Nghiên cứu chọn chủng ứng cử vắc xin phòng bệnh tay, chân, miệng do virus ev71

DOI: 10.31276/VJST.64( 12).29-33 Khoa hoc Y - Diipc I Y hoc dtf phdng T Nghien cun chon chung uug cir vac-xin phong benh tay, chan, mieng virus EV71 Nguyen Thj Yen Nhi12, Vo Trin Ngoc Trinh1, Pham Le Qu6c Hirng3, Nguy§n Thj Hanh Lan1, Hoang Ngoc Khanh Quynh1, Le Thj Lien1, Le Ha Tam Duong1, Cao Thj Bao Van1,4* lien P a steu r TP H o C hi M inh Truong Dai hoc Khoa hoc Tu nhien D hoc Q uoc g ia TP H o C hi M inh 'Trung tam Kiem soat B enh tat TP H o C hi M inh 4Hen Cong nghe Y dupe Van Cao N g a y n h a n b a i /3 /2 2 ; n g a y c h u y e n phan bien 25/3/2022; nhan phan b ie n 18 2 ; n g a y c h i p n h an d a n g /4 /2 2 Tom tat: N ghien cm i dune thirc hien nham chon lira chung irng cir cho v ife nghien evu va s in s u i t v ic -x in phdng benh tay, chan, m ieng (TC M ) virus EV71 tai V iet N am Dir lieu giam sat viras EV71 hang nam cua M en Pasteur TP Ho C hi M inh tir nam 2003 den 2013 da dupe sir dung d£ d u doan xu hirdrog ties boa Trinh tu viing gen VP1 cua 100 chung EV71 cua V iet N am tir G enB ank d u o c sir dung de danh gia dp turong d6og tai mpt so epitope va tim cac truth tu bien nhat K et qua, chung EV71 kieu gen phu B5 m ang ten B5-203P-2013 da dope cbpn Trai qna qaa trinh thich un g va chon dong dun tren te bao Vero cua chung B5-203P-2013, B5-203P-2013-P10.1 d i dope chpo t u i chung ting cir cho vac-xin EV71 voi on djnh di truyen va dat hieu gia 108 TCID^m l cho d ip la g k h iog th i traog hoa cheo v o i cac kieu gen phu khac n h u B 5, C4, C5 Tit khoa: chung umg cir EV 71, dap irng khang the trung hoa cheo, kieu gen phu, thich ung tren te bao Veto Chi so phan loai: 3.3 B i t van Be H a n Q u o c V a c -x in c u a T ru n g Q u o c d a d u g c th u o n g m B e n h T C M la m o t b e n h t r u y e n n h i e m p h o b i e n a h o a n h u n g c h i d u g c s u d u n g tr o n g n o i d ja n u d e n a y [3 ], M o t tr e e m , n h a t l a tr e d u o i t u o i [ ] B e n h d o m o t n h o m E n t e r o v ir u s t h u o c h o P i c o m a v i r i d a e g a y T r o n g d o , v i r u s E V d u p e q u a n ta m n h ie u n h a t d o c h u n g c o th e g a y c a c b e n h c a n h n a n g , k e m t h e o b i e n c h u n g t h a n k in h , t i m , p h o i v a t h a m c h i d a n d e n tir v o n g [ ], 9 , d i c h E V b u n g p h a t v a la n r o n g t a i k h u v u c A t r e n d a c d i e m c u a c a c c h u n g v i r u s l u u h a n h ta i t u n g k h u v u c , d i e n h in h n h u c h u n g C a d a d u g c sir d u n g d T r u n g Q u o c ; c h u n g B v a B t u o n g u m g d u g c sir d u n g d S i n g a p o r e v a D a i L o a n [4 ] H ie u q u a b a o v e c u a c h u n g d o i v o i c a c c h u n g lu u h a n h ta i V i e t N a m h a u n h u c h u a d u g c g h i n h a n T r o n g V ir u s E V la n d a u t i e n d u g c g h i n h a n v a o n a m N am d a c d i e m c h u n g c u a c a c v a c - x i n n a y l a d u g c p h a t tr ie n d u a k h i d o , d a c d i e m v e d j e h t e h g c p h a n t u c u a v i r u s E V ta i V ie t N a m c o n h ie u d ie m k h a c b ie t, c a c k ie u g e n E V d a - T h a i B i n h D u o n g S ir lu u h a n h n o i t r o i v a ta i n o i d u g c g h i n h a n la i la C l , C , C v a B [ ] D o d o , c h u n g t r o i, d a d a n g v e k i e u g e n c u a E V d a g a y c a c tr a n d i c h to i tie n h a n h n g h ie n c u u c h p n lg c c h u n g E V u n g c u v a v d i q u y m o k h a c n h a u t r o n g k h u v u c T a i V i e t N a m , v ir u s ta o n g a n h a n g c h iin g c h o v ie c n g h ie n c u u sa n x u a t v a c -x in E V d u g c