1. 1
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Malyala
.
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.
.
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***
* * * Microparticles
19.1
. cosal
.
.
[ 1]
- .
( (
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quence
.M
. 94608 Emeryville 4560
com.singh novartis.Manmohan @ :
(.ed) .Vajdy M
2008 +
499
2
500
.M Malyala .P
.[3]
- subcu
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immu .
nization

2. .
.
- .
- mercially
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.
19.2
- ( ) ( )
.[4]
- Fõ .
. cused
- )
(
ribosylating -ADP
secre
.
63LTK )
63LTK .[5] (72LTR
ribosyltransferase -ADP
1 ) 72LTR
.[5] (
.[5]
.
-
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.
3
19
501
.[6])
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[9]) ([8] moniae
.
.[8])
.
Protollin 31 -
.[10 9]
TLR .

3. .
immunostimulatory (ODN)oligodinucleotides -
.
(9TLR) 9
nuclease ODNs - .[11] 12) (6)
phosphorothioate
ODNs - .
ODNs
.[11]
9TLR 1Th
amebia .[11]
.
( ) inhibitable galactosamine - / histolytica
.[11]ODN -
ODN - herence
. 1Th ducer
1Th
.[11]
KLKL 31IC
5
a1immunostimulatory oligodeoxynucleotide ODN KLK
- stim .1Th 9TLR
a1ODN 31IC ulatory
9TLR
proinflammatory
1Th IFN 9TLR .[12] 1Th
9TLR
9TLR [12]
(pDCs)plasmacytoid dosomal
TLRs 4TLR
9TLR .[12]
4
502
.M Malyala .P
9TLR
.[12]
- IFN + 8CD
- poten .[12] nationci
immunomodulator 31IC 9TLR
31IC .
KLKL
5
KLK

4. . ( )
6- - B85Ag
HBHA
KLKL .[12]
5
KLK
transfection
.[12])
- .
31 - 6 - - B85Ag
31IC 6 - - B85Ag .[12]
+ 4CD
. - IFN
Proteosomes Protollin
- Protollin .LPS
(rHA) ( )
250
IFN [10]
splenocytes
rHA -Protollin .5 -
Protollin strating
.[13] (19.2)
bioadhesive
.
19.3
Bioadhesive 19.3.1
bioadhesion 1980
bioadhesive .[14]
mucoadhesion .
5
19
503
Mucoadhesion .
.[14]
mucoadhesion
.
bioadhesive
- epithe
bioadhesive .[14]lium
methacrylic chitosans

5. mucopolysaccharide [15]
- . - glucuronic
ification
HYAFF .[16]HYAFF
.[17] coacervation
bioadhesive HYAFF
.[17 15]
HYAFF
.
- bioad
hesive microsphere
( )
.63LTK
bioadhesive +
.(19.2 19.1 .Figs) microsphere
bioadhesive microsphere
.
0
500
1000
1500
2000
2500
42
56
63LTK +
HYAFF + + 63LTK
19.1 .
( )
63LTK
.(HYAFF + + 63LTK ) HYAFF bioadhesive
(+ HYAFF ) ( )
-- / + ( ) .(63LTK + )
6
504
.M Malyala .P
0
400
800
1200
1600
63LTK + +HYAFF
+ + 63LTK

6. HYAFF
19.2 .
( ) ( ) hemagglutination
+ ) esiveHYAFF bioadh 63LTK
( ) .(HYAFF + 63LTK
.(63LTK + ) (+ HYAFF )
bioadhesive
([18] excipient
.[18]
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.[19] /
. bioadhesive
- deliv 'bioadhesion'
ery
.
bioadhesive
():
( ) ( )
. ()
.
.
PL G M icroparticles 19.3.2
-
scine
- attrac .(PLG) (glycolide -lactide )
PLG
resorbable
( 1 ~) [22 21 20] .
( )
[24 23] . ( )
7
19
505
PLG
[26 25] .
.
.[27] ( )
LGP
[28] . [28]

7. ) microparticle ( )
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45-20 ( divinylbenzene lammonium
.[29]
IFN .
6-2- 4-
.( ) 1Th
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1-
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b11CD
+
. / PLG
b11CD
( ) ( )
.[30] [29] ( )
[31]
/ - PLG
b11CD
+
[31]
.
1- / PLG
.[32]hybridoma
Microparticles PLG 19.3.2.1
.
. munization
8
506
.M Malyala .P
.
PLG
[35 34 33]
[39 38 37 36] Bordetella
- immu .[41] typhimurium ([40]

8. nization
- .[42]intravaginal
croparticles
.[43] terotoxin
.[44]
- deliv
.[46 45] ery
.[47] (oMALT)
- deliv
.[48]ery
[49 13]
.[50]
.
- underes
.timated
.[13]
Niosomal L iposomal 19.3.3
liposomal
Liposomal .
- ] .
somes
.
.[51]
niosomes ( )
- . ( )
amphiphilic
.[52]
Liposomal
.
.
9
19
507
. Somroop
( )
pilus (LPS) 1lipopolysaccharide O
(rTcpA)
.[51] ODN -
( )
.
) própria
(
. 13 6

