Tsis ntev los no ua ntej hauv Tick Antigen Discovery Thiab Anti-Tick Vaccine Development Part 2

2.4. Malpighian-Associated Antigen Cov neeg sib tw

Hauv cov kab mob uas muaj sia nyob, 50 -nucleotidases yog ib pawg enzymes dav dav hauv ntau hom zuam. Muaj ntau qhov sib xws ntawm 50 -nucleotidase ntawm zuam thiab cov enzymes uas muaj nyob rau hauv vertebrates, thiab ib tug ntau yam ntawm putative functions yog ua los ntawm cov enzymes, nrog rau kev koom tes nyob rau hauv lub purine salvage txoj kev [108]. Ntawm cov zuam, pab pawg ntawm cov enzymes no muaj nyob hauv ntau cov ntaub so ntswg, xws li lub plab, cov qog ua kua qaub, thiab zes qe menyuam.

Txawm li cas los xij, lawv muaj ntau tshaj plaws hauv Malpighian tubules, tshwj xeeb tshaj yog nyob rau saum npoo ntawm Malpighian tubules thiab zes qe menyuam. Cov yam ntxwv ntawm 50 -nucleotidases qhia tias lawv yog lub hom phiaj rau cov tshuaj tiv thaiv kab mob [109]. Vam thiab al. tshawb xyuas 50 -nucleotidases rau lawv qhov muaj peev xwm koom nrog hauv kev txhaj tshuaj tiv thaiv tus tswv, thiab lawv pom tias kev txhaj tshuaj recombinant 50 -nucleotidase ib leeg hauv yaj ua rau muaj kev cuam tshuam tseem ceeb hauv cov tshuaj tiv thaiv nucleosidase, qhia tias lawv yuav yog cov tshuaj tiv thaiv zoo rau cov kev tsim tshuaj tiv thaiv [104].

Txawm li cas los xij, thaum tib pab pawg ntawm cov kws tshawb fawb soj ntsuam lawv cov haujlwm ua antigens hauv cov nyuj, tsis muaj qhov nce hauv cov tshuaj tiv thaiv kab mob. Yog li ntawd, 50 -nucleotidases tsis tau tshawb xyuas ntxiv ua antigens rau kev tsim tshuaj tiv thaiv. Txawm li cas los xij, kev tshawb fawb tsis ntev los no ua los ntawm lwm pab pawg kws tshawb fawb tau pom tias qib ntawm 50 -nucleotidase/apyrase ntau lawm nce hauv O. erraticus tom qab pub mis [110]. Tsis tas li ntawd, lawv tau hais tias thaiv kev ua haujlwm ntawm apyrase los ntawm kev txhaj tshuaj tiv thaiv tus tswv nrog cov protein apyrase recombinant tuaj yeem txo qis kev noj zaub mov hauv O. moubata zuam, ua kom pom tias 50 -nucleotidases/apyrases yog qhov muaj peev xwm cog lus rau cov neeg sib tw antigens rau kev loj hlob ntawm kev tiv thaiv zuam. tshuaj tiv thaiv [110,111].

Nucleotidase yog ib qho enzyme uas tuaj yeem ua rau cov tshuaj tiv thaiv hydrolysis ntawm nucleotides, rhuav tshem nucleotides rau hauv nucleosides thiab inorganic phosphates. Nucleotides muaj lub luag haujlwm tseem ceeb hauv cov kab mob hauv lub cev, suav nrog kev tsim kho, khaws cia, thiab xa mus rau DNA thiab RNA, kev hloov hluav taws xob, thiab kev hloov pauv ntawm tes. Yog li ntawd, nucleotidases ua lub luag haujlwm tseem ceeb hauv cov kab mob muaj sia. Kev tiv thaiv kab mob yog lub cev muaj peev xwm tiv thaiv kab mob nyob rau hauv ib puag ncig sab nraud, suav nrog ntau yam txheej txheem lom neeg, suav nrog kev nthuav dav, kev sib txawv, thiab kev tswj hwm ntawm lub cev tiv thaiv kab mob. Ntau qhov kev tshawb fawb tau pom tias nucleotidases tuaj yeem cuam tshuam rau kev ua haujlwm ntawm lub cev tiv thaiv kab mob thiab yog li kev tiv thaiv kab mob.

