Novel Vaccines for Defense Against Pneumonic Plague

download Novel Vaccines for Defense Against Pneumonic Plague

of 43

Transcript of Novel Vaccines for Defense Against Pneumonic Plague

  • 7/22/2019 Novel Vaccines for Defense Against Pneumonic Plague

    1/43

    Kcscl Tcoomk`s dfr E`d`ks`

    Cacmkst Zk`unfkmo Zlcau`

    E`v`ke`r Huncr

    33-33-9:33

  • 7/22/2019 Novel Vaccines for Defense Against Pneumonic Plague

    2/43

    Cohkfwl`ea`n`kts

    N`tza`r Lci2

    Er. E`kkms N`tza`r

    Er. Amrmsg Hmrmnckb`swcrc

    Er. H``r _uk

    Nmog`ll` Qylcke-F'Irm`k

    _gcrfk _clnfk

    _gckkck Rml`s

    Yfi`rts _`ck

    Mnnukflfay Ofr`2

    Er. @enuke Afss`lmk

    ]mlm Lmk

    E`pcrtn`kt fd Og`nmocl cke Imflfamocl

    @kamk``rmka2

    Er. Iclcbm Kcrcsmngck

    Er. Ir`t Plr`y

    E`pcrtn`kt fd T`t`rmkcry Nmorfimflfay cke

    Zr`v`ktmv` N`emomk`2

    Er. Nmogc`l B. Qckk`nu`gl`r

    Er. Cnckec @. Ycn`r-Ucmt

    E`pcrtn`kt fd Nmorfimflfay cke

    Mnnukflfay 2

    Er. K`bct @amln`z

  • 7/22/2019 Novel Vaccines for Defense Against Pneumonic Plague

    3/43

    Qfrlewme` e`ctgs drfn nuofscl mkd`otmfks

  • 7/22/2019 Novel Vaccines for Defense Against Pneumonic Plague

    4/43

    Qgy mktrckcscl mnnukmzctmfk6

    Kcscl pcssca` ms ncbfr pfrtcl fd`ktry dfr luka pctgfa`ks

    A`k`rct` nuofscl cke syst`nmo

    mnnukmty A`k`rct`s mnnukmty ct ftg`rnuofscl surdco`s

    Mnnuk` r`spfks`s foour ctpctgfa`k-`ktry smt`

    Zr`v`kts mkd`otmfks

    @cs` fd cenmkmstrctmfk/Ncssvcoomkctmfk

  • 7/22/2019 Novel Vaccines for Defense Against Pneumonic Plague

    5/43

  • 7/22/2019 Novel Vaccines for Defense Against Pneumonic Plague

    6/43

    Icot`rmflfay ]`rsmkmc p`stms

    ]`rsmkmc p`stms Cktmquc

    ]`rsmkmc p`stms N`em`vclms

    ]`rsmkmc p`stms Frm`ktclms

    3-9n x :.0n, smkal` o`ll fr sgfrt ogcmk

    Arcn-k`actmv`, Impflcr stcmkmka

    Dcoultctmv` ckc`rfi`

    Kfknftml`, kfkspfrulctmka

    Octclcs`+, fxmecs`-, ur`cs`-

    Cil` tf arfw 5-5:O, fptmnun 97 O

    Dlfooulckt arfwtg mk irftg

    Ar`y-wgmt` trcksluo`kt oflfkm`s fk Ilffe

    Cacr. Drm`e `aa cpp`crcko` mk fle`r

    oflfkm`s fk IC

    Mnc `s2 K] _tct` E` crtn`kt fd G`cltg-Qceswfrtg O`kt`r, ZGML-OEO

  • 7/22/2019 Novel Vaccines for Defense Against Pneumonic Plague

    7/43

    Lor

    1:hi

    T Ca

    Y`smstcko` tf pgcafoytfsms

    _urvmvcl mk ncorfpgca`

    ]fps

    Zgcafoytfsms

    Zlct`l`t caar`actmfkMkdlnnctfry r`spfks`

    pDrc

    33:hi

    D3 Ca

    Cktmpgcafoytmo

    Zst

    =.0hi

    Zlc

    E`arce` dmirmk

    & ftg`r `xtrco`llulcrprft`mks

    LZ_

    EMO

    @keftfxmo sgfoh

    Tmrul`ko` Dcotfrs

    Ceg`smks