p h a n la p la n d a u t i e n v a o n a m 0 T ir d o , p h d n g b e n h T C M d o v i r u s E V d u a tr e n c h u n g d a i d ie n n h i e u d g t d i c h T C M l d n , n h o c o l i e n q u a n d e n l o a i v ir u s n a y c h o c a c c h u n g d a n g lu u h a n h ta i V ie t N a m l i e n t i e p x a y r a tir n a m 0 d e n vori h a n g c h u c n g a n V a t lieu va phuting phap nghien cu(U chau c a n h ie m v a it n h a t tr u d n g h g p tu v o n g Vat lieu H i e n n a y , b e n h T C M v a n c h u a c o t h u o c d i e u tr i, v a c - x i n C h u n g v ir u s : d a n g la c h ie n lu g e to t n h a t d e k ie m s o a t d je h b e n h N h ie u lo a i v a c - x in p h o n g T C M d a v a d a n g d u g c p h a t tr ie n , tu y n h ie n n h d n h u n g u u th e n h u tin h a n to a n c a o , k h a n a n g m ie n d je h to t v a c o th e d u g c p h a t tr ie n n h a n h h o n n h d v a o v ie c th a m k h a o c a c c o n g n g h e h ie n c o , c h i c o v a c - x in to a n p h a n la p t a i V i e n P a s t e u r T P H o C h i M i n h , m o t s o c h u n g d u n g N g h i e n c u u la m s a n g c u a D a i h g c O x f o r d ( O U C R U ) Te bao: am 64( 12) 12.2022 V ir u s E V d u g c n u o i c a y tr e n d o n g t e b a o V e r o (E C A A C N o 8 ) *Tac g i a lie n h e: E m a il: v a n c a o p a s te u r ia g m a il.c o m K H O A HOC CONG NGHE (B ) t r o n g d a n h g i a d a p u n g m i e n d i c h c h e o d u g c n h a n tir D o n v i b a t h o a t d a n g d u g c n g h i e n c u u v a t h u n g h i e m la m s a n g ta i c a c q u o c g i a v a v i i n g la n h t h o n h u D a i L o a n , S in g a p o r e , C h u n g r in g c u c h o v a c - x i n E V v a c h u n g d e d a n h g ia p h a n u n g m ie n d ic h c h e o d u g c p h a n 29 Khoa hoc Y - DUOc I Y hoc dU phdng c a c k ie u g e n p h u B , C l , C v a C lu u h a n h ta i c a c v u n g d ia Selection o f candidate strains for hand, foot and m outh disease vaccine against enterovirus 71 T h i Y en N h i N g u y e n 1’2, T n N g o c T rin h V o1, L e Q u o c H u n g P h a m 3, T h i H a n h L a n N g u y e n 1, N g o c K h a n h Q u y n h H o a n g 1, T h i L ie n L e 1, H a T a m D u o n g L e 1, T h i B a o V an C a o 1,4* 'P asteur Institute in H o Chi M inh city 2University o f Science, Vietnam N ational University, H o Chi M inh city 3H o Chi M inh city Center fo r D isease Control a nd Prevention 4Vancao M edipharm Technology Institute l y k h a c n h a u c u a V ie t N a m tir n a m 0 d e n tir G e n B a n k P h a n m e m B io E d it d u g c s u d u n g d e s o s a n h c a c tr in h t u tu o m g d o n g d e n h a n d ie n c a c k ie u h in h tu c m g d o n g c a o ta i c a c v j tri e p it o p e q u a n tr g n g C h u n g c o s u tu c m g d o n g c a o n h a t v d i c a c c h u n g k h a c ta i c a c v i tri n a y m a n g c a c v u n g q u y e t d in h k h a n g n g u y e n p h o b ie n n h a t d u g c c h g n la m c h u n g u n g c u T h ic h lin g c h u n g v iru s tre n te b a o Vero vd c h o n d o n g dcm c h u n g th ic h u n g : Q u a tr in h th ic h u n g d u g c t h u c h ie n t h o n g q u a v i e c c a y c h u y e n a d o p h a lo a n g th a p q u a n h ie u d d i c a y c h u y e n n h a m c h g n lg c d u g c c a c c h u n g t h ic h n g h i v d i t e b a o V e r o C a c m l u s a u c a c d d i c a y c h u y e n d u g c k ie m tra h ie u g i a T C I D 50, n h u n g m a u c h o h ie u g ia to t t ie p tu c d u g c c h g n l g c c h o d e n k h i c h u n g c o k h a n a n g p h a t tr ie n t o t tr e n t e b a o V e r o t a i m a t d o g a y R e c e iv e d 21 M arch 02 ; a ccep