Piv txwv li, qee qhov sib txawv ntawm nucleotidases tau txuas rau kev txhim kho cov kab mob autoimmune. Tsis tas li ntawd, nucleotidase tuaj yeem cuam tshuam rau kev loj hlob thiab ua kom lub cev tiv thaiv kab mob, thiab txhawb kev ua haujlwm ntawm lub cev tiv thaiv kab mob. Yog li ntawd, muaj qee qhov kev sib raug zoo ntawm nucleotidase thiab kev tiv thaiv kab mob. Los ntawm qhov kev xav no, peb yuav tsum tau ua tib zoo saib xyuas kev txhim kho kev tiv thaiv. Cistanche muaj txiaj ntsig zoo rau kev txhim kho kev tiv thaiv. Nqaij tshauv muaj ntau yam khoom xyaw lom neeg, xws li polysaccharides, ob lub nceb, Huang Li, thiab lwm yam. Cov khoom xyaw no tuaj yeem txhawb kev tiv thaiv kab mob. Ntau hom cell hauv lub cev, ua kom lawv lub cev tiv thaiv kab mob.

Nyem cistanche tubulosa cov txiaj ntsig

2.5. Tick-Cement-Associated Antigen Cov neeg sib tw

Tick ​​cement yog ib qho sib xyaw ntawm glycol thiab lipoproteins secreted rau hauv tus tswv tsev ntawm zuam qaub ncaug sai tom qab txuas rau tus tswv tsev, thiab yog ib qho tseem ceeb ntawm zuam-derived antigens rau kev tsim tshuaj tiv thaiv [112]. Ntxiv nrog rau kev ua raws cov zuam lub qhov ncauj rau ntawm daim tawv nqaij ntawm tus tswv tsev [113], zuam cement tau pom tias ua tus depot rau B. burgdorferi sensu lato (sl) thiab tus kab mob zuam-borne encephalitis [114,115]. Txog tam sim no, ntau yam antigens tau raug txheeb xyuas thiab cim los ntawm zuam cement uas kuj tau pom tias muaj txiaj ntsig zoo hauv kev tswj cov zuam kab mob thiab zuam kab mob.

Truncated tsim ntawm 64P (64TRPs), 15 kDa cement protein secreted los ntawm cov qog qaub ncaug ntawm Rhipicephalus appendiculatus, pom kev tiv thaiv kev tiv thaiv kab mob Rhipicephalus sanguineus thiab Ixodes ricinus los ntawm kev tsom cov antigens nyob rau hauv nruab nrab lub plab thiab salivary qog nyob rau hauv cov neeg laus. Kev txhaj tshuaj tiv thaiv ntawm zuam-naïve hosts nrog recombinant 64P txo qis tus naj npawb ntawm nymphal thiab tus neeg laus zuam kab mob, ua rau 48 feem pua ​​nymphal thiab txog li 70 feem pua ​​​​ntawm cov neeg laus tuag, nrog rau qee qhov cuam tshuam ntawm qhov hnyav thiab qe qe ib yam nkaus [116].

Los ntawm cov txiaj ntsig no, nws zoo nkaus li tias cov protein no yog cov tshuaj tiv thaiv kab mob dav dav thiab muaj txiaj ntsig zoo rau cov neeg laus thiab tsis paub tab ntawm ntau hom zuam, suav nrog I. ricinus [100]. Cov cement antigen no tau ua haujlwm dual (i) ua cov tshuaj tiv thaiv hauv hamster, guinea npua, thiab luav qauv los ntawm kev cuam tshuam kev sib txuas thiab pub mis thiab (ii) los ntawm kev sib cuam tshuam nrog cov "ceev" midgut antigens, thaum kawg ua rau tuag ntawm cov zuam engorged. [100, 117]. Cov tshuaj tiv thaiv no tsis tsuas yog txhawb nqa cov tshuaj tiv thaiv kab mob titers hauv cov lus teb rau zuam kab mob tab sis kuj muaj kev sib cuam tshuam nrog cov zuam sib txawv; yog li ntawd, nws muab cov txiaj ntsig ntawm ob qho tib si "ceev" thiab "pom" antigens [118].

