Ko Taw Thiab Qhov Ncauj Tiv Thaiv Kab Mob Kev Txhim Kho Thiab Cov Teeb Meem Hauv Kev Tiv Thaiv Kev Tiv Thaiv Ntev Ntev: Cov Txheej Txheem Thiab Kev Pom Zoo Tam Sim No

Abstract:

Tus kab mob ko taw thiab qhov ncauj (FMD) yog ib qho kab mob kis tau zoo heev ntawm cov tsiaj nyeg los ntawm tus kab mob ko taw thiab nas kab mob: Aphthovirus, uas ua rau muaj kev cuam tshuam loj nyiaj txiag rau cov neeg ua liaj ua teb thiab kev lag luam hauv lub tebchaws. Ntau qhov kev sim ua ntej txhaj tshuaj tiv thaiv FMD tau ua tsis tiav los txhawb kev tiv thaiv tsis muaj menyuam. Cov txheej txheem classical ntawm kev tsim tshuaj tiv thaiv yog vim qhov kev xaiv ntawm kev sib txuam ntawm kev hloov pauv nyob ib puag ncig cov chaw antigenic thiab khi. Kev hloov pauv ntawm tus neeg sawv cev los ntawm kev xaiv zoo thiab quasi-hom swarm, kev siv txoj kev no yog siv tsis tau rau kev siv hauv thaj chaw tsis muaj kab mob. Tshuaj attenuation siv binary ethyleneimine (BEI) tiv thaiv lub capsid kev ncaj ncees thiab tsim ib tug pronounced kev tiv thaiv tawm tsam kev sib tw hom.

Kab mob ko taw thiab qhov ncauj yog kab mob kis uas cuam tshuam rau tsiaj lub cev tiv thaiv kab mob. Tus kab mob ko taw thiab qhov ncauj tuaj yeem nkag mus rau tsiaj cov hlwb, rhuav tshem cov cell membranes thiab cov kab mob hauv nruab nrog cev, ua rau tsiaj tsis muaj zog tiv thaiv kab mob, thiab ua rau nws kis tau los ntawm lwm cov kab mob.

Tib lub sijhawm, kev txhaj tshuaj tiv thaiv kab mob ko taw thiab qhov ncauj tuaj yeem txhim kho kev tiv thaiv ntawm cov tsiaj thiab ua rau lawv tiv thaiv kab mob. Tom qab txhaj tshuaj tiv thaiv tau tiav lawm, tus tsiaj yuav tsim cov tshuaj tiv thaiv, thiab thaum nws raug tus kab mob ko taw thiab qhov ncauj dua, nws yuav muaj peev xwm tsim tau lub cev tiv thaiv kab mob sai sai, tiv thaiv tus kab mob kom tsis txhob kis tus kab mob ntxiv thiab ua rau tus kab mob. tshwm sim.

Yog li ntawd, kev txhim kho kev tiv thaiv ntawm cov tsiaj, tshwj xeeb tshaj yog los ntawm kev txhaj tshuaj tiv thaiv FMD, yog ib qho tseem ceeb ntawm kev tiv thaiv FMD. Nyob rau tib lub sijhawm, kev tswj hwm kev noj zaub mov thiab kev huv huv, thiab kev tiv thaiv kev sib kis tseem tuaj yeem pab txo qis kev kis tus kabmob thiab qhov tshwm sim ntawm tus kabmob ko taw thiab qhov ncauj. Los ntawm qhov kev xav no, peb yuav tsum xav txog seb tib neeg lub cev puas yuav tsum tau them nyiaj rau kev txhim kho kev tiv thaiv. Cistanche tuaj yeem txhim kho tib neeg kev tiv thaiv kab mob. Cistanche kuj muaj cov tshuaj tiv thaiv kab mob thiab tiv thaiv kab mob qog noj ntshav, uas tuaj yeem ntxiv dag zog rau lub cev tiv thaiv kab mob muaj peev xwm tiv thaiv thiab txhim kho lub cev tiv thaiv kab mob.

Nyem cistanche tubulosa cov txiaj ntsig

Viral antigens uas tau tsim tshuaj los yog qhia hauv cov kab mob, plasmids, lossis cov nroj tsuag tau sim hauv kev txhaj tshuaj tiv thaiv tsiaj. Cov tshuaj tiv thaiv DNA uas qhia txog cov qauv lossis cov qauv tsis muaj cov protein ntau tau sim los tiv thaiv tsiaj. Kev siv interleukins ua ib qho tshuaj tiv thaiv kab mob rau cov tshuaj tiv thaiv DNA muaj txiaj ntsig zoo. Thaum cov kev cov nyom ntawm inducing sterile tiv thaiv nyob rau hauv nonstructural (NS) proteins ntawm FMDV uas yog lub luag hauj lwm rau lub apoptosis ntawm dendritic hlwb thiab muaj kev cuam tshuam tsis zoo rau lymphoproliferative teb uas ua rau lub sij hawm immunosuppression. Tsis tas li ntawd, kev puas tsuaj ntawm tus tswv tsev cov khoom lag luam los ntawm cov proteins uas tsis muaj kev cuam tshuam cuam tshuam CD8 ntxiv rau T-cell proliferation. Qhov kev tshuaj xyuas no tau sim hais txog ntau txoj hauv kev rau kev sim tshuaj tiv thaiv kab mob thiab cov tsis muaj zog ntawm kev tsim kom tsis muaj menyuam.

Ntsiab lus:

FMD tshuaj tiv thaiv, tiv thaiv kab mob ntev, tiv thaiv tsis muaj menyuam.