ted 21 A p ril 2 n h ie m th a p v a c o h ie u g i a c a o (tr e n T C I D 50/m l) T a i d d i c a y Abstract: c h u y e n c u o i c im g , c a c d o n g d cm c u a c h u n g s e d u g c c h g n lg c The study aim ed to select candidate strains from V ietnam for the developm ent o f the hand, foot and m outh disease (H FM D ) vaccine against enterovirus 71 (E V 71) A nnual EV71 virus surveillance data o f P asteur Institute in Ho C hi M inh city from 2003 to 2013 w as used to predict evolutionary trends O ne hundred VP1 sequences o f V ietnam strains from the G enB ank database w ere used to evaluate the identity o f acid am in sequences and identify the consensus sequences at key epitopes A s a result, the subgenogroup B5 strain nam ed B 5-203P-2013 was selected T he strain w as adapted on Vero cells by m ultiple passages and plaque isolated T he strain B5-203P-2013-P10.1 w as selected as a candidate strain for the HFMD vaccine due to possessing genetic stability, high titer o f 108 T C ID S0/m l and cross-neutralising antibody responses against other subgenogroups B5, C4, C5 Keywords: adaptation on Vero cells, cross-neutralising antibody responses, subgenogroup EV71 candidate t h o n g q u a k y th u a t ta o p la q u e K ie m tra tln h o n d in h d i tru y en c u a c h u n g th ic h u n g d a th ic h n g h i: T r in h t u g e n V P tr e n c h u n g u n g c u b a n d a u v a sa u k h i t h ic h u n g d u g c k h u e c h d a i b a n g p h u c m g p h a p R T -P C R v d i c a p m o i d a c h ie u v a g ia i tr in h t u t h e o p h u o n g p h a p S a n g e r C a c trin h t u g e n m u c t ie u s a u d o d u g c x ir l y , la p rap n h d s u h o tr g c u a p h a n m e m C L C M a in W o r k b e n c h 5 v a B io E d it K ie m tra tln h sin h m ie n d ic h c h eo : C h u n g v ir u s s a u k h i d u g c t h ic h n g h i v a c h g n l g c d u g c n u o i c a y t a n g s in h tr e n te b a o V e r o , d ic h v ir u s s a u d o d u g c th u h o a c h , tin h c h e v a b a t h o a t to o th a n h k h a n g n g u y e n C h u o t n h a t tr a n g c h u n g B a lb /c ( B i o L A S C O T a iw a n C o , L td ) 6-8 tu a n tu o i (5 c o n ) d u g c t ie m li e u k h a n g n g u y e n h a m l u g n g p g p h o i tr o n v d i ta c h a t n h o m ( A lh y d r o g e l ) ta i c a c th d i d ie m tu a n t h u n h a t v a t h u tu C h u o t d u g c th u m a u v a o tu a n t h u 8, m a u d u g c ta c h h u y e t th a n h d e t ie n h a n h d a n h g ia m ie n d ic h c h e o v d i c a c c h u n g C , C , B q u a p h a n u n g tr u n g h o a strain, P h a n u n g tr u n g h o a x a c d in h h ie u g ia k h a n g t h e tr u n g h o a v ir u s c u a c a c m a u h u y e t th a n h c h u o t C a c m a u h u y e t th a n h c h u o t d u g c p h a lo a n g b a c Classification number: 3.1 t u d o p h a lo a n g 1/10 b a n d a u v a u v d i 0 T C I D 50 v ir u s c a c c h u n g C , C , B tr e n c a c d ia g i e n g t u o n g u n g d a d u g c c a y te b a o V e r o m a t d o x l t e b a o / g i e n g g i d tr a d e d o , u d d ie u k ie n ° C v a % C 2, g h i n h a n Dia diem vd thifi gian nghien ciiu d a u h ie u h u y h o a i te b a o ( c y t o p h a y o g e n ic e f f e c t ) s a u n g a y N g h ie n c m i d u g c th u c h ie n ta i P h o n g T h i n g h ie m s in h h o c d a o c u a d o p h a lo a n g th a p n h a t k h o n g g h i n h a n d a u h ie u h u y g a y n h ie m H i e u g i a k h a n g th e tr a n g h o a d u g c tin h la n g h ic h pfcan tu K h o a V i s in h m ie n d ic h , V ie n P a s te u r T P H o C h i M in h i r o n s d k ri g ia n tir n a m d e n h o a i te b ao K