3. Hom tshuaj tiv thaiv kab mob

Ticks yog cov kab mob arthropod tshaj plaws uas pub rau tib neeg thiab tsiaj txhu thiab kis kab mob [19]. Cov kab mob Zoonotic suav txog ntau dua 60 feem pua ​​​​ntawm tag nrho cov kab mob sib kis cuam tshuam rau tib neeg, thiab nws kwv yees tias 22.8 feem pua ​​​​ntawm cov kab mob no kis los ntawm zuam vectors [131]. Kuj tseem muaj kev poob nyiaj txiag loj heev rau cov neeg ua liaj ua teb tsiaj txhu thoob ntiaj teb vim cov kab mob vectored los ntawm zuam uas cuam tshuam rau lawv cov tsiaj txhu [132,133].

Yog li ntawd, nws yog qhov tsim nyog los tswj cov zuam kom txo tau lub nra ntawm kev lag luam. Kev tswj cov zuam tau dhau los ua qhov nyuaj, vim cov zuam tuaj yeem txhim kho kev tiv thaiv rau cov khoom lag luam muaj acaricides [134-136]. Cov thev naus laus zis ntawm kev tswj hwm ib puag ncig zoo yog xav tau vim muaj kev txhawj xeeb txog kev nyab xeeb ntawm acaricides rau cov neeg ua haujlwm, zaub mov, thiab ib puag ncig thiab cov nqi nce ntxiv cuam tshuam nrog kev tshawb pom acaricide, kev tsim kho, thiab kev lag luam. Cov tshuaj tiv thaiv muaj ntau yam zoo dua li cov tshuaj acaricides vim lawv feem ntau tsis muaj tshuaj lom, tsis muaj kuab lom, thiab tsis tshua muaj nqi piv rau cov tshuaj.

Txawm li cas los xij, lawv feem ntau yog hom tshwj xeeb. Kev lag luam kws tshuaj tuaj yeem ua lub luag haujlwm tseem ceeb hauv kev txhawb nqa kev tshawb fawb los tsim cov tshuaj tiv thaiv uas tuaj yeem muab kev tiv thaiv siab tshaj plaws rau tus tswv tsev thiab muaj txiaj ntsig zoo rau ntau hom zuam [133,137]. Cov kev tshawb fawb tshuaj tiv thaiv tab tom tab tom ua hauv ntau lub teb chaws thiab cov seem ntawm tsab xov xwm no yuav tsom mus rau kev nce qib ntawm cov cuab yeej tshuaj tiv thaiv tshiab thiab ntawm cov uas twb muaj lawm (Daim duab 2).

Raws li kev siv tshuaj, tshuaj tiv thaiv tsis tuaj yeem tsis quav ntsej, thiab cov tshuaj tiv thaiv uas twb muaj lawm tuaj yeem hloov kho siv cov txheej txheem sib txuas thiab cov txheej txheem cloning kom cais cov antigens tshiab lossis hloov cov antigens uas twb muaj lawm los kho lawv cov txiaj ntsig. Nws kuj tseem tuaj yeem suav nrog ob lossis ntau dua cov tshuaj tiv thaiv tsis sib xws hauv ib qho tshuaj tiv thaiv ib yam khoom kom txo tau qhov kev pheej hmoo ntawm kev tiv thaiv kev txhim kho rau ib qho antigen lossis antigenic determinant.

3.1. DNA-raws li tshuaj tiv thaiv kab mob

Kev tsim cov tshuaj tiv thaiv DNA thiab nws siv tau ua rau muaj kev txhawj xeeb txog kev nyab xeeb; tshwj xeeb tshaj yog muaj peev xwm ntawm kev ruaj khov ntawm cov khoom siv noob caj noob ces (DNA) mus rau hauv cov kab mob somatic lossis txawm tias cov kab mob, uas yuav ua rau muaj kev hloov pauv ntawm cov noob thiab kev hloov pauv. Ib qho extrachromosomal plasmid-encoding luciferase vector tau kuaj pom hauv cov leeg pob txha rau ntau tshaj 19 lub hlis tom qab kev kho mob intramuscular (138). Tsis tas li ntawd, kev txhaj tshuaj intramuscular tom qab electroporation zoo heev ua rau tag nrho cov kab mob kis tau zoo. Kev sib xyaw chromosomal ntawm vector DNA ntawm qhov chaw random muaj feem cuam tshuam nrog kev nce ntxiv ntawm kev hloov pauv (139]. Raws li cov kev tshawb fawb no, qhov sib xyaw ua ke tau zoo hauv qab cov noob hloov pauv hloov pauv.