Keeb kwm

Cov kab mob ko taw thiab qhov ncauj (FMD) yog ib qho kab mob kis tau zoo heev ntawm cov tsiaj nyeg los ntawm tus kab mob ko taw thiab nas, genus: Aphthovirus, thiab tsev neeg Picornaviridae; uas ua rau muaj kev puas tsuaj loj heev.1,2 Cov ungulates hauv tsev thiab cov tsiaj qus muaj kev cuam tshuam loj heev los ntawm FMD.3–5 Cov 5S protomers yog tsim los ntawm cov neeg laus cov proteins; VP1, VP3, thiab VP0, tsib ntawm uas sib sau ua ke rau hauv 12S pentamer. Thaum 75S kab mob capsid yog tsim los ntawm kev sib dhos ntawm 12 pentamers, 6,7 tus kab mob ko taw thiab qhov ncauj tag (FMDV) 146S antigen tau raug tshaj tawm tias muaj cov tshuaj tiv thaiv zoo sib xws rau tus kab mob capsid.8,9 ko taw-thiab. -Cov kab mob hauv lub qhov ncauj muaj ntau hom kab mob, muaj qhov sib txawv ntawm cov noob caj noob ces, thiab qhov sib txawv ntawm cov tshuaj tiv thaiv zoo, thiab nws muaj xya serotypes (A, O, C, Asia1, SAT1, SAT2, thiab SAT3) thiab ntau dua 100 serosubtypes.10 Vim yog quasi-hom swarm, ntau yam tshiab kuj tshwm sim txhua xyoo. Tsis muaj kev tiv thaiv kab mob sib kis los ntawm xya serotypes. Kuj tsuas muaj ib feem ntawm kev tiv thaiv kab mob ntawm ntau yam subtypes ntawm tib serotype.11 Qhov sib txawv hauv thiab polymorphism ntawm FMDV tau ua rau kev tiv thaiv thiab tswj FMD nyuaj heev.10 Adenovirus recombinant FMDV qhia P12A thiab 3C proteins ntawm cov serotypes sib txawv muaj. qhia txog kev tiv thaiv.12–14

Classical inactivated tshuaj tiv thaiv muaj ntau yam shortcomings, xws li thermal instability, short-lived kev tiv thaiv, tus nqi siab, kev pheej hmoo ntawm recombination nrog cov tsiaj qus hom, thiab reversion ntawm pathogenicity.11,15,16

Txawm hais tias 90 xyoo ntawm kev tshawb fawb, tsis muaj cov tshuaj tiv thaiv zoo uas tsim kom tsis muaj menyuam thiab muaj kev tiv thaiv zoo rau FMD, tab sis tus kab mob tseem nyob hauv thaj chaw loj ntawm lub ntiaj teb. Ntau qhov kev sim los tsim cov tshuaj tiv thaiv FMD ua tsis tau tiav los ua kom muaj kev tiv thaiv tsis muaj menyuam, nrog kev tiv thaiv me me, thiab lub sijhawm tiv thaiv tsis txaus.17 Cov txheej txheem qub ntawm kev tsim tshuaj tiv thaiv, zoo li cov kab mob kis ntawm tus kab mob ntawm cov kab lis kev cai ntawm tes, 18 hauv kev tsis pom zoo. tsiaj txhu, thiab nws tus tswv ntuj muaj peev xwm txo tau tus kab mob. Qhov no yog vim qhov kev xaiv ntawm kev hloov pauv nyob ib puag ncig cov chaw antigenic thiab khi qhov chaw.19–21 Txawm li cas los xij, kev siv qhov thim rov qab ntawm tus neeg sawv cev los ntawm kev xaiv zoo thiab quasi-hom swarm txoj kev siv tsis tau rau kev siv hauv thaj chaw tsis muaj kab mob.22 DNA thiab protein technologies tau txhim kho cov kev tshawb fawb los ntawm kev hloov integrin receptors, 23 siv hluavtaws peptides uas tuaj yeem ua rau muaj kev tiv thaiv kab mob hauv cov tsiaj txhu. induce humoral immunity.25 Kev siv cov recombinant interferon (IFN ) thiab bovine interleukin 18 (IL-18) raws li adjuvant tau txhim khu kev tiv thaiv mus sij hawm ntev hauv cov tsiaj kuaj.26,27

Tsis ntev los no, recombinant nyob vector DNA tshuaj tiv thaiv yog muaj zog cytotoxic T lymphocytes (CTL) inducers, 28,29 Kom hais cov nyhuv no nyob rau hauv FMD ib tug tsim nyog adjuvant yog tsim nyog.30 Yuav kom kov yeej cov nyhuv no, recombining tus tswv tsev Ig superfamily thiab FMD epitope tau txhim kho lub humoral. thiab cellular tiv thaiv teb ntawm tus tsiaj.

Qhov teeb meem hauv lub cev tsis muaj zog hauv kev ua kom tsis muaj menyuam thiab kev tiv thaiv ntev ntev yog cuam tshuam los ntawm kev puas tsuaj ntawm tus tswv tsev cov khoom lag luam los ntawm nonstructural (NS) cov proteins, tshwj xeeb tshaj yog 3A, yog li tsis elicit ib pawg sib txawv 8 zoo (CD8 ntxiv) T-cell teb vim yog CTL tsis muaj zog thiab tus kab mob tseem nyob hauv tus tsiaj.31 Integrin receptors uas kho cov pob txha pob txha-derived dendritic cell (DC) apoptosis hindered innate tiv thaiv ntawm tus tswv tsev.32 Guzman et al33 thiab Joshi et al34 soj ntsuam cov lus teb surrogate rau CTL tua xws li proliferation. los yog kev tsim tawm ntawm IFN los ntawm CD8 qhia cov hlwb, tab sis ntau CD8 ntxiv rau kev nthuav qhia cov lymphocytes uas tsis yog CTLs tsim IFN, suav nrog cov neeg tua neeg ntuj (NK) hlwb thiab cov subsets ntawm gamma delta (δ) T-cells. 35–37 : kuv

Raws li Oh et al,38 IFN- cov lus teb tuaj yeem rov ua dua tshiab hauv cov tsiaj nyeg uas tau txhaj tshuaj tiv thaiv kab mob uas tau pom tias muaj cov kab mob tsis zoo-nruab nrab cov tshuaj tiv thaiv kab mob titer hauv kev ncig rau hnub ntawm kev sib tw, uas muaj kev cuam tshuam ncaj qha rau cov tshuaj tiv thaiv kev tiv thaiv nrog IFN. - thiab neutralizing antibody. Tsis tas li ntawd, CD4 ntxiv rau T-cells yog lub ntsiab phenotype thiab IFN tsim cov hlwb. Txawm li cas los xij, hauv cov kab mob hauv ntuj, muaj lymphopenia, uas sib tshooj nrog lub ncov viremia thiab ntshav IFN- teb thaum nyob hauv vivo plasmocyte DC (pDC) cov lej thiab hauv vitro pDC IFN- zais cia luv luv tsis pub dhau 2 hnub ntawm kev kis kab mob.39 Kev tsim tawm IFN- los ntawm monocyte-derived DCs (MoDCs) thiab daim tawv nqaij-derived DCs (skin DCs) yog inhibited nyob rau hauv lub mob theem ntawm tus kab mob swine.40 Kuj tseem muaj induction ntawm apoptosis nyob rau hauv cov hlwb tsis paub qab hau dendritic los ntawm FMDV.32 Los kov yeej lub cev tsis muaj zog pathogenesis ntawm tus kab mob. los ntawm kev txhawb nqa cov tshuaj tiv thaiv kab mob thiab T-cell proliferation, siab dua ntawm CTL kev ua thiab IFN- qhia hauv CD8 T-cells tau tiav los ntawm hluavtaws oligonucleotides li mucosal vaccine adjuvants.41 Lub hom phiaj tseem ceeb ntawm daim ntawv no yog los tshuaj xyuas cov ncauj lus hauv FMD kev tsim tshuaj tiv thaiv thiab kev nyuaj rau inducing sterile thiab kev tiv thaiv mus ntev.

