai lift + 1ml ta dugc FIA;
Tiem
vao
co
diii
2 ben,
mdi
ben 0,5 ml;
Tiem 1ml vurut Bai lift + 1ml ta dugc FIA;
Tiem vko co dui 2 ben, mdi ben 0,5 ml;
Tiem 1ml virat Bai lift + 1ml ta dugc FIA;
thanh ri6ng
rg
cua timg thd tai nhift
dp -20°C
cho tdi khi su
diing
Bit&c
4. Kiim dinh huyet thanh
Kiem tra v6 khuin
X4c
dinh hifu gia huylt thanh bing phuong phap trung
hoa
trfn tl bao Hep2
mOt
Idp. Huylt thanh dugc bit boat 56°C trong 30 phiit, sau dd dugc pha loang bac 2
va dugc trung hda vdi 100 don vi khang nguyen Bai lift, hdn dich trung hoa dugc
gjy
nhiim tren te
bao
Hep2, sau 5-7 ngay doc ket qua. Hifu gia khang huyet thanh la nong
dg huyet thanh pha loang nhit ma tai dd tao ra phan ling trang hoa (te bao binh thudng
khdng bi buy hoai)
1.3. Qui trinh san xuat khang
hnyet
thanh Rota
Budc
1.
Son xudt
khdng
nguyen
tiudng
DMEM am khong cd
trypsin, sau do cho them moi tradng co trypsin vdi ndng dp
10-20^g/ml.
Dat chai te bao da
gay
nhiem virat tai nhift dp
37°C
trong
3
ngay.
Gat hon dich virat, dong tan
3
lan, ly tam 3.000 vong/phut/30 phut bd can.
Nude nil
thu dugc sieu ly tam 25.000 v6ng/phut/2 gid tai
4°C
vdi nong dp dudng
40%.
Bd
nude
ndi,
thu
c^
va hda
c5n
vdi TNC, sau do pha loang khang nguyen thu dugc sau
cho lugng virat khoang
lO'-lO*
fiii/ml
-Qui
trinh Trung tdm Phong chSng va Kiem sodt benh tat CDC-Hoa
Ky(gi6ng
nhu qui
trinh
tiem sdn
xudt
khdng
huyet
thanh
Bai Hit)
Budc 3. Liy
mau va
thu huylt thanh(gi6ng nhu
san
xuit khang huylt thanh Bai
lift)
Budc 4. Kilm dinh khang huyet thanh
Kilm tra vd khuin
xac
dinh hifu gia khang huylt thanh bang phuong phap ELISA. huyet thanh
dugc pha loang bac 4 .
Hifu
gia huylt thanh
la
ndng do pha loang nhat
ma
tai dd xay
ra
phdn
nh4n
ngoai lai
>1.000
cho
thii
nghifm nhan dang
virat Sdi
Dac hifu bang
thii
nghiem nhan
dang qua ky thuat miln dich huynh
quang
2.2.TiSu
chuan
khing huySt
thanh Bai liet
Tieu chi danh gia
Vdtrung
Hifu
gia
khang
huyet
thanh
bai
lift
Tinh
djc
hifu
khang
huyet
<65.000 cho thii nghiem xac dinh
hifu
gia vie xin thanh phim
>8.000 cho thu nghifm xac dinh
tac
nhan ngoai lai
<8.000 cho
thii
nghiem xac dinh
hifu
gia
vie
xin thanh phim
>16.000 cho thir nghifm
xac
dinh
tac nhan ngoai lai
<16.000 cho thu nghifm
xac
dinh
hifu
gia vac xin thanh phim
Cheo typ 2, 3 ; <32
Cheo vdi
typ 1,3: <16
Cheo vdi typ
1,2
: <32
2.3.Tieu
chuan
Dac hieu bing
thir nghifm
nhan dang qua
ky
thuat
miln dich huynh quang
Tif
u chuan co sd
Vdtrung
> 6.400
>
1.000.000
>100.000
>
1.000.000
> 100.000
Dac hieu bang thir nghiem
nhan dang qua
ky
thuat miln
dich huynh quang
3.
So
Iirgng va
chat
lu-gng
huylt
thanh
san xuat
a.l.Khing
25,5
134
Hifu
gia
4.096
8.192
4.096
4.096
Huyet thanh < 4.000
Dat TC Co sd
The tich
35
42,0
51,0
128
Hieu
gia
3.072
1.536
1.536
Khdng dat
Thf tich
20,0
46,5
38,5
105
Hifu gia
96,0
256
512
38
42
80
45
45
259
(22,78%)
6.144
8.192
6.144
41
35
37
45
41
35
40
274
30
25
50
46
45
42
40
50
328
730
(64,21%)
2.048
xuit dgt 3. Hifu gia khang huyft thanh tir
Idn
hon
1000 don vi sg sir dung cho
thii
nghifm trung hda me gat don phat hien tac nhan ngdai
lai.