i t qua va ban luan Pkmntg phap nghien ciru Chon chung bang phan tick dir lieu dich te hoc phan tir P fa m n c h x u h u c m g tie n h o d vd so s a n k trin h tu : o n N g h ie n s i t d u n g d u lie u g ia m sa t E V h a n g n a m d o i v d i v ir u s EVT cm te c c m D u li e u p h a n ric h x u h u d n g t i e n h o a c u a c a c c h u n g E V ta i V ie t N a m t u n a m 0 d e n c h o th a y , c o s u c h u y e n M e n P a s te u r T P H o C h i M in h li e n tu c tr o n g k h o a n g d ic h s u lu u h a n h c u a k ie u g e n C s a n g k ie u g e n B , tr o n g d o n r n a m 0 d e n n h a m d a n h g ia s u t h a y d o i c a c d in h d ie m c u a s u h ie n d ie n k ie u g e n C la n a m 1 N a m f e t e a e n d e c h o n k ie u g e n d a i d ie n T ie p t h e o , c h u n g t o i sur 2 c h u n g C v a n c h ie m u u t h e n h u n g c o s u x u a t h ie n v a dkag d f t i t e Uriah n r \ u n g th a y th e d a n c u a c h u n g B t u n a m 1 (h in h ) C h o d e n n a m g e n V P c u a 0 c h u n g E V th u o c 12-2022 30 Khoa hoc Y - Difctc I Y hoc du phong , c h u n g B d a c h ie m m i th e v a g a n n h u h o a n to a n th a y T r o n g v u n g e p it o p e - , v i tri d u g c x e m la c o li e n th e c h u n g C V d i x u h u d n g d o , c h u n g to i c h o n n h u n g c h u n g q u a n d e n d o c tin h c u a v ir u s d a y c h u n g t o i c h o n c h u n g m a n g m a n g k ie u g e n B d e p h a n t ic h tr in h t u n h a m c h o n d u g c a x it g lu t a m ic ta i v i tri n a y d o d a i d ie n c h o p h a n ld n c h u n g B c h u n g u n g cur c h o v a c - x i n E V v a h a u h e t c a c c h u n g C , C D o t b ie n t h a y t h e g l y c i n e (G ) hoac g lu t a m in e ( Q ) th a n h a x it g lu t a m ic ( E ) ta i v j tri a x it a m in tren V P l d o c la p h o a c k e t h o p v d i s u t h a y d o i c a c a x it amin khac c h ju tr a c h n h ie m c h o s u t h ic h n g h i v a d o c l u c c h o sir lav nhiem tr e n c h u o t [7 ] CJ n g u d i , d o t b ie n V P - E Q d a dugc tim thay tr o n g c a c t r a d n g h o p n h ie m E V n a n g H em nua R Li va cs ( 1 ) [8 ] c u n g d a b a o c a o v e c a c d o t b ie n khac co lien quan d e n t y le lu u h a n h h em t r o n g c a c t r a d n g h o p nang cua EV71 nhu V P - G / Q / R Vdi epitope vung a x it a m in - 5 , v j tri m a n g a x it glutamic (E) d cac chung B5 d u g c h in h th a n h d u d i a p l u c c h g n loc duong cua cac chung B5 lu u h a n h ta i V ie t N a m [9 ] , C a c chung d kieu gen C deu mang l y s i n e (K) d v j tri n a y Hinh Phan bo kieu gen phu cua virus EV71 theo thdi gian V d i m u c t i e u ta o v a c - x i n c o ti'nh s in h m i e n d jc h v d i c a c c h u n g E V d a n g v a s e lu u h a n h tr o n g t u o n g la i g a n , c h u n g to i t ie n h a n h p h a n t i c h s u tu o m g d o n g g i u a c a c v u n g e p it o p e q u a n tr o n g tr e n tr in h t u g e n V P l c u a m o t s o k ie u g e n p h u E V Vdi vung epitope 163-177 chung to i g h i n h a n c o s u b a o toan cao giua cac chung kieu gen phu v d i n h a u D i e u n a y tuemg t u vdi mot so phat hien trade day la co su bao toan cao g i u a cac kieu gen phu cung kieu gen va cac kieu gen vdi nhau, chi co chung nguyen thuy BiCr (kieu gen A) la co s u k h a c biet ve axit amin tai vj tri 167 va 172 [10], C a c v u n g c h u a e p it o p e q u a n tr o n g tr e n p h a n t u V P l d u g c b ie t Q u a v i e c s o s a n h tr in h t u v a t im v u n g b a o to n d c a c v j d e n h ie n n a y b a o g o m tit a x it a m in - 5 , - , - 7 tri e p it o p e , c h u n g t o i d a c h o n c h u n g B ( G e n e B