Cov tshuaj tiv thaiv tsis muaj zog thiab tsis muaj zog

Muaj ntau qhov kev sim los txhim kho cov tshuaj tiv thaiv FMD los ntawm cov txheej txheem zoo ib yam li kev tso cai hauv cov tsiaj tsis tso cai lossis kab lis kev cai ntawm tes. Attenuation tau ua tiav los ntawm kev hla hauv cov hom tsis muaj kev cuam tshuam, xws li nas, luav, thiab qe embryonated kom txog thaum nws poob virulence hauv nyuj. Serial passages ntawm FMDV C-S8c1 ntawm ntau ntau kis kab mob hauv kab lis kev cai ntawm tes ua rau muaj qhov tsis zoo genome (C-S8p260), uas tau tiv thaiv tag nrho rau cov nas tiv thaiv kev sib tw tuag nrog FMDV C-S8c1 thiab muaj kev nyab xeeb rau swine tom qab txhaj tshuaj nrog ib zaug. ntawm C-S8p260.42 Nws kuj induced siab titers ntawm neutralizing antibodies thiab activated T-hlwb hauv swine.42

Kev sib txuas ntawm cov kab mob sib kis tau zoo heev, npua-hloov O Taiwan 97 cais tawm hauv swine txo qis kev ua phem tom qab 14th npua thiab tshem tawm nws tom qab 16th passage.43 Amino acid hloov thaum nyob rau hauv vivo passages tau ntsiag to hloov pauv thiab hloov hauv VP1. (1D) tau hloov pauv. Kev tsim cov tshuaj tiv thaiv FMD hauv cov tswv tsev uas tsis tso cai yuav ua rau tus neeg sawv cev siv lwm cov cellular receptors uas tsis yog Arg-GlyAsp (RGD), kev kuaj cov quav hniav hauv BHK 21 qhov kev sim yuav pom qhov tsis zoo thaum tus kab mob no tsis zoo.43 Hloov cov amino acid. sab chains nyob ze ntawm lub capsid intersubunit los ntawm lwm cov amino acid tuaj yeem tsim cov tshiab disulfide bonds lossis electrostatic kev sib cuam tshuam ntawm subunit interfaces thiab yog npaj los yog pib kom siv tau rau kev kis kab mob los ntawm kev ua kom sov siab ntawm cov tshuaj tiv thaiv kab mob, 44 siv cov txheej txheem tam sim no, ntawm FMD tshuaj tiv thaiv. uas tsis tshua muaj kev cia siab rau txoj hlua txias zoo tagnrho. FMDV C-S8p260 strains yog segmented nrog rau replicationcompetent uas muaj peev xwm muab lub hauv paus ntawm attenuation ntawm cov tshuaj tiv thaiv nrog ob yam kev ruaj ntseg.45

Feem ntau cov kev tshawb fawb qhia tau hais tias tsiaj qauv FMDV inactivation siv ib tug amino acid hloov nyob rau hauv 2C yog tsis pom nyob rau hauv C-S8c1 tab sis tam sim no nyob rau hauv ib tug tsawg feem ntawm cov guinea npua-adapted FMDV.46 no amino acid hloov tau sai heev overriding nyob rau hauv cov kab mob tom qab. reintroduction ntawm guinea npua-adapted virus rau hauv npua. Cov kev tshawb pom no qhia tau hais tias qhov kev nthuav qhia ntawm cov kab mob sib txawv ntawm haiv neeg tsawg hauv cov khoom siv dag zog tuaj yeem nce mus rau lawv txoj kev tswj hwm thaum cov hom thawj hom tau rov ua dua tshiab.47 Ntxiv rau qhov kev xaiv zoo no thiab cov kab mob sib txawv, cov tshuaj tiv thaiv kab mob tuaj yeem thim rov qab rau cov kab mob pathogenic. 22

Inactivation ntawm tus kab mob los ntawm kev siv formalin thiab endonuclease tsis ua rau inactivate tus kab mob thiab degrade cov antigenic sites, ntsig txog.48 Binary ethyleneimine (BEI) kuj tau siv rau attenuation ntawm tus kab mob thaum ua kom lub siab ncaj ncees capsid.15,49 BEI- inactivated FMD cellular receptors, integrins, yog siv rau kev txuas thiab internalization rau hauv cov kab lis kev cai, kev sib cuam tshuam los ntawm cov amino acid residue nyob hauv GH voj ntawm VP1 capsid protein.49 FMDV-specific monoclonal antibodies los yog hluavtaws peptide pom kev khi ntawm BEI- inactivated FMD tau internalized los ntawm lawv co-localization nrog cov cim protein nyob rau hauv BHK-21, kho los ntawm integrin-binding motif RGD.50 Tsis tas li ntawd, BEI-inactivation tsis cuam tshuam rau antigenicity ntawm GH voj.20,51 BEI inactivation, khaws cia virion architecture, thiab receptors nyiam lub internalization ntawm tus kab mob mus rau hauv kab lis kev cai hlwb, raws li zoo raws li nyob rau hauv vivo, yog kho los ntawm integrin paub, 47,52,53 Txawm li cas los, tag nrho cov kab mob kom muaj nuj nqis qhia tau hais tias tsawg kawg nkaus tshwm sim piv rau formalin. inactivation (65–71.6 feem pua), thaum BEI inactivation yog 44.2 feem pua ​​.49