  • 7/22/2019 Novel Vaccines for Defense Against Pneumonic Plague

    8/43

    Ug` Alficl Emstrmiutmfk fd Zlcau`

    Drfn2 Zlcau`2 Zcst, Zr`s`kt, cke Du tur`_t`ks`tg KO, Ctsgcicr II, I`af k N, I`lncmk _Y, I`rtg`rct @, t cl. ZLf_ N`emomk ` Tfl. 0, Kf. 3, ? efm23:.3?13/bfurk cl.pn`e.::0:::?

    http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0050003http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0050003
  • 7/22/2019 Novel Vaccines for Defense Against Pneumonic Plague

    9/43

    _ynptfns

    gttp2//`k.wmhmp`emc.fra/wmhm/Ps`r2Nmhc`lVGaastrn/Emcarcns

  • 7/22/2019 Novel Vaccines for Defense Against Pneumonic Plague

    10/43

    Zlcau` Zctgfa`k`sms

    Gunck

    Nmo`

    Gunck

    Kfrncl Luka Mkd`ot`e lukas

    Nmo`

  • 7/22/2019 Novel Vaccines for Defense Against Pneumonic Plague

    11/43

    Zfssmil` Cmrifrk` Urcksnmssmfk Zctgwcys fd ]. p`stms

    cdt`r Mts Mkt`ktmfkcl C`rfsfl Y`l`cs`

    N`tza`r Lci, 9:3:8 gttp2//www.fp`kolmpcrt.fra/

    3::-0:: ODP

    G Z Z m Zl 6

  • 7/22/2019 Novel Vaccines for Defense Against Pneumonic Plague

    12/43

    Gfw tf Zr`v`kt Zk`unfkmo Zlcau`6

    Kckfpcrtmol`sQgfl`-hmll`e O`lls _fluil` Cas Nmorfpcrtmol`s

    Kcturcl imf-pcrtmol`s

    Imfnmn`tmo

    Nultmpl` crrcys fd Ca

    Cssurcko` fd mkcotmvmty

    rD3-Tp3:

    rLsrI

    rCml

    rNclIr]cpN

    rD3-Tp3:

    Ofktrfll`e r`l`cs`

    _mkal`-efs`

    Lfka-t`rn prft`otmfkImfe`arcecil`

    Nfemdmcil` tf sumt Ca r`l`cs`

    Tcoomk`s

    Cebuv

    ckts

    Mkt`rl`uhmk-39 Nfkfpgfspgfryl Lmpme C

    ULY-5 cafkmst

    _cd`

    Kfk-tfxmo

    Ca pr`s`ktctmfk

    @kgcko`s o`llulcr

    cke gunfrcl mnnukmty

    _cd` iy m.k. rfut`

    @stcilmsg`e `ddmocoy

  • 7/22/2019 Novel Vaccines for Defense Against Pneumonic Plague

    13/43

    Mkcotmvct`e ]`rsmkmc p`stms OF=9

    Tcoomk` (m]p)

  • 7/22/2019 Novel Vaccines for Defense Against Pneumonic Plague

    14/43

    Ug` m.k. Zrmn`-Iffst cke Ogcll`ka` _trct`ay dfr

    m]p Tcoomk`

    Ecy : m.k. m]p + ML-39 / m]p/ ZI_

    Ecy 93 m.k. m]p + ML-39 / m]p/ ZI_

    Ecy 7: m.k. ]. p`stms OF=9

    Ecy =5 @ke fd survmvcl stuey

  • 7/22/2019 Novel Vaccines for Defense Against Pneumonic Plague

    15/43

    Cenmkmstrctmfk fd m.k. m]p + ML-39 ms _cd`

    cke Q`ll-Ufl`rct`e

    : 9 5 4 7 3: 39=:

    =0

    3::

    *

    Z

  • 7/22/2019 Novel Vaccines for Defense Against Pneumonic Plague

    16/43

    Cenmkmstrctmfk fd m.k. m]p + ML-39 Zrft`ot`e

    cacmkst Zrmncry Zk`unfkmo Zlcau`

    : 0 3: 30 9: 90:

    90

    0:

    10

    3::

    3:1m]p+ML-39

    3:1m]p

    ZI_

    ks

    **

    Z>:.::3

    7.0 x 3:9

    ODP, m.k.