Trong dgt
1 san
xuit huylt thanh, 3 thd cd khang huyet thanh
hifu
gia thip
nSn
khdng
sii dyng
dugc, 7/10 cd khang huyet thanh cao hon dugc su dung. So vdi khang
huylt thanh
Nhjt
ban cung cip (hifu gia >4000 don vi) thi trong dgt
1
chi
4/10
thd dat
yeu ciu(l,2,4,7) hifu gia huylt thanh tir 4096-8.192; nhu vay chi 134/327ml huylt
14
thanh
san
xuat cd hifu gia khang huylt thanh tuong
duong
vdi
ngoai.
Nhu vay khang huylt thanh Sdi dugc san xuit,
hifu
gia dat tieu chuin Nhat ban
chilm
22,78%; Huylt thanh dat hieu gia tieu chuin co sd
64,21%
va
13,01%
lugng
huyft thanh thap khdng dat tieu chuin co sd qui dinh.
Khang
huygt
thanh Sdi dugc dung cho cac thd nghifm
kim
dinh vacxin thanh
pham (Chuan
dd
hifu gia
va
dn dinh nhift
;Thii
nghifm nhan dang);kifm dinh vacxin
ban thanh
pham(Chuin
dg hifu gia
va
dn dinh
nhift;Thii
nghiem tac
Idn
khi
san
xuit 7,5 trifu lilu vie xin.
Vif c
cSn
thiet phai
thiSt lap
qui trinh san xuat khang huyet thanh Sdi cd hieu gia cao
va
dong deu tren thd sir dung. Hifn nay
POLYVAC
dang
thilt
lap qui trinh san xuit
khang nguyen vk chgn
Igc
thd de dat dugc ket qua nhu
y
mudn.
3.2.
Khing
huyet thanh
B^i
liet
Huyet
thanh
B?i
lift
typ
c$ng
1
2
3
4
5
7
9
10
8
tho
2
3
4
6
7
8
9
7
thd
11
12
14
16
17
21
23
7
thd
29
262144
65536
131072
65536
131072
512
2048
8192
2048
2048
512
512
16384
16384
4096
2048
2048
64
512
x
X
X
X
Cheo
typ 2
tai
ty
If
pha
loang
71
X
Cheo
typ 3
X
X
Cheo
typ 3
X
140
X
X
X
X
Cheo
typ 2
127,5ml
338,5
Ket qua san xuit huylt thanh Bai lift typ
1
tren 8 thd vdi tdng huylt thanh thu
duoc 276 ml vdi hifu gia rit cao.5/8 thd cd hieu gia khang
thi
cao nhit,
thi
tich huylt
thanh 170ml su dung cho thu nghifm trung hda me gat don, hf sd pha loang
tii
256-
2048 lan, vdi ty
hem
nhung rit dac
hifu
du tieu chuin su dung cho
thii nghifm
xac dinh hieu gia
vie
xin Bai het tam lien vdi ndng do
1
don vi /ml.
Hifu gia khang
thi
typ
3
san xuit tren 7 thd, mac
dii
hifu gia khang
thi typ3
cao
hon hifu gia khang
thi
typ 2 nhung
vin
thip hon
hifu
gia khang
thi
typ
1
rit nhilu.
dung cho
thii
nghifm tac
nhan ngoai lai bing phuong phap trung hda hoan toan me gat don. 122
ml
khang
thi
bi
lo?i
bd vi khdng dac hifu
typ;
khang the cdn lai su dung cho thir
nghifm
tim hieu gia
trong
vie
xin thanh phim vdi
sir
dung
1
don vi /ml.