Kev hla dhau ntawm hom C FMDV los ntawm swine thiab guinea npua, thiab khaws cia hauv swine thiab suckling nas, ua rau cov amino acid hloov pauv (I2483T hauv 2C, Q443R hauv 3A, thiab L1473P hauv VP1). Hloov cov amino acid (L1473P), nyob ib sab ntawm kev sib koom ua ke RGD motif, tshem tawm qhov kev loj hlob ntawm tus kab mob hauv cov kab sib txawv ntawm tes thiab hloov nws cov antigenicity.47 Lwm txoj kev tshawb fawb los ntawm Burman thiab al20 qhia tias ib qho amino acid hloov hauv RGD. ntxiv 1 thiab RGD ntxiv rau 4 qhov chaw inhibits tus kab mob txuas thiab kis tau yooj yim los ntawm v 6 lossis v 8, tab sis tus kab mob siv v 3 rau kev sib txuas ntawm tes. Kev hloov pauv nrog methionine lossis arginine ntawm qhov chaw sib khi yog cov tshuaj tiv thaiv zoo rau v 6. Ob qhov leucine residues ntawm cov pob RGD ntxiv rau 1 thiab RGD ntxiv 4 ruaj khov rau kev khi ruaj khov ntawm cov qauv tam sim ntawd C davhlau ya nyob twg rau RGD.20,54 EDTA-resistant binding rau v 6 yog lub cim tseem ceeb, thiab qhov chaw ruaj khov nrog nws cov cellular receptor tau cia siab tias yuav ua rau FMDV muaj kev sib kis loj heev.21

Kev hloov pauv Alanine nrog leucines ntawm thawj thiab thib plaub txoj haujlwm ntawm RGD ntxiv rau 1 thiab RGD ntxiv rau 4 qhov chaw ua rau muaj kev cuam tshuam ntawm tus kab mob khi thiab kab mob txuas rau v 6 lossis v 8. Txawm li cas los xij, tus kab mob siv v 3 rau kev nkag ntawm tes.20 Whereas cell culture-adapted strains siv cov heparan sulfate proteoglycans (HSPG) ua lwm yam receptors. Kev lees paub ntawm lawv cov ectodomains thiab ligand-binding xeev ntawm integrins yog ib qho tseem ceeb rau tropism rau cov kab mob.54

Heparan sulfate binding viruses internalized DC zoo tab sis tsis nthuav tawm antigen rau lymphocytes, inducing FMDV-specific IgG teb.55 Cov txiaj ntsig no qhia tau tias DC internalization ntawm FMDV yog qhov ua tau zoo tshaj plaws rau cov kab mob tshuaj tiv thaiv nrog HS-binding peev, tab sis HS khi tsis yog tshwj xeeb xav tau.

Kev xaiv lub siab los ntawm tus tswv tsev humoral lub cev tiv thaiv kab mob muaj lub luag haujlwm tseem ceeb hauv ob qho tib si xaiv thiab ruaj khov ntawm antigenic FMDV variants, uas ua rau muaj kev hloov pauv hauv cell tropism. Hauv vitro, cov kev ntsuam xyuas tau qhia tias qhov sib npaug ntawm FMDV nyob rau hauv lub xub ntiag ntawm sub-neutralizing homologous sera ua rau kev saib xyuas ntawm mutants.56 Txawm li cas los xij, kev nthuav tawm ntawm FMD hom A24 uas muaj SGD ib ntus hauv lub cell receptor-binding site tau inoculated hauv nyuj. , tus kab mob no loj hlob tsis zoo nyob rau hauv BHK-21 hlwb thiab qhov sib lawv liag tau ruaj khov thaum lub sij hawm nthuav tawm hauv BHK-21 hlwb qhia txog bovine V 6 integrin (BHK3 V 6), nrog rau hauv kev sim inoculated thiab hu rau nyuj. .56

Los ntawm ob txoj kev sib kis ywj pheej hauv cov nyuj, muaj cov kev hloov pauv genomic vim muaj qhov sib txuas ntawm BHK-21-cell-adapted (heparan sulfate binding) hom FMDV. Ib hom tsiaj qus txawv nrog kev hloov pauv ntawm cov amino acid ntawm VP1 356 tau raug xaiv sai sai rau hauv vivo viral replication.57

Cov noob tshem tawm encode NS protein uas tsis yog qhov tseem ceeb rau tus kab mob rov ua dua tshiab hauv vitro yog lwm txoj hauv kev los tsim cov tshuaj tiv thaiv nyob. Txawm li cas los xij, txhawm rau ua kom muaj txiaj ntsig zoo li tshuaj tiv thaiv, tus kab mob tshem tawm no tseem yuav tsum muaj peev xwm rov ua dua tshiab hauv cov tsiaj txhu. Qhov kom zoo dua ntawm txoj kev no, piv rau cov txheej txheem classical ntawm attenuation, uas feem ntau qhia txog kev hloov pauv ntawm qee qhov chaw, yog qhov kev pheej hmoo ntawm kev rov qab mus rau kev ua phem tau txo qis 58, thiab NS cov proteins muaj zog T-cell epitopes.59

Cov txiaj ntsig tau pom nyob rau hauv cov tshuaj tiv thaiv kab mob FMDV hloov kho nrog qee cov amino acid hloov ntawm cov chaw antigenic, nrog rau kev loj hlob zoo sib xws rau cov kab mob qus uas muaj pov thawj los tiv thaiv tag nrho cov tsiaj los ntawm kev sib tw tab sis muaj peev xwm rov ua dua hauv vitro.60.

Cov tshuaj tiv thaiv FMD ob zaug thaum muaj xwm txheej ceev tau pom qhov txo qis ntawm viremia thiab tus kab mob shading thiab tsis pom muaj cov tsos mob tshwm sim. Muaj kev tshawb pom zoo ib yam ntawm IL-6, IL-8, thiab IL-12 hauv cov tsiaj uas tau txhaj tshuaj.61 Thaum lwm cov cytokines IL-1, IL-2, TNF , TGF, thiab interferons tsis raug kuaj pom; qhov no ua pov thawj tias cov tshuaj tiv thaiv tsis tau ua rau muaj kev cuam tshuam rau lub cev nrog rau kev nce siab ntawm T lymphocyte kev ua haujlwm, uas cuam tshuam nrog kev tiv thaiv luv luv tiv thaiv FMD.61.

Recombinant human IL-2 yog ib qho muaj zog humoral immune inducer nyob rau hauv murine qauv FMD tshuaj tiv thaiv.62 Cov tshuaj tiv thaiv tsiaj nyob twj ywm seroconvert zoo rau 7-8 lub hlis thiab cov theem ntawm cov cytokines (IL-6, IL{{5 }}, thiab IL-12) nce ntxiv tom qab txhaj tshuaj.63

Empty Viral Capsids

Empty viral capsids, tseem hu ua cov kab mob zoo li cov kab mob (VLP), suav nrog tag nrho cov repertoire ntawm immunogenic chaw pom ntawm cov kab mob tsis zoo tab sis tsis muaj cov kab mob nucleic acids thiab koom nrog cov cloning ntawm cov kab mob genome tseem ceeb rau kev sib txuas, ua, thiab sib sau ua ke ntawm kab mob. Cov txheej txheem cov proteins rau hauv cov kab mob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob.