    Ecys pfst-ogcll`ka`

    ICLI/o nmo`.

    Z`ro`kts

    urvmvcl

    C.

    I.

    Ecys : 93 7:

    3. 3:1

    m]p + :.0a ML-39

    9. 3:1

    m]p

    ?. ZI_

    ICLI/o nmo`,M.k. vcoomkctmfk

    Zrmnmka Iffstmka

    =5

    ]. p`stmsOF=9ogcllcka`, m.k.,

    7.03:9ODP@ke fd survmvcl

    fis`rvctmfk

  • 7/22/2019 Novel Vaccines for Defense Against Pneumonic Plague

    17/43

    ML-39 @kgcko`e tg` Zrfeuotmfk fd Cktm-]. p`stms

    Cktmifem`s

    : 3: 9: ?: 5: 0:3

    9

    ?

    5

    0

    *** *** ***

    Z :.:5

    Ecy ?0, pfst-vcoomkctmfk

    CktmifeyUmt`rs(lfa3:

    )

    C. I. O.

  • 7/22/2019 Novel Vaccines for Defense Against Pneumonic Plague

    18/43

    Ug` m]p + ML-39 Zrmn`-Iffst iy m.k. Yfut`

    Zr`v`kt`e Zulnfkcry Oflfkmzctmfk fd ]. p`stms

  • 7/22/2019 Novel Vaccines for Defense Against Pneumonic Plague

    19/43

    Ug` m.k. m]p + ML-39 Zrmn`-Iffst Mkeuo`e O`llulcr

    Caar`actmfks mk Zulnfkcry Zcr`kogync

    m]p + ML-39 ZI_

    Ecy?0

    pfst-vcoomkctmfk

    C.

    I.

    Ecy97

    pfst-vcoomkctmfk

    I99: I99:

    Ug m m] ML 39 Z m I Z e

  • 7/22/2019 Novel Vaccines for Defense Against Pneumonic Plague

    20/43

    19gpfst-ogc

    ll`ka`

    m]p + ML-39 ZI_

    Ug` m.k. m]p + ML-39 Zrmn`-Iffst Zr`v`kt`e

    E`v`lfpn`kt fd Zulnfkcry Zctgflfay

    Ug` m k m]p + ML 39 Zrmn` Iffst Zr`v`kt`e E`v`lfpn`kt fd

  • 7/22/2019 Novel Vaccines for Defense Against Pneumonic Plague

    21/43

    Ug` m.k. m]p + ML-39 Zrmn`-Iffst Zr`v`kt`e E`v`lfpn`kt fdZulnfkcry Zctgflfay

    Ug` m k m]p + ML 39 Zrmn` Iffst Mkeuo`e Zrft`otmfk ms

  • 7/22/2019 Novel Vaccines for Defense Against Pneumonic Plague

    22/43

    Ug` m.k. m]p + ML-39 Zrmn`-Iffst Mkeuo`e Zrft`otmfk msCssfomct`e wmtg Lfw`r L`v`ls fd Zulnfkcry Oytfhmk`s Cdt`r

    m.k. Ogcll`ka`ML-4

    m]p + ML-39 ZI_ Pkmkd`ot`e:

    3

    9

    ?

    5

    0*** ***

    Z< :.::3 Z< :.::3

    pa/nl(lfa3:)

    ML-3:

    m]p + ML-39 ZI_ Pkmkd`ot`e:.7

    :.=

    3.:

    3.3

    3.9 m]p + ML-39

    ZI_

    Pkmkd`ot`e

    ks

    pa/nl(lfa3:)

    NOZ-3

    m]p + ML-39 ZI_ Pkmkd`ot`e:

    3

    9

    ?

    5 ** *Z< :.:3 Z< :.:0

    pa/nl(lfa3:)

    MDK-

    m]p + ML-39 ZI_ Pkmkd`ot`e:

    3

    9

    ? ***Z< :.:3 Z< :.:0

    pa/nl(lfa3:)

    UKD-

    m]p + ML-39 ZI_ Pkmkd`ot`e:

    3

    9

    ?