Ciing qua ket qua tren khang the Bai lift typ
1
rit cao, cao hon rat nhilu so vdi
khang the Bai lift typ 2 va 3 can nghien
ciiu
san xuit khang the typ 2, 3 sao cho hifu
gia cao nhu
typl
de
6
18
8
22
13
20
24
25
TSng
cOng
G1P8
G1P8
G1P8
G1P8
G1P8
G1P8
G1P8
G1P8
G1P8
Wa
Wa
DSl
DSl
RRV
RRV
RRVmix
RRVmix
42
44
35
30
26
56
34
26
60
40
32
72
24
17
41
974
102400
102400
25.600
102400
6.400
102.400
25.600
25.600
6.400
1.638.400
1.638.400
409.600
409.600
1.638.400
1.638.400
1.638.400
409.600
RRV mix
(61,5ml)
Hifu
gia huylt thanh Rota
sdn
xuit
tii
5 chiing deu cho hieu gia rat cao thap nhat
chiing G1P8 (6.400)
Hifu
gia huylt thanh Rota
san
xuat tir chiing hoang dai cao hon chung giam ddc
lyre
rit nhilu, hifu gia chiing G1P8 giam dgc
lire
chi bang
'A
den 1/16 chung
hoang dai
Huylt thanh san xuit tit chung RRV dugc ling dung tdt trong thir nghifm tun
hifu gia
vie
xin Rota vi
hhih
anh
kit
qua r6 net va dep; Huylt thanh
tii
nhiing
TiSm Ik
1
ng4y
0; TiSm 2,5ml
h5n
djch virut + 2,5
ml ti
chit FCA;
Tifim
trong da
nhi^u
vj tri,
0,1
mI/1
vi tri;
TiSm
lan 2 ngiy 7: Tiem 5 ml virut Soi khdng c6
ti
chit; TiSm
vio
dudi da
diii
2
bSn,
m5i bSn
2,5 ml;
Tiem lan 3
ngiy
14'
TiSm 5 ml virut Soi khdng c6 ta chit; Tiem
Chuan
d$
hifu gia, xac dinh dg dac hifu
Chia nhd va bao quan
Qui trinh
san
xuat huyet thanh Bai
lift
San xuat khang nguyen tren te bao vera
Tinh sach khang nguyen va pha khang nguyen vdi nong do 10 CCID/0,lml
Gay dap
irng
mien djch tren thd sir dung ta dugc
Thd dugc each ly
tii
7-10 ngay, gay
dap ung
miln dich 6 lan tiem
each
nhau 2 tuan vao
ngay:
0:14:28:42:56:70;
84.
Lich va Ulu
tiem cu
thi:
TiSm lin
i ngiy
0: TiSm 0,2ml virut Bai liet + 0,2ml ta
dupe
co
diii
2 bSn, mdi ben 0,5 ml;
TiSm lin 5
ng4y
56: TiSm 1ml virut Bai
liSt
+ 1ml ti duoc FCA; TiSm vao co
diii
2 ben, mdi ben 0,5 ml;
TiSra lin
6 tlgiy
70: TiSm 1ml virut Bai
liSt
+
Iml
ta duoc FCA; TiSm
v&o
co
diii
2 bSn, mdi ben 0,5 ml;
Lay mau, tach huyet thanh
Lay mau
toan bd cudi
cimg vao
ngay 84 sau lin tiem 1
Chuan dg hifu gia, xac dinh dg dac hifu
Chia nhd va bao quan
• Qui trinh san xuat huyft thanh Rota
San xuat khang nguyen
Rota + 1ml ti
dirijc
FCA; Tiem
v4o
ca
diii
2 ben, m5i
b8n
0,5 ml;
TiSm lin 3
ngiy
28: TiSm 1ml virut Rota + 1ml
ti dtrpc
FCA; TiSm vio co
diii
2
bdn,
m6i
ben 0,5 ml;
Tifim
lin 4 ngiy 42: TiSm 1ml virut Rota + 1ml ta
du(7c
FCA; Tiem
vio
ca
diii
2 ben,
m6i
ben 0,5 ml;
Lay man, tach huyet thanh
dung dugc trong
kiem dinh vie xin Sdi.
Huyet thanh Bai lift
Sd lugng
thi
tich khdng huylt thanh Bai lift
typ
1, 2, 3 thu dugc
743
ml (276 ml
huylt thanh typ 1, 227ml huylt thanh Bai lift typ 2 va 240,5ml huylt thanh Bai lift
typs 3) trong dd hifu gia dat
va
cao hon khang huylt thanh chuin ciia Nhat Ban la
283ml chu
ylu
la huylt thanh typ l(170ml), khang huyet thanh
niy sii
dvmg cho thir
nghifm tac nhan ngoai lai bing phuong phap trung hda hoan toan me gat don. 122 ml
khang huylt thanh bi loai bd vi khdng dac
hifu
typ;
khang huylt thanh cdn lai
sii dimg
cho
thu:
nghifm
tim hieu gid trong
vie
gia
vac
xin Rota
vi hinh
dnh kit
qua ro net va dep; Huyet thanh
tii
nhiing chiing khac su dung cho thir
nghifm dimg ky thu$t ELISA.
3.