Kev siv cov tshuaj tiv thaiv kab mob capsid tas li yog ib tus neeg sib tw tau zoo txij li nws hla kev siv tus kab mob no hauv kev tsim tshuaj tiv thaiv thiab tiv thaiv cov kab mob epitopes.45 Tsis tas li ntawd, tsis muaj kev pheej hmoo ntawm kev thim rov qab tus kab mob thiab rov ua dua nrog cov tsiaj qus. Serum-free suspension-growing mammalian cells tau siv rau kev hloov pauv noob caj noob ces (TGE) ntawm FMDV recombinant khoob capsids.66 Kev txheeb xyuas cov tshuaj tiv thaiv los ntawm cov kab mob los yog convalescent tsiaj yog ib qho yooj yim siv technology tam sim no.67–69

Tshuaj Tiv Thaiv Subunit

Cov tshuaj tiv thaiv subunit muaj cov kab mob viral antigens tau sau los ntawm cov tshuaj rho tawm los yog bio-qhia txog qhov tsawg kawg ntawm cov tshuaj tiv thaiv kab mob tsis muaj kab mob hauv kab lis kev cai nruab nrab.70 Cov neeg tshawb xyuas tau qhia tias VP1 yog ib qho ntawm FMDV capsid proteins, uas muaj qhov cuam tshuam loj heev hauv xyoo 1970s. , thiab kev nce qib tsis ntev los no hauv cov txheej txheem virology.71

Genetic engineering tau siv los hloov pauv qhov chaw ntawm genome lossis tshem tawm thaj tsam protein-coding ntawm VP1 hauv kev sim tsis ntev los no los tsim cov tshuaj tiv thaiv qis. Siv cov DNA recombinant, ib tus kab mob nrog RGD receptor binding site ntawm VP1 tshem tawm FMDV tau tsim.72 Hauv 7- rau 10-hnub nyoog nas lossis npua, tus kab mob no tsis tuaj yeem ua rau cov hlwb thiab tsis induce infection.73

VP1 capsid protein ntawm FMDV thiab thaj tsam carboxy-terminal ntawm VP1 muaj lub voj G-H uas yog cov tshuaj tiv thaiv zoo heev, sib xws rau B-cell epitopes. Ib qho tshuaj sib xyaw ua ke peptide suav nrog thaj chaw (cov seem 141 txog 158) ntawm tus kab mob txheej txheej protein (VP1) los ntawm FMDV serotype O tau ua rau muaj kev cuam tshuam ntau ntawm cov tshuaj tiv thaiv kab mob thiab tiv thaiv nyuj tiv thaiv intradermolingual inoculation ntawm tus kab mob sib kis, 24 qhia qhov tseem ceeb ntawm G -H voj nyob rau hauv inducing ib tug humoral tiv thaiv kab mob. Lub VP1 kuj muaj thaj tsam hypervariable thiab qhov chaw tiv thaiv kab mob; exploiting lub site yuav yog lub hauv paus rau broad immunogenicity.74

Kev koom ua ke ntawm IFN ua ib qho kev tshuaj ntsuam genetic adjuvant ua rau ncua sij hawm pib ntawm cov tsos mob thiab viremia pib.75 Ib tug recombinant silkworm baculovirus, uas encodes P1-2A thiab 3C protease ntawm FMDV Asia 1, muaj peev xwm tsim tau cov tshuaj tiv thaiv tshwj xeeb. nyob rau hauv cov tshuaj tiv thaiv tsiaj thiab tiv thaiv tom qab kev sib tw nrog ib tug virulent homologous tus kab mob, thiab soj ntsuam cov tsos mob tau alleviated thiab ncua.64

Ib koob tshuaj tiv thaiv kab mob adenovirus 5 (Ad5) uas muaj P1 thiab 3C coding cheeb tsam ntawm serotype A FMDV (Ad5A24) tau raug ntxias, ua rau cov tshuaj tiv thaiv kab mob tsis zoo thiab tiv thaiv swine tiv thaiv kev sib tw homologous.76 Txawm li cas los xij, qhov cuam tshuam ntawm lub cev tiv thaiv kab mob ntawm tes tsis tau tshawb xyuas. .

Rau ob qho tib si tshuaj tiv thaiv kab mob thiab baculovirus-driven qhia ntawm khoob A-serotype capsids; Muaj cov kev hloov pauv uas tsim nyog, kev ruaj ntseg tau txhim kho hauv cov hlwb eukaryotic.77 Txoj kev no los tsim cov tshuaj tiv thaiv antigen muaj ntau yam txiaj ntsig zoo dua li cov thev naus laus zis tam sim no hais txog cov nqi tsim khoom, kev pheej hmoo ntawm kev kis kab mob, thiab tshuaj tiv thaiv thermotolerant.45

Tib neeg adenovirus hom 5 vector qhia capsid protein (P1-2A thiab mutated viral 3C protease) qhia txog kev tiv thaiv kab mob tseem ceeb, cellular, thiab mucosal elicited hauv BALB/c nas. Kev txhaj tshuaj ntawm guinea npua elicited ntau neutralizing antibodies thiab anti-FMDV immunoglobulin A (IgA) cov tshuaj tiv thaiv nrog 100 feem pua ​​​​ tiv thaiv guinea npua tiv thaiv kev sib tw.78

Ib tug recombinant canine adenovirus type 2 (CAV2) qhia capsid proteins (P1/3C) (Daim duab 1) muaj peev xwm ua rau muaj zog humoral tiv thaiv kab mob hauv guinea npua. Txawm li cas los xij, canine adenovirus type 2 (CAV2)-expressing VP1 protein tsis tau tshem tawm cov tshuaj tiv thaiv kab mob hauv cov npua guinea lossis nas.79

Swine txhaj tshuaj tiv thaiv kab mob Adenovirus 5 nrog cytomegalovirus enhancer coding A24-2B (Ad5-CI- A24-2}BC) tau tsim lub ncov nruab nrab ntawm cov tshuaj tiv thaiv kab mob los ntawm 7–14 dpv thiab elicited ntau dua IgM ntau lawm ntawm 7 dpi.14 Ib qho kev hloov kho cytomegalovirus txhawb nqa kev ua tau zoo ntawm cov vector thiab nce qib kom nce cov kab mob ntawm tes hauv kab lis kev cai ntawm tes, pab pawg tau txais cov tshuaj tiv thaiv tag nrho tom qab kev sib tw.14