    5

    * *Z< :.:0 Z< :.:0

    (pa/nl)lfa3:

    ML-39p1:

    m]p + ML-39 ZI_ Pkmkd`ot`e:.0

    3.:

    3.0

    9.:

    * *Z< :.:0 Z< :.:0

    pa/nl(lfa3:)

    Ug D Y Y m e d C tmi e em t e

  • 7/22/2019 Novel Vaccines for Defense Against Pneumonic Plague

    23/43

    Ug` DoY cr` Y`qumr`e dfr Cktmifey-n`emct`e

    Zcssmv` cke Cotmv` Mnnukmty

    : 0 3: 30:

    90

    0:

    10

    3::

    *Z< :.:5

    Ecys pfst-ogcll`ka`O01IL/4 nmo`

    Z`ro`ktsurvmvcl

    : 0 3: 30:

    90

    0:

    10

    3::

    * Z< :.:9

    Ecys pfst-mkd`otmfkICLI/o nmo`

    Z`ro`ktsurvmv

    cl

    : 0 3: 30

    :

    90

    0:

    10

    3::

    3:1m]p + ML-39 Do Y

    -/-

    ZI_

    3:1m]p + ML-39 Do Y

    +/+

    ks

    *Z< :.:5

    Ecys pfst-mkd`otmfkO01IL/4 nmo`

    Z`ro`ktsurvmvcl

    _ynifl ICLI/o Nmo` Arfup M_ / KN_ trcksd`r (Umn`) Qmle-typ` M_ pr`- cke pfst-ogcll ka` -95, :, +95, cke +57g fd mkd`otmfk

    Qmle-typ` M_ pfst-ogcll`ka` +37g fd mkd`otmfk

    Qmle-typ` KN_ -95, :, +95, cke +57g fd mkd`otmfk

    M_2 Mnnuk` _`run8 KN_2 Kfrncl nfus` s`run

    _ynifl O01IL/4 nmo` Arfup M_/KN_ trcksd`r (Umn`) DoY+/+ M_ pr`- cke pfst-ogcll ka` -95, :, +95, cke +57g fd mkd otmfk

    DoY+/+ KN_ pr`- cke pfst-ogcll`ka -95, :, +95, cke +57g fd mkd otmfk

    DoY-/- M_ pr`- cke pfst-ogcll ka` -95, :, +95, cke +57g fd mkd otmfk

    DoY-/-

    KN_ pr`- cke pfst-ogcll`ka -95, :, +95, cke +57g fd mkd otmfk

    C.

    I.

    O.

  • 7/22/2019 Novel Vaccines for Defense Against Pneumonic Plague

    24/43

    Ug` Ofnpl`n`kt Ef`s Kft Zlcy Yfl` mk

    Zrft`otmfk Eurmka Zcssmv`ly Urcksd`rr`e

    Mnnukmty

    : 0 3: 30:

    90

    0:

    10

    3::

    ks

    Z> :.3?

    Ecys pfst-mkd`otmfkO01IL/4 nmo`

    Z`ro`ktsurv

    mvcl

    _ynifl O01IL/4 nmo` Arfup M_ / KN_ trcksd`r (Umn`)

    O?+/+ M_ pr`- cke pfst-ogcll`ka` -95, :, +95, cke +57g fd mkd`otmfk

    O?-/-

    M_ pr`- cke pfst-ogcll`ka` -95, :, +95, cke +57g fd mkd`otmfk

    O?+/+

    KN_ pr`- cke pfst-ogcll`ka` -95, :, +95, cke +57g fd mkd`otmfk

    O?-/-

    KN_ pr`- cke pfst-ogcll`ka` -95, :, +95, cke +57g fd mkd`otmfk

    Ug` OE5 cke OE7 U O`lls cr` Kft Y`qumr`e dfr Zrft`otmv`

  • 7/22/2019 Novel Vaccines for Defense Against Pneumonic Plague

    25/43

    Ug` OE5 cke OE7 U O`lls cr` Kft Y`qumr`e dfr Zrft`otmv`

    Mnnukmty Ct Umn` fd m.k. Ogcll`ka` Qmtg ]. p`stms

    Ecys

    : 93

    Tcoomkctmfk

    Zrmnmka Iffstmka

    Cktm-nOE5 AH3.5 / Cktm-nOE7 0?-4.19 tr`ctn`kt, m.p.