Khang huylt thanh da dugc thi nghifm img dung kiem tra trong thii nghifm
tac nhan
ngo?i
lai,
thii nghifm
nhan dang, thir
nghifm xac
dinh
hifu
gia vac xin, trong
ky
thu|t
ELISA so vdi
mlu
khang huylt thanh nhap ngoai cho ket qua tot, thay
thi
dugc khang huylt thanh
nh|p
ngoai
KIENNGHI
Bai
bao
va dao
tao
Bai
bao
da dang:
01
bai
Nghien
ciiu
san xuat huylt thanh Sdi
sii
dung cho
Idem
dinh vac xin.Tap Chi Y
hgc
dvr
phong,
2008, Tap
XVIH
sd 6(98), tr.74-78
Dio
tgio:
01
thacsy
Ten de
tai:
Nghien
ciiu
tlich va
tinh khang nguyen 2
1.1.2.
Cac yeu to anh
hudug din
tinh sinh miln dich 2
1.1.2.1. Nhiing tinh chat cua ban than khang nguyen anh hudng den tinh sinh mien
dich 2
1.1.2.2.
Nhung tinh chat cua he thong sinh hoc anh hudng den tinh sinh mien dich 4
1.1.2.3.
Quylt
dinh khang nguyen 7
1.1.2.4.
Khang nguyen vi sinh vat 7
1.2.
BChang
huylt thanh 8
1.2.1.Cau
tnic
CO
ban cua khang huylt thanh 9
1.2.2.
Cac quyet dinh khang nguyen tren phan tir globulin miln dich
11
1.2.3.
Cac l(5p
khang huylt thanh 13
1.2.4.
Ciu true
bao
tham gia
vao
dap img mien djch
t^o
khang huyet thanh 23
1.3.4.
Ta
chat, nguyen ly tac
dyng
cua ta chit 24
1.3.5.
Co chl
hinh
thanh
khing
huylt thanh 24
1.4. Khdng nguyen virut 24
1.4.1.VirutSdi
24
1.4.1.1.
Ciu
talc 24
1.4.1.2.
Qua trinh
iMn
len cua vinit Sdi 26
1.4.1.3.
Dap ung mien dich 27
1.4.2.
1.4.3.3. Hinh
thdi
va ciu true 34
1.4.3.4.
cac
thanh phin hoa hpc cua vuut Rcta
va chiic
nang 34
1.4.3.5.
Phan nhdmva typ
huylt thanh 35
1.4.3.6.
Tmh chat hoa ly 36
1.4.3.7.
Nuoi
ciy
._.
37
1.4.3.8.
Sv
nhan len cua virat Rota trong tl bao 37
1.5.
Thd 39
l.S.l.DSctinhsmhhpccuathd
39
1.5.2.
Cac loai thd dugc nuoi va sir
dung
tai
nude
2.1.2.
Nguyen vat
Ufu
va phuong phap san xuit khang nguyen Bai Het 46
2.1.3.
Nguy6n vdt
lieu va phuong phap san xuit khang nguyen Rota 47
2.2.
Nguyen vat
lifu
va phuong phap san xuit khang huylt thanh 48
2.2.1.
Nguyen vat lifu
va
phuong phap san xuit khang huylt thanh Sdi 48
2.2.2. Nguyen vit lifu vk phuong phap san xuit khang huylt thanh Bai lift 51
2.2.3.
Nguyen
vkt
lifu
va
phuong phap
san
xuit khang huylt thanh Rota 52
2.3.
xac
dinh hifu gia khang huylt thanh 52
2.3.1.
Xac dinh
hifu
62
2.4.2. Cdc budc tiln hdnh 63
2.4.2.1.
Chuan bi
Ing thii
63
2.4.2.2. Tiln hdnh thir 63
2.4.2.3.
Dpc
kit
qud 64
2.4.2.4. Ddnh gid
kit
qua 64
2.5.
iTng
dung khang huyet thanh trong kiem dinh vac xin 65
2.5.1.
xac
dinh vuut ngoai lai (khdng huyet thanh Sdi, khdng huyet thanh Bai
Hft)
65
2.5.2. Xac dinh tinh ddc hifu, hieu gid cua virat Rota
bSng
phuong phap miln dich
huynh quang (dp dung cho khdng huyet thanh Rota) 65
2.5.2.1.
Nguyen
vdt Hfu
nghien
1
74
3.2.3.
Ket qua hieu gia khang huyet thanh lan 2 gay dap ung mien dich 76
3.2.4. Ket
qua
hieu gia khang huyet thanh lan
3
gay dap ung mien dich 77
3.2.5.
Tinh
hinh
sir dung khang huyet thanh Soi 78
3.3.
Kit qua san xult
khang huylt thanh Bai het 80
3.3.1.
S^
xuit khang huylt thanh Bai liet typl 81
3.3.2. Ket qua san
xuSt Idiang huySt
thanh Bai het typ 2 85
3.3.3.
Kit
qua hieu gia khang huylt thanh Bai Het typ
3
90
3.3.4. Ung dung trung hoa hoan toan me gat don 94
3.4.
Kit