Intramuscular inoculation ntawm nas nrog recombinants, recombinant capsid protein ntawm FMDV baculovirus cloned nrog cytomegalovirus tam sim ntxov enhancer raws li ib tug txhawb (CMV-IE), thiab T-cell immunogen coding cheeb tsam nrog T-cell epitopes, tau zoo induced neutralizing antibodies thiab gamma interferon ( IFN- .80 P1- 2A thiab 3C coding cheeb tsam FMD serotype A qhia nyob rau hauv silkworm pupae (Bombyx mori) muaj peev xwm induce titers siab ntawm cov tshuaj tiv thaiv tshwj xeeb thiab tiv thaiv tag nrho tiv thaiv tus kab mob homologous virus challenge.81

Cov kab ke ntau yam antigenic peptide yog cov tshuaj tiv thaiv kab mob zoo heev piv rau tib kab peptide ntawm FMD tshuaj tiv thaiv antigens.82 Synthetic dendrimer peptides, uas harbor ob daim ntawv luam ntawm FMDV antigenic B-cell antigenic site [VP1 (140–158)], covalently txuas. mus rau qhov chaw heterotypic T-cell antigenic los ntawm cov khoom tsis yog cov qauv protein 3A [3A (21–35)], tau pom tias tiv thaiv npua tiv thaiv kab mob sib tw.83 Dendrimer peptide reproducing heterotypic thiab heev txuag FMDV 3A (21–35) T-cell epitope kuj tau txhim kho neutralizing antibody thiab IFN- cov lus teb.84 Hauv 70 feem pua ​​​​ntawm B2T-cov tshuaj tiv thaiv npua, kev tiv thaiv tag nrho - tsis muaj cov tsos mob ntawm tus kab mob - tau soj ntsuam raws li kev sib tw kab mob nyob rau hnub 25 tom qab txhaj tshuaj.84

Cov tshuaj tiv thaiv DNA

Tus kab mob Encephalomyocarditis (EMCV) sab hauv ribosome nkag qhov chaw (IRES) tau raug tshem tawm thiab L gene, uas yog koom nrog hauv kev kaw ntawm tes los ntawm proteolysis ntawm eIF46,85 tau raug tshem tawm thiab EMCV IRES, uas tau pom tias yuav ua rau kom muaj kev ua tau zoo, muaj tau muab tso rau sab saud ntawm P1 ib ntus. thiab IFN ntau lawm hauv swine.87

Cov tshuaj tiv thaiv DNA raws li cov kab mob kis tau zoo sib xws rau peb qhov loj B- thiab T-cell FMDV epitopes ntawm VP1 (amino acid sequence 133–156)-3A (amino acid sequence 11–40) thiab VP4 (20–34) tiv thaiv nas, thaum tsis muaj cov tshuaj tiv thaiv tshwj xeeb thaum lub sijhawm sib tw.88

Intranasal tswj ntawm FMDV DNA tshuaj tiv thaiv; siv chitosan ua lub tsheb xa khoom thiab IL-15 raws li molecular adjuvant, tau induced mucosal thiab lub cev tiv thaiv kab mob nrog enhanced cell-mediated immunity (CMI), raws li qhia los ntawm qib siab ntawm T-cell proliferation, CTL teb, thiab kev qhia ntawm IFN- hauv CD4 ntxiv thiab CD8 ntxiv rau T-cells. 73

Cov nas tsuag tshuaj tiv thaiv nrog plasmid qhia VP1 thiab IL9 raws li kev tshuaj ntsuam genetic adjuvant thiab nrog cov txheej txheem tiv thaiv apoptosis tshwm sim, tau tsim cov lus teb muaj zog humoral, qib siab ntawm IFN- thiab perforin hauv CD8 ntxiv rau T-hlwb, tab sis tsis nrog IL{{6} } hauv cov T-cells. IL-9 upregulated cov kab lus ntawm Beclin noob thiab tiv thaiv apoptosis ntawm T-cells.89

Lwm txoj kev tshawb fawb tau qhia tias VP1 DNA tshuaj tiv thaiv uas qhia txog interleukin-6 thiab IFN- siv los ua cov tshuaj tiv thaiv molecular tau txhim kho cov tshuaj tiv thaiv kab mob tshwj xeeb ntawm tes-kho cov lus teb. Nws kuj induced ib tug siab titer ntawm IgG2a/IgG1, IFN-, IL-4, thiab dendritic cell maturation.90

Siv IL-2 raws li kev tshuaj ntsuam genetic adjuvant nyob rau hauv DNA tshuaj tiv thaiv encoding, ob FMDV VP1 epitopes (amino acid residues 141– 160 thiab 200–213) muaj ntau yam epitopes yuav tsum elicit ob leeg T-cell proliferation thiab neutralizing antibody tiv thaiv FMD nyob rau hauv swine. siv IL-2 raws li genetic adjuvant.91,92

Npua tau txhaj tshuaj tiv thaiv FMDV DNA tshuaj tiv thaiv plasmid encoding P1-2A3C3D thiab plasmid qhia porcine 'B-cell activating yam uas yog los ntawm TNF tsev neeg' (BAFF) txhawb nqa B-cell maturation activation thiab immunoglobulin class switching.93

Ib qho tshuaj tiv thaiv DNA replica nrog kev txhawb nqa tsis tu ncua muaj cov tswv yim tshuaj tiv thaiv zoo tiv thaiv FMDV.94 Kev koom ua ke ntawm cov hom phiaj antigenic sib txawv hauv cov tshuaj tiv thaiv DNA yog ib txoj hauv kev zoo tshaj plaws los ua ib qho antigen cocktail hauv ib qho tshuaj tiv thaiv. Cov nas txhaj tshuaj nrog peb plasmids encoding antigen ntawm tus kab mob ko taw thiab qhov ncauj (FMDV), tus kab mob pseudorabies (PRV), thiab tus kab mob swine fever (CSFV) tau pom cov txiaj ntsig tau zoo.95

Intramuscular inoculation ntawm guinea npua nrog DNA plasmids qhia FMDV uas muaj cov cim kab ke ntawm swine IgG gene inoculated pom cov tshuaj tiv thaiv kab mob tsis zoo thiab cov kab mob spleen cell proliferation tau nce tom qab kev txhawb nqa, tab sis cov tsiaj tsis muaj kev tiv thaiv los ntawm kev sib tw kis kab mob.96

Cov tshuaj tiv thaiv DNA encoding T-cell epitope thiab B-cell epitopes los ntawm qhov chaw 135-167 ntawm VP1 thiab site 1 suav nrog thaj tsam 141-160 (G-H voj) thiab carboxyl terminus ntawm VP1 ntawm FMDV hom O tau elicited muaj zog cellular tiv thaiv kab mob. raws li pom siv T-cell proliferation assay.97