    1: 1? 14 1= 7?

    7: =:3. 3:1

    m]p + ML-39

    9. 3:1

    m]p + ML-39

    ?. 3:1

    m]p + ML-39

    5. 3:1

    m]p + ML-390. ZI_

    3. 3:1

    m]p + ML-39 (Yct MaA)

    9. 3:1

    m]p + ML-39 (Cktm-OE5)

    ?. 3:1

    m]p + ML-39 (Cktm-OE7)

    5. 3:1

    m]p + ML-39 (Cktm-OE5 + Cktm-OE7)0. ZI_

    ]. p`stms OF=9ogcllcka`, 3::: ODP,m.k.

    @ke fd survmvclfis`rvctmfk

    C.

    I.

    : 0 3::

    90

    0:

    10

    3::

    3:1

    m]p + ML-39 (Yct MaA)

    3:1

    m]p + ML-39 (Cktm-OE5)

    3:1 m]p + ML-39 (Cktm-OE7)

    3:1

    m]p + ML-39 (Cktm-OE5 + Cktm OE7)ZI_ (Pkvcoomkct`e)

    **Z> :.::?

    Ecys pfst-ogcll`ka`ICLI/o nmo`

    Z`ro`ktsurvmvcl

  • 7/22/2019 Novel Vaccines for Defense Against Pneumonic Plague

    26/43

    _unncry

    Zrft`ot cacmkst pk`unfkmo plcau`

    ML-39 ms r`qumr`e dfr mkeuomka prft`otmfk

    Cktmifem`s clfk` ock prfvme` prft`otmfk wgmogms n`emct`e tgrfuag DoY

    U-o`lls cr` emsp`kscil` ct tg` tmn` fd mkd`otmfk

    mk m]p + ML-39 vcoomkct`e nmo`

  • 7/22/2019 Novel Vaccines for Defense Against Pneumonic Plague

    27/43

    _mkal`-Efs` Mktrckcscl

    Zflyckgyerme` Kckfpcrtmol`s dfrTcoomk` E`lmv`ry

    Nct`rmcl Zrfp`rtm`s Fd 0: 0: OZU@A OZG Kckfpcrtmol`s

  • 7/22/2019 Novel Vaccines for Defense Against Pneumonic Plague

    28/43

    Nct`rmcl Zrfp`rtm`s Fd 0:20: OZU@A2OZG Kckfpcrtmol`s

  • 7/22/2019 Novel Vaccines for Defense Against Pneumonic Plague

    29/43

    Tcoomkctmfk Y`amn`k

  • 7/22/2019 Novel Vaccines for Defense Against Pneumonic Plague

    30/43

    _mkal`-Efs` Kckfpcrtmol`s Mkeuo`e Lfka-U rn

    Zrft`otmfk Cacmkst Zk`unfkmo Zlcau`

    4 wh

    9? wh

    Ug` Kckfpcrtmol`s Zr`v`kt`e Oflfkmzctmfk fd ] p`stms cke

  • 7/22/2019 Novel Vaccines for Defense Against Pneumonic Plague

    31/43

    Ug` Kckfpcrtmol`s Zr`v`kt`e Oflfkmzctmfk fd ]. p`stms cke

    Zulnfkcry Gmstfpctgflfay Cdt`r 9? w``hs fd Tcoomkctmfk

    M.k. Tcoomkctmfk fd Kckfpcrtmol`s Zr`v`kt`e pctgflfay fd Fracks Zfst-ogcll`ka`

  • 7/22/2019 Novel Vaccines for Defense Against Pneumonic Plague

    32/43

    p p ay a a

    _mkal` efs` Cenmkmstrctmfk fd Kckfpcrtmol`s Mkeuo`e Lfka

  • 7/22/2019 Novel Vaccines for Defense Against Pneumonic Plague

    33/43

    _mkal`-efs` Cenmkmstrctmfk fd Kckfpcrtmol`s Mkeuo`e Lfka-

    t`rn Cktmifey Umt`rs wmtg Gmag Cvmemty

    _mkal` Efs` Kckfpcrtmol` Zrmnmka Zrft`ot`e

  • 7/22/2019 Novel Vaccines for Defense Against Pneumonic Plague