9. TcpA - - LPS 4
19.1 . 3
.[51] . 3
.
.[53] ( )
monomthoxy tresyl
MVAIIIB) (TMPEG)
-- /
. - poxvirus (
PEGylation
liposome/TMPEG-gal- / MVAIIIB
- .
-
/ BALB temic
deliv poxvirus
Niosomes Mannosylated .[53] (19.1) eries
( )
palmitoyl .[54 13]
( ) 19.1
[55 53 51]
-
750
--
/
2200
--
--
4 ( )
--
10

10. 1 O .V + )
+ LPS
(TcpA
. ODN
--
72
31
--
64
--
10
508
.M Malyala .P
- Niosomes Mannosylated 19.2
Protollin
[54 12]
/
1.78
Niosomes /
56.23
Mannosylated /
Niosome
1000
/ /

11. 20
//
24
/ Protollin / /
3397
- . Peyer ( )
( )
.[54] (19.2) -
ODN -
-
. Tafaghodi
.[55]
munoreactivity
- .
(0.001)
.(19.1)
ODN -
(0.05> )
. lavages (0.01> )
.
.
) . .[55]
- ODNs (
.
ODNs
ODNs sponses
.[56] /
19.4 ‫ﺟ‬
.
.
11
19
509
.
.
.[59 58 57] geting
.[61 60]
.

12. . Nelle Cronen .
‫ﺟ‬
.37 257 . . . . 1989 .Y Ghendon .1
249 1983 Riddiough .2
.3189
.25 4 .rev .Epidemiol 1982 Glezen .3
.98 53 .J . 2000 .T .4
.4276 67 . 1999 Hagan'O .G Barackman .5
and ,.R ,Rappuoli ,.G ,Douce ,.G ,Dougan ,.V ,Giannelli ,.G ,Del Giudice ,MM ,Giuliani .6
.1123 ,187 ,.Med .Exp .J ,1998 .M ,Pizza
,.R ,Rappuoli ,.M ,Pizza ,.D ,Hagan'O ,.H ,Stewart ,GA ,Murphy ,.E ,McNeela ,EJ ,Ryan .7
.6270 ,67 ,.Immun .Infect ,1999KH ,and Mills
.I ,d Jonsdottiran ,CA ,Siegrist ,.M ,Moreau ,.G ,Del Giudice ,.S ,Bjarnarson ,.H ,Jakobsen .8
.1443 ,70 ,.Immun .Infect ,2002
.559 ,6 ,Vaccines .Expert Rev ,2007JD ,and Hayball ,MP ,Brown ,KR ,Diener ,CK ,Fraser .9
,Vaccine ,2004DS ,and Burt ,GH ,Lowell ,.N ,Bellerose ,.F ,Allard ,.S ,Cyr ,.T ,Jones .10
.3691 ,22
.4917 ,75 ,.Immun .Infect ,2007 .K ,and Chadee ,CP ,Ivory .11
,Lingnau ,.C ,Kritsch ,.A ,Williams ,.G ,Hatch ,AW ,Olsen ,.I ,Rosenkrands ,EM ,Agger .12
,.K
.5452 ,24 ,Vaccine ,2006 .P ,and Andersen ,KS ,Korsholm ,CS ,Andersen ,.A ,von Gabain
.183 ,14 ,.Sci . .J .Eur ,2001DJ ,Brayden .13
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.J ,1994 .L ,and Benedetti ,.M ,Miglietta ,.L ,Gill ,AN ,Fisher ,NF ,Farraj ,.l ,Illum .15
Controlled
.133 ,29 ,easeRel
,1998FW ,and David ,.A ,Giovanni ,.B ,Paola ,.R ,Marco ,.D ,Partrick ,.C ,Davide .16
-Biomate
.2101 ,19 ,rials
and ,.L ,Callegaro ,.L ,Bacella ,.L ,Rochira ,.M ,Miglietta ,.P ,Ramires ,.J ,Richardson .17
.9 ,115 ,Pharm .J .Int ,1995 .L ,Benedetti
,16 ,Vaccine ,1998 .L ,and Illum ,SS ,Davis ,.R ,Rappuoli ,AN ,Fisher ,.I ,Gill-Jabbal .18
.2039
Drug .Adv ,2001SS ,and Davis ,AN ,Fisher ,.M ,Hinchcliffe ,.I ,Gill-Jabbal ,.L ,Illum .19
.Deliv
.81 ,51 ,.Rev
.269 ,2 ,Expert Review Vaccines ,2003 .M ,and Singh ,.D ,Hagan'O .20
.1 ,12 ,.Drug Carrier Syst .Ther .Rev .Crit ,1995 .H ,and Toguchi ,.H ,Okada .21
published erratum appears in Nat] 16 ,.Biotechnol .Nat ,1998PA ,and Burke ,SD ,Putney .22
.153 ,[478:(5)16;May 1998Biotechnol
.661 ,81 ,Immunology ,1994AM ,and Mowat ,DT ,Hagan'O ,AM ,Donachie ,KJ ,Maloy .23