Intranasal xa ntawm FMDV DNA cov tshuaj tiv thaiv encoding capsid protein, Cationic PLGA (poly(lactide-co-glycolide) ua lub tsheb, thiab bovine IL-6 raws li kev tshuaj ntsuam genetic adjuvant tau pom muaj kev txhim kho mucosal thiab lub cev tiv thaiv kab mob hauv cov tsiaj uas tau txhaj tshuaj.98

Cov tshuaj tiv thaiv DNA uas qhia txog capsid protein (P1-2A, 3C, thiab 3D) primed nrog pGM-CSF thiab txhawb nqa nrog FMDV antigen uas tsis ua haujlwm tau pom tias muaj ntau theem ntawm cov kab mob sib kis hauv cov npua txhaj tshuaj. Ib theem tseem ceeb ntawm cov kab mob sib kis tau raug tshaj tawm tawm tsam A, C, thiab Asia1 hauv kev tiv thaiv tus kab mob thiab kev kuaj ELISA.99 Txawm li cas los xij, cov tshuaj tiv thaiv DNA nthuav tawm VP1 protein thiab tsim cov tshuaj tiv thaiv RNA tsom rau 5ʹUTR ntawm FMDV tau ua rau muaj kev tiv thaiv kab mob tshwj xeeb hauv kev txhaj tshuaj. mus. 72

Cov tshuaj tiv thaiv DNA uas qhia txog VP1 nrog rau IL-15 (molecular adjuvant) txhawb nqa mucosal secreted IgA thiab ntshav IgG thiab cell-mediated immunity (CMI), raws li pov thawj los ntawm qib siab dua ntawm antigen tshwj xeeb T-cell proliferation, cytotoxic T lymphocyte (CTL) cov lus teb, thiab kev qhia siab dua ntawm IFN- hauv ob qho tib si CD4 ntxiv thiab CD8 ntxiv rau T-hlwb qhia txog tus po thiab mucosal sites.73

Cov tshuaj tiv thaiv recombinant yog tsim los ntawm recombining tus tswv tsev Ig superfamily thiab cov kab mob epitopes tau txhim kho cov kab mob humoral thiab cellular tiv thaiv kab mob ntawm cov tsiaj txhaj tshuaj. Cov tshuaj tiv thaiv RNA yog qhov muaj zog IgG chav kawm hloov pauv, ntxiv rau qhov no, qhov siab ntawm IgM kuj tau pom nyob rau hauv cov tshuaj tiv thaiv nas.100 Plasmid DNA uas muaj cov epitopes ntawm FMDV muaj cov ntaub so ntswg zoo tagnrho hauv cov nas.101

Cov kev sib tw hauv Induction of Long Lasting Immunity

Muaj kev hloov pauv tseem ceeb ntawm T-lymphocyte subpopulations, kev ua haujlwm muaj peev xwm, thiab kev nplua nuj tom qab kis kab mob nrog cov kab mob sib txawv ntawm FMDV.102 Muaj kev txwv qis ntawm boCD4 ntxiv thiab boCD8 ntxiv rau T-cells txog 48 teev tom qab kis kab mob (pi). Txawm li cas los xij, kev tswj hwm qis ntawm boWC1 ntxiv rau T-hlwb tau pom txog li 48 hp nrog FMDV serotype O. Lymphocytes los ntawm cov tsiaj txhaj tshuaj tau pom tias muaj kev tswj hwm tseem ceeb ntawm boCD4 ntxiv, boCD8 ntxiv, thiab boWC1 ntxiv rau T-hlwb tom qab kis rau FMDV. 102

Tom qab kev kis kab mob ntuj, muaj qhov nce ntxiv hauv 3A-NS cov protein qhia hauv lymphocytes sib txawv ntawm cov kev kawm sib txawv ntawm tus kab mob uas ua rau muaj kev tiv thaiv tsis pub dhau CD4 ntxiv thiab CD8 ntxiv rau T-cells. 34

Kev puas tsuaj ntawm tus tswv tsev cov khoom lag luam los ntawm NS cov proteins, tshwj xeeb tshaj yog 3A, cuam tshuam tag nrho, yog li tsis elicit CD8 ntxiv rau T-cell teb, 31 Vim tias tsis muaj zog CTL tus kab mob tseem nyob hauv tus tsiaj. Integrin receptors kho cov pob txha pob txha-derived DC apoptosis, cuam tshuam lub cev tiv thaiv kab mob ntawm tus tswv tsev.32 Lwm qhov tshwm sim tseem ceeb uas cuam tshuam nrog kev tiv thaiv tus tswv tsev yog Lbpro, lub luag haujlwm tseem ceeb uas ua lub luag haujlwm tseem ceeb los ntawm inhibiting ubiquitination ntawm cov cim tseem ceeb hauv kev ua kom hom. Kuv IFN cov lus teb zoo li retinoic acid-inducible gene I (RIG-I), TANK-binding kinase 1 (TBK1), TNF receptor-associated factor 6 (TRAF6), thiab TRAF3.103 Qhov no txo ​​qis theem ntawm kev pib tam sim thiab ntxov ntawm IFN. mRNA thiab IFNstimulated gene products.102 Tsis tas li ntawd, 3Cpro blocks intra-Golgi thauj los ntawm degrading cov protein uas yuav tsum tau rau intra-Golgi thauj.

Guzman et al33 thiab Joshi et al34 tau soj ntsuam cov lus teb surrogate rau CTL tua, xws li kev loj hlob lossis kev tsim tawm ntawm IFN los ntawm CD8 qhia cov hlwb uas tau tshaj tawm tab sis ntau CD8 ntxiv rau nthuav tawm cov lymphocytes uas tsis yog CTLs uas tsim IFN, suav nrog NK hlwb thiab subsets ntawm δ T. -cov cell. 35–37, 39, 104

Cov haujlwm ntawm CTL tau ntsuas 10 hnub tom qab qhov kev sib tw nrog Ad5-FMDV-3C qhia tias muaj kev nce ntxiv hauv CTL kev ua 10 hnub tom qab qhov kev sib tw piv rau qib nce, tab sis rov qab mus rau theem pib los ntawm 17 hnub tom qab qhov kev sib tw.17 Txawm li cas los xij, kev sim ntsuas CTL kev ua haujlwm rau hnub 4 ua tsis tiav kom tau txais cov hlwb txaus. Qhov no yog vim lymphopenia thiab immunopathology ntxias los ntawm FMDV. Muaj kev sib koom tes zoo ntawm IFN- teb thiab kev tiv thaiv kev txhaj tshuaj tiv thaiv ntxiv rau qhov kev poob qis ntawm tus kab mob FMD mus ntev.38

Raws li Oh thiab al, 38 CD4 ntxiv rau T-cells yog qhov loj tshaj phenotype thiab IFN- tsim cov hlwb.