    34/43

    _mkal`-Efs` Kckfpcrtmol` Zrmnmka Zrft`ot`e

    Nmo` cdt`r 3: Nfktgs

  • 7/22/2019 Novel Vaccines for Defense Against Pneumonic Plague

    35/43

    _unncry

    Zrft`ot cacmkst pk`unfkmo plcau`

    Kckfpcrtmol`s mts`ld cot cs ck cebuvckt

    Kckfpcrtmol`s ock cirfact` tg` k``e dfr

    nultmpl` vcoomkctmfks cke prfvme` lfka-

    eurctmfk mnnukmty

  • 7/22/2019 Novel Vaccines for Defense Against Pneumonic Plague

    36/43

    _mkal`-efs` Mktrckcscl Zfly (lcotmo Come)

    Nmorfspg`r`s dfr Tcoomk` E`lmv`ry

    _m l e : e e m g me

  • 7/22/2019 Novel Vaccines for Defense Against Pneumonic Plague

    37/43

    _mkal`-efs` rD3-Tp3: Lfce`e ZLC Nmorfspg`r`s Zrfvme`s Lfka-

    t`rn Zrft`otmfk Cacmkst Zk`unfkmo Zlcau`

    : 0 3: 30:

    90

    0:

    10

    3::0 a DMT NZ + ML-39 NZ

    1.0 a D3T NZ + ML-39 NZ

    1.0 a D3T NZ

    ZI_*

    Z< :.:?

    *Z< :.:3

    Ecys pfst-mkd`otmfk

    Z`ro`ktsurvmvcl

    34 wh

    ZLC Nm g m e e L Z m C m

  • 7/22/2019 Novel Vaccines for Defense Against Pneumonic Plague

    38/43

    ZLC Nmorfspg`r`s mkeuo`e Lfka-t`rn Zrft`otmfk Cacmkst

    Zk`unfkmo Zlcau` Ofrr`lct`s wmtg MaA9c cktmifem`s

  • 7/22/2019 Novel Vaccines for Defense Against Pneumonic Plague

    39/43

    Sufrun _`ksmka Ofnpfk`kts cs

    Tcoomk`

  • 7/22/2019 Novel Vaccines for Defense Against Pneumonic Plague

    40/43

    M.k. E`lmv`ry fd Sufrun _`ksmka Ofnpfk`kts

    Dcml`e tf Zrft`ot Cacmkst Zk`unfkmo Zlcau`

  • 7/22/2019 Novel Vaccines for Defense Against Pneumonic Plague

    41/43

    Lmnmtctmfks

    Mkcotmvct`e Tcoomk`

    Lmt`rctur`

    Eurctmfk fd Mnnukmty6

    KGZ trmcls kft ofkeuot`e

    D3/T Ca ics`e Tcoomk`s

    Efuit fv`r `ddmocoy mk

    Guncks cs mt emdd`r`ktmclly

    prft`ot Oykfnflausncocqu`s cke Cdrmock

    Ar``k Nfkh`ys

    Ci l`v`ls ef`s kft

    ofrr`lct`s wmtg prft`otmfk mk

    KGZ

  • 7/22/2019 Novel Vaccines for Defense Against Pneumonic Plague

    42/43

    Mnprfv`n`kts cr` Zfssmil`

    Mkcotmvct`e Tcoomk`s

    Fptmnmz` arfwtg ofkemtmfks

    dfr ncxmnun `xpr`ssmfk fd

    prft`otmv` cktma`ks

    I`tt`r mkcotmvctmfk prfo`eur`s

    @kocpsulctmfk2

    _cd`ty,

    _mkal`-efs`,

    Ncy cirfact` tg` r`qumr`n`ktfd cebuvckt iy `kocpsulctmka

    gmag-efs` cke slfw r`l`cs`

    D3/T Ca ics`e Tcoomk`s

    @kocpsulctmfk

    Mkolusmfk fd kfv`l prft`otmv`

    Cas / lfw efs` m]p

  • 7/22/2019 Novel Vaccines for Defense Against Pneumonic Plague

    43/43

    Ugckh yfu