a n k va -2 K U 8 ) la m chung u n g cu C co te n g o i B - P - d u g c p h a n la p t u b e n h n h i c o tr ie u c h u n g T C M trinh tu phan tich m u c d o B d T ie n G i a n g n a m C h u n g n a y m a n g c a c v u n g e p it o p e p h o b ie n c h o p h a n ld n c h u n g B cu n g n h u cac ch u n g C l, C v a C Thich nghi chung tren te bao Vero va chon dong d m chung thich ung va muc xam chung to su thich u n g d a n c u a c h u n g tr e n t e b a o V e r o D o p h a loang cua cac ddi c a y s a u th a p horn d d i c a y t r a d e c h o d e n k h i dat su on djnh Sau la n c a y c h u y e n , c h u n g c h g n l g c c h o h ie u gia cao nhat vdi T C I D 50 d a t ~ T I C D 50/ m l s o v d i T C I D 50/ m l cua ldn c iv K e t q u a c a y c h u y e n c h o th a y h ie u g ia n h ie m t e b a o c u a c h u n g c h g n l g c ta n g d a n Hinh So sanh trinh tu> tai cac vj tri epitop cua cac chung EV71 nghien cum K hi t ie n hanh phan t ic h tr in h tu gen VPl g iu a d a u t i e n ( b a n g 1) Bang Hieu gia cua chung B5-203P-2013 qua cac dori thich dng khac cac c h u n g E V d u a v a o n g h ie n c u u , c h u n g t o i p h a t h ie n v u n g So ddi thi'ch irng D q pha loang Hieu gi £ virus thu i h y t ( I C B y h ^ c o m ir e d o b a o td n io -2 103-2 c a o v a g i o n g n h a u 0 % d h a u h e t c a c c h u n g v d i tr in h t u io -3 103-2 Y P T F G E H K Q E K D L E Y G A C ( h in h ) D a y la m o t tr o n g c a c 10-4 104 ' 10-5 10* 10-6 10* 1041 10 10* HF e p it o p e tr u n g h o a ta i v j tri - 2 v u n g e p it o p e tr u n g h o a q u a n tr p n g v a d u g c s u d u n g p h o b ie n tr o n g c a c n g h i e n c u u v a c - x i n p e p t it c h o n g la i v ir u s E V C a c n g h ie n c u u t r a d e d a y c h o th a y , h u y e t th a n h k h a n g S P d u g c td n g h g p t u d o a n p e p t it - 2 ( Y P T F G E H K Q E K D L E Y ) g iu p b a o v e - % c h u o t s o s i n h n h ie m c a c c h u n g E V m a n g k ie u g e n C , C , B , B v a B ta i h ie u g i a k h a n g t h l tr u n g h o a :3 [6 ] 10* w 10 * w TAP CHI 64(12) 12.2022 31 Khoa hoc Y - Di/dc I Y hoc du phdng T c a c d d i c a y th u v a , h i e u g i a v ir u s th u d u g c d a t I n v i t r o g e n ( h i n h B ) K e t q u a p h a n t i c h c h o t h a y , tr in h c a o n h a t sa u g id g a y n h ie m k h i c a c te b a o d a b i h u y h o a i tu g e n V P g a n n h ir h o a n t o a n ( h i n h ) - P 1 ) tu o m g d o n g 0 % s o veri m a u v ir u s b a n d a u cu a m a u sa u dcri c a y c h u y e n ( B - P - ( B - P - ) (h in h ) Enterovirus A71 strain B5-230P-2O13 >Ae»Mm.~nenOwnB 2013-05-01 capsid protein VP1 gene, partial cds sequence to K U M Z9 4ai »i M v e im t l runqei- 1*o891 3t>Sy » i n- iK s KKUia _ _ _ _ _ _ _ _ _ _ _ km biatm: Query S b je t Query 61 S b jc t 61 Query li «KA’C(iALIAC>AC 129 ri,*«Xitt*rc&Acr«^( 120 K166IUM' T(^MUCTCLM6*.'6 S6yct 121 Query 111 SbjCT 1*1 W U ' l ' W CUlOlKA11* ICOAA! A t! 40! OAT CtJUaUiC'ClMfat'fat'MtfurUafabMAIlAltMArACtMiHiAi U U U U ' X r >MCtlAC«CM'6CAbUKi*b6CUK.U.Ib 2«« ’,66C'CAC6CA0'ACA0CA66C»ACCACCCUi 240 (A) Hinh Thu nhan gen VP1 cua chung chon loc (A) Gen VP1 d u g c khudeh dai qua phan ung PCR; (B) So sanh trinh tu gen VP1 Hinh Ket qua gay nhiem cua chung (mg ctr (A, B, C) Te bao bi huy hoai sau 48, 72 va 96 gib gay nhiim; (D) Hinh anh cua chung B5-203P-2013-P10.1 sau thich ung cong tren te bao Vero virus EV71 dich nuoi cSy dirge chup dirbi kinh hien vi dien tCr truyen suot (vi tri mui ten) N h u v a y , g e n V P c u a c h u n g B - P - - P 1 h o a n t o a n o n d in h k h i t h i c h u n g t r e n t e b a o V e r o S a u d b i