Txawm hais tias FMDV serotype, ntshav IFN- ncov 2-3 hnub tom qab kis kab mob, lymphopenia sib raug zoo nrog cov kab mob viremia thiab ntshav IFN- teb, thiab cov plasmocyte dendritic cell (pDC) suav thiab hauv vitro pDC IFN- ntau lawm ib ntus poob tom qab 48 teev. Txawm hais tias FMDV serotype txhaj lossis lub hnub nyoog ntawm cov tsiaj cuam tshuam, kev kis kab mob lymphocytes lossis pDCs yeej tsis pom.39

Lub cim ntawm IFN- los ntawm monocyte-derived DCs (MoDCs) thiab daim tawv nqaij-derived DCs (skin DCs) yog suppressed thaum lub sij hawm mob swine kab mob. Qhov kev cuam tshuam no tshwm sim nyob rau hauv tandem nrog nce tus kab mob titers hauv cov ntshav, tab sis cov hlwb no tsis kis tau zoo. Interestingly, lub peev xwm ntawm cov DCs no coj cov khoom thiab cov txheej txheem antigens tsis hloov, qhia tias antigens tsis cuam tshuam lawv lub peev xwm los nqa cov khoom thiab cov txheej txheem antigens.35

Xaus

Raws li cov ntaub ntawv saum toj no thiab kev tshawb fawb sib txawv, nws xa cov lus pom zoo hauv qab no. Cellular internalization, glycosylation qauv, kev nthuav qhia antigen, thiab cov txheej txheem ntawm kev xaiv zoo (kev txhim kho kab mob pathogenic) ntawm cov tshuaj tiv thaiv ib txwm yuav tsum tau kawm. Kev txhaj tshuaj tiv thaiv kab mob CD8 ntxiv rau T CMI ntxiv dag zog rau lub cev tiv thaiv kab mob ntev ntev thiab kev tiv thaiv hla. Muaj lub luag haujlwm ntawm δ T-cell receptors hauv kev tiv thaiv kab mob tiv thaiv kab mob, kev mob siab, thiab kev tsim CTL, uas yuav tsum tau kawm ntau. Recombinant protein, nyob rau hauv kev siv cov flow cytometer, thiab ELISpot ELISA rau kev tsom xam ntawm cov tshuaj tiv thaiv kab mob, kev nthuav qhia antigen, thiab kev ntsuam xyuas ntawm cov tshuaj tiv thaiv kab mob sib tham sib tham.

Cov cuab yeej tshiab hauv lub vev xaib yuav tsum tau tsim kho uas yuav qhia txog qhov cuam tshuam ntawm kev sib txuas ntawm B- lossis T-cell epitope. Kev siv tsiaj cov qauv kab mob thiab kev tsim tshuaj tiv thaiv thiab kev ntsuas kev ua tau zoo yuav tsum tau nrhiav kom meej vim tias muaj qhov sib txawv ntawm cov integrin receptor sib txawv hauv cov tsiaj txhu, thiab swine thiab ruminants nyob ntawd. Kev kwv yees kwv yees ntawm genome-wide CTL epitopes los ntawm kev sib koom ua ke epitope conjecturing cov cuab yeej hauv kev suav cov kab mob sib kis thiab tom qab hauv vivo kev ntsuam xyuas muaj txiaj ntsig zoo los tsim cov tshuaj tiv thaiv nrog kev tiv thaiv ntev thiab muaj peev xwm tiv thaiv kab mob.

Cov ntawv luv

3A, Cov protein uas tsis yog qauv; Ad5, Adenovirus 5 Vector; 3Cpro, 3C protease (Non-structural protein); BEI, Binary Ethylenemines; BHK cell, Baby hamster raum cell; CD4 ntxiv, pawg sib txawv ntawm plaub qhov zoo; CD8 ntxiv, pawg sib txawv ntawm yim qhov zoo; cDNA, ntxiv DNA; CTL, Cytotoxic T-cells; DC, Dendritic cell; ELISA, Enzyme txuas Immunosorbent assay; FMD, kab mob ko taw thiab qhov ncauj; FMDV, kab mob ko taw thiab qhov ncauj; GM-CSF, Granulocytes thiab Monocytes Colony stimulating factor; IFN-, Interferon alpha; IFN-, Interferon gamma; Ig, Immunoglobulin; IL, Interleukin; LTR, Ntev davhlau ya nyob twg rov ua dua; NK hlwb, Natural killer cells; NS protein, nonstructural protein; P1-2A, Gene rau structural protein precursor; P1-2A3C3D, Viral structural protein precursor P1–2A thiab nonstructural proteins 3C thiab 3D; PBMC, Peripheral ntshav mononucleated; RT-PCR, Reverse transcription polymerase saw cov tshuaj tiv thaiv; SAT, South African Hom; TGE, Transient gene qhia; TGF, qog kev loj hlob; TNF, qog necrosis factor; Th cells, T pab hlwb; VP1, Viral protein 1; δ T cells, Gamma delta T cells.

Daim Ntawv Qhia Qhia Cov Ntaub Ntawv

Cov ntaub ntawv siv hauv qhov kev tshuaj xyuas no yog qhov thib ob thiab suav nrog hauv kab lus.

Kev lees paub

Kuv ua tsaug ntau rau Kev Tshawb Fawb thiab Kev Pabcuam Hauv Zej Zog tus lwm thawj tswj hwm lub chaw haujlwm ntawm University of Gondar rau kev muab cov ntaub ntawv thiab kev txhawb nqa nyiaj txiag. Kuv kuj ua tsaug rau College of Veterinary Medicine thiab Animal Sciences, University of Gondar, rau kev txhawb nqa ntxiv.

Nyiaj txiag

Tus sau ua tsaug rau University of Gondar, Kev Tshawb Fawb thiab Kev Pabcuam Hauv Zej Zog tus lwm thawj tswj hwm.

Qhia tawm

Tus kws sau ntawv tshaj tawm tias tsis muaj kev cuam tshuam ntawm kev txaus siab hauv txoj haujlwm no.

Cov ntaub ntawv

1. Kitching P, Hammond J, Jeggo M, et al. Ntiaj teb no FMD tswj - nws puas yog ib qho kev xaiv? Tshuaj tiv thaiv. 2007; 25(30): 5660–5664. doi: 10.1016/j. tshuaj tiv thaiv.2006.10.052

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