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immunostimulatory                              (ODN)oligodinucleotides -

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.                    (      )
                 6-         - B85Ag
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mucopolysaccharide                        [15]
-              .           -                glucuronic
                    ...
HYAFF

                                                                              19.2 .
(   )                         ...
) microparticle                                                                 ( )
                -            benzyltri...
nization
                    -                                                           .[42]intravaginal
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TcpA -     - LPS                           4
                                             19.1 .                    3
    ...
1 O .V + )
                                              + LPS
                                              (TcpA


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20
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.                          Nelle Cronen                    .
                                                             ...
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  1. 1. 1 19 Malyala . iscoms .( ) . . .mucosally . mucosally *** * * * Microparticles 19.1 . cosal . . [ 1] - . ( ( - .[2] quence .M . 94608 Emeryville 4560 com.singh novartis.Manmohan @ : (.ed) .Vajdy M 2008 + 499 2 500 .M Malyala .P .[3] - subcu - . taneous immu . nization
  2. 2. . . - . - mercially . cines . 19.2 - ( ) ( ) .[4] - Fõ . . cused - ) ( ribosylating -ADP secre . 63LTK ) 63LTK .[5] (72LTR ribosyltransferase -ADP 1 ) 72LTR .[5] ( .[5] . - . intravaginal . 3 19 501 .[6]) - pneu .S [7]) .B [9]) ([8] moniae . .[8]) . Protollin 31 - .[10 9] TLR .
  3. 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. 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. 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. 6. HYAFF 19.2 . ( ) ( ) hemagglutination + ) esiveHYAFF bioadh 63LTK ( ) .(HYAFF + 63LTK .(63LTK + ) (+ HYAFF ) bioadhesive ([18] excipient .[18] - immunomodula .[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. 7. ) microparticle ( ) - benzyltrimety solfinate 45-20 ( divinylbenzene lammonium .[29] IFN . 6-2- 4- .( ) 1Th - phenotyp PLG - -1- ically PLG . temic 1- - immunos .( ) - (NCL) ( taining 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. 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. 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. 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. 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. 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 .660 ,11 ,Vaccine ,1993 .L ,and Illum ,.S ,Wharton ,.D ,Rafferty ,DT ,Hagan'O .14 .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

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