c a y c h u y e n , c h u n g d a d a t d u g c d o o n d in h v e h ie u g ia c u n g n h u d a t d u g c h ie u g ia ta n g s in h d u c a o T ir k e t q u a tr e n , c h u n g B - P - - P d u g c c h g n c h o v ie c sa n x u a t v a c -x in , c h u n g to i tie n h a n h n u o i c a y ta o d e t a n g s i n h la m n g a n h a n g c h u n g s a n x u a t d o d a t h i e u g i a p l a q u e c h o c h u n g d e c h p n d o n g d em b a n g p h u e m g p h a p t a n g s i n h t o t v a o n d in h d i t r u y e n tr e n v u n g g e n V P P la q u e a s s a y (h in h ) P la q u e m a n g k y h i e u B -2 P - K lta n a n g tr u n g Ito a c h e o c u a c h u n g u n g c i t - P 1 d u g c c h g n s a n x u a t d o d a t d u g c h i e u g i a tr e n 8T C I D 50/ m l B e k i e m tra k h a n a n g c h o d a p u n g m i e n d j e h c h e o c u a c h u n g B - P - - P 1 , c h u n g t o i c h g n d a i d i e n c u a c a c k i e u g e n k h a c n h a u d a trrn g lu u h a n h ta i V i e t N a m n h u C l , C , C v a B d e d a n h g ia K e t q u a b a n g c h o t h a y , k h a n a n g tr u n g h o a c u a h u y e t th a n h v d i c a c k i e u g e n k h a c n h a u d e u d a t m ere tr e n H i e n t a i, v a n c h u a c o s u t h o n g n h a t m u c k h a n g t h e tr u n g h o a c a n t h i e t d n g u d i la b a o n h i e u , t u y n h i e n d c h u o t , m u c k h a n g t h e t r u n g h o a c a n c a o horn B a y l a m u c k h a n g th e to i th ie u b a o v e c h u o t s o s in h tr o n g c a c th i n g h ie m th u t h a c h v d i m o h in h m i e n d i c h th u d o n g tr e n c h u o t [ ] N h u - in h K§t qua tao plaque dcri cay thu 10 Gi§ng la doi v a y , h u y e t t h a n h tir c h u o t n h a t tr a n g d u g c t i e m v a c - x i n B - rr-urtg te bao; gidng 2, 3, 4, 5, tuong ung cac nong pha loang P - - P 1 c o t h e c h o d a p u n g m i e n d j e h c h e o v d i :4a irus \ 10-2, 3, 10'4 va 10‘5 cac ch u n g E V 71 khac bao g o m C 4, C va B , m ac du kha \ ;e c c h g n c h u n g b a n g p h u o n g p h a p p la q u e a s s a y d a d u g c n h i e u n h o m n g h i e n c u u u n g d u n g t r o n g v i e c c h o n - c h u n g t h u a n c o k h a n a n g t a n g s in h t o t d a t h i c h n g h i - -i t h o n g n u o i c a y q u a q u a tr in h c h g n l g c [ 1 , S ir o n d in h d i tr u y e n tr e n g e n V P ~ Bang Kha nang dap img mien dich cheo cua the khang the 5-203P-2013-P10.1 ] Chung virus Trung binh nhan hieu gia khang the trung hoa (GMT) 5-203P -2013-P 10.1 (chung vSc-xin) 243 E V 71/B V N -1 (2014) 160 E V 71/C 4-11 ( l l ) 211 E V 71/C V N 3 -I8 (2018) 184 EV71/C 5-11 (2011) 139 c e n \ ' P tr e n c h u n g B - P - b a n d a u v a i - ir n g t h a n h c o n g B - P - - P » dugc phuonng p h a p R T -P C R v o i c a p m o i d a c tte s L - i : e n d i ' a n p h a m k h u e c h d a i tr e n g e l a g a r o s e c i'it t r i ; ’ n a n g tr u n g h o a c h u n g C k e m hern s o v d i B v a C a % * _ i : h :e n n o t v a c h c o k i c h t h u d e t u o u g u n g ~c r c h u a n (1 K b P lu s D N A L a d d e r , >A12) 12-2Q22 ■ 32 Khoa hoc Y - Dittic I Y hoc du phong C a c d o t b i e n v a t a i t o h o p th ir d n g x u y e n x a y r a t r o n g q u a V i e n P a s t e u r T P H o C h i M i n h v a B o m v j N g h i e n c u u la m tr in h t i e n h o a c u a v i r u s E V , d o d o v i e c p h a n r in g c h e o c o s a n g c u a B a i h o c O x fo r d (O U C R U ) C a c ta c g ia x in c h a n t h e c h o n g la i n h i e u l o a i v i r u s E V k h a c n h a u la m o t c h i e n t h a n h c a m om l u g e q u a n t r o n g t r o n g d i n h h ir d n g p h a t t r i e n v a c - x i n P h a n u n g k h a n g t h e t r u n g h o a d u g c x e m la m o t c h i s o q u a n t r o n g t r o n g d a p r in g m i e n d i c h v d i E V , t h u d n g d u g c sir d u n g d e d a n h g ia h ie u q u a c u a v a c -x in M o t tr o n g n h u n g tie u c h i d a n h g i a h i e u q u a c u a m o t v a c - x i n E V la k h a n g t h e tju li£i t im [ 1] J Zhao, et al (2016), “Age patterns and transmission characteristics o f hand, foot and mouth disease in China”, B M C In fe c t D is , 16(1), DOI: 10.1186 s i2879-016-2008-y [2] P Chong, et al (2015) "Review of enterovirus 71 vaccines”, C lin pp.797-803 d u g c ta o c o k h a n a n g tr u n g h o a c a c c h u n g th u o c n h o m g e n k h a c V a o n a m 2 , T o c h ir c Y t e T h e g i d i ( W H O ) d a nUa In fe c t D is ( ) b a n h a n h c a c k h u y e n n g h i v e c h a t lu g n g , a n to a n v a h ie u [3] M.L Li et al (2021), “Enterovirus A71 vaccines”, V accines DOI: 10.3390/vaccines9030199 q u a c u a v a c - x in E V b a t h o a t T r o n g d o c o m o t d ie u q u a n ( B a s e l / (3 ) t r g n g n o i b a t la c a n n g h i e n c r iu k h a n a n g c h o p h a n r in g [4] S Esposito, N Principi (2018), “Hand, foot and mouth disease: Current knowledge on clinical manifestations, epidemiology, aetiology and prevention”, E ar J C lin M ic ro b io l In fe c t D is , 37(3), pp.391-398 c h e o c u a k h a n g t h e t r u n g h o a d o v a c - x i n t a o [ ] , M o t s o n g h i e n c u u d a ta p t r u n g v a o t i m h i e u t i n h k h a n g n g u y e n c u a c a c c h u n g E V N g h ie n c u u c u a K M iz u ta v a c s ( 0 ) [ ] c h o t h a y , k i e u g e n B k i c h h o a t d u g c k h a n g t h e tr u n g h oa ch o phan un g ch eo vd i cac ch u n g B , B , B , C l, C v a C m a n h h o n k h a n g th e c u a k ie u g e n C G d n d a y n h lt , n g h i e n c u u c u a P L i u v a c s ( 2 ) [ ] v § k h a n g t h i t r u n g h o a d u g c t a o r a tir k i i u g e n A , B - B , C , C v a C d u g c x a c d in h c o k h a n a n g t r u n g h o a c h e o v d i c h i n h n h u n g c h u n g n a y K e t q u a c h o th a y , c a c k il u g e n A , B v a C d i u ta o k h a n g th e c o k h a n a n g tr u n g h o a v d i c a c n h o m k ie u g e n k h a c T u y n h i e n c o s u k h a c n h a u v e m ure d o t r u n g h o a d c a c k ie u g e n T a i V ie t N a m , s a u k h i th a y th e c h u n g C v a o n a m , c h u n g B lu u h a n h rai rac tr o n g c o n g d o n g c h o d e n n a m t h i c h u n g C q u a y tr d la i c h i e m u u t h e v a c h u n g B d u g c g h i n h a n i r a c [1 ] T u y n h ie n , tr o n g m o t n g h ie n c u u d a n h g ia k h a n g th e tr u n g h o a d c a c b e n h n h a n T C M V ie t N a m , k h a n g th e c u a n h u n g b e n h n h a n n h ie m c h u n g B lu u h a n h t r o n g g i a i d o a n - ta i V i e t N a m c h o t h a y k h a n a n g tr u n g h o a v d i c h u n g C c u a n a m v a k h o n g c o s u k h a c b ie t v d i k h a n a n g tr u n g h o a v d i c h in h c h u n g B [1 ] , C o th e n h a n th a y d d a y la c a c k ie u g e n p h u c u a E V c o t h e x u a t h i e n m a n g t in h c h u k y n e n v i e c g i a m s a t d e c h g n c h u n g d a i d ie n p h u h g p v a c o p h a n u n g c h e o v d i n h ie u k ie u g e n p h u k h a c n h a u l a d i e u q u a n tr g n g Ket m an T r i v i e c p h a n t i c h x u h u d n g t i e n h o a v a p h a n t i c h tr in h tu t u o n g d o n g c u a c a c e p it o p e tr o n g v u n g g e n V P , q u a q u a tr in h t h i c h u n g v a c h g n d o n g d o n tr e n t e b a o V e r o , c h u n g t o i d a th u d u g c c h u n g m a n g E V c o k i e u g e n p h u B m a n g te n -2 P -2 - P 1 la m chung u n g cri c h o [5] J.L Geoghegan, et al (2015), “Phylodynamics o f enterovirus A71-associated hand, foot, and mouth disease in Viet Nam”, J Virol 89(17), pp.8871-8879 [6] D.G Foo, et al (2007), “Identification o f neutralizing linear epitopes from the VP1 capsid protein of enterovirus 71 using synthetic peptides”, V irus R e s , 125(1), pp.61-68 [7] M Arita, et al (2008), “Cooperative effect of the attenuation determinants derived from poliovirus sabin strain is essential for attenuation o f enterovirus 71 in the NOD/SCID mouse infection model" J V irol , 82(4), pp 1787-1797 [8] R Li, et al (2011), “Molecular analysis of virulent determinants o f enterovirus 71”, P L O S O N E , 6(10), DOI: 10.1371/joumal.pone.0026237 [9] N.T.T Thao, et al (2017), “Evolution and spatiotemporal dynamics of enterovirus A71 subgenogroups in Vietnam”, J In fe c t D i s 216(11), pp.1371-1379 [10] P Liu, et al (2021), “Cross-antigenicity between EV71 sub-genotypes: Implications for vaccine efficacy”, V iruses, (5 ) D O L 10.3390/vl 3050720 [11] Y.F Tseng, et al (2011), “Adaptation o f h ig h - g ro w th influenza H5N1 vaccine virus in Vero cells: Implications f o r p a n d e m ic preparedness”, P L O S O N E , 6(10), DOI: 10.1371/joumal.pone.0024057 [12] N.S Ogando, et al (2020), “SARS-coronavirus-2 re p lic a tio n in Vero E6 cells: Replication kinetics, rapid adaptation and c y to p a th o lo g Y - J G en Virol., 1 (9 ), pp.925-940 [13] C K Yu, et al (2000), “Neutralizing antibody provided p ro te c tio n against enterovirus type 71 lethal challenge in neonatal mice” J B i o m e d S e t , 7(6), pp.523-528 [14] D Lei, et al (2020), “WHO working group m e e tin g k » d c w i n p WHO recommendations to assure the quality, sa fety a n d td h eaem n ff enterovirus 71 vaccines”, V accine, (3 ) p p -4 v a c -x in E V C h u n g n a y c o tin h o n d jn h d i tr u y e n s o v d i c h u n g g o c b a n d a u v a c h o k h a n a n g t a n g s i n h t o t tr e n t e b a o V e r o v d i h i e u g i a T C I D 50/ m l B o n g t h d i c o k h a n a n g tr u n g h o a c h e o v d i c a c k ie u g e n p h u k h a c lu u h a n h ta i V ie t N a m n h u B , C va C Mil CAM 0N [15] K Mizuta, et al (2009), “ C ro ss -a n tig e ro c ity am o n g E V ?In n m » from different genogroups isolated in Y am agataL Japan.hm nnan M t a i 2007”, V accine, 27(24), pp.3153-3158 [16] L.N.T Nhan, et al (2018k “Sevae cmnmanmA d i amndmod hand, foot and mouth disease V ie tn a m 3tU t (trim m er nqpmmf an impending outbreak” E u m s u m e iUnmt r ZSHNl BOfc M 2H W 15M 7917.ES.2018.23.46.1800590 [17] L A N g u y e t e t aL C h i m g s u d u n g t r o n g n g h i e n c u u d u g c p h a n la p , d in h d a n h v a c u n g c a p b d i P h o n g X e t n g h i e m v i r u s d u r in g r u o t, S ng ng he Viet Nam 64(12) 12.2022 enteroviruses in p a tie n ts w ith hm d I In fe c t D is (2 ) p p -3 33 ... developm ent o f the hand, foot and m outh disease (H FM D ) vaccine against enterovirus 71 (E V 71) A nnual EV71 virus surveillance data o f P asteur Institute in Ho C hi M inh city from 2003 to... Chung virus Trung binh nhan hieu gia khang the trung hoa (GMT) 5-203P -2013-P 10.1 (chung vSc -xin) 243 E V 71/B V N -1 (2014) 160 E V 71/C 4-11 ( l l ) 211 E V 71/C V N 3 -I8 (2018) 184 EV71/ C... o r p a n d e m ic preparedness”, P L O S O N E , 6(10), DOI: 10.1371/joumal.pone.0024057 [12] N.S Ogando, et al (2020), “SARS-coronavirus-2 re p lic a tio n in Vero E6 cells: Replication kinetics,