Txawm li cas los xij, Manam et al. pom tias feem ntau ntawm plasmid DNA muab rau hauv cov leeg pob txha ntawm cov nas sib txawv tseem nyob ntawm qhov chaw txhaj tshuaj. Cov feem me me kuj tau kuaj pom hauv cov gonads tab sis tsis tau muab tso rau hauv genome (140). Rov ua dua intramuscular daim ntawv thov ntawm luciferase-encoding reporter vector nyob rau hauv primates ua rau lub sij hawm ntev reporter qhia tab sis induced tsis muaj anti-DNA tshuaj tiv thaiv (141,142). Txawm li cas los xij, nws yuav tsum raug sau tseg tias cov lus hais saum toj no thiab kev txhawj xeeb ntxiv txog kev nyab xeeb ntsig txog cov tshuaj tiv thaiv DNA yuav tsum raug txiav txim siab txog lawv cov kev txhais lus rau hauv kev kho mob (143].

Ob xyoos dhau los, ntau pab pawg ntawm cov kws tshawb fawb tau tsom mus rau kev tsim cov tshuaj tiv thaiv DNA los tswj cov zuam kab mob, thiab txog tam sim no, ntau cov tshuaj tiv thaiv DNA tau raug qhia los tiv thaiv tus tswv (130,144,145). Cov tshuaj tiv thaiv DNA, uas txawv ntawm cov tshuaj tiv thaiv kab mob raws li cov tshuaj tiv thaiv ib txwm muaj raws li cov kab mob plasmids uas encode antigenic proteins, thiab cov ntaub ntawv sau tseg yog tswj los ntawm cov neeg txhawb nqa eukaryotic, muaj qhov zoo ntawm cov qauv tsim yooj yim, kev ruaj ntseg siab, thiab kev tswj xyuas kev nyab xeeb (143 ]. Hauv kev txhaj tshuaj DNA, cov tshuaj txhaj tshuaj plasmid DNA molecules tau xav tias yuav nkag mus rau hauv lub nucleus thiab nyob twj ywm nyob ntawd mus ib txhis li episomal DNA, tsim cov tshuaj tiv thaiv antigens tsis tu ncua ntev npaum li lub cell tseem ciaj sia (146). ib qho tshuaj tiv thaiv kab mob siab siab tuaj yeem daws tau los ntawm kev sib txuas txuas ntxiv, ua, thiab nthuav tawm cov tshuaj tiv thaiv rau T hlwb hauv vivo hauv cov tsiaj uas tau txhaj tshuaj DNA.

Tsis tas li ntawd, txij li cov tshuaj tiv thaiv DNA tsuas muaj plasmid DNA thiab tsis muaj cov kab mob sib kis, nws zoo nkaus li tias tau txais ntau yam tshuaj tiv thaiv lossis rov ua dua yuav tsis ua rau muaj kev tiv thaiv kab mob rau cov vector DNA (147). Cov tshuaj tiv thaiv tau nthuav tawm tuaj yeem nthuav tawm los ntawm MHC chav kawm I thiab cov complexes, uas tuaj yeem ua rau CD4 ntxiv thiab CD8 ntxiv rau T hlwb, txhawb kev tiv thaiv cellular thiab humoral, raws li (148].

Cov pov thawj los ntawm kev kawm ntawm De Rose li al. [144], nyob rau hauv uas Merino crossbred yaj tau txhaj tshuaj tiv thaiv B. micro ntxiv siv cov tshuaj tiv thaiv DNA. Thaum lub plasmid uas muaj tag nrho-ntev gene sequence ntawm Bm 86 tau muab ib leeg lossis nrog plasmid nqa cov noob qes rau cov cytokines, granulocyte-macrophage colony-stimulating factor (GM-CSF) lossis interleukin (IL) -1beta induced qib qis ntawm kev tiv thaiv tiv thaiv zuam tom ntej. Tsis tas li ntawd, kev txhaj tshuaj nrog Bm86 thiab GM-CSF plasmids ua rau muaj kev txo qis hauv cov zuam fertility. Hauv txhua pab pawg tau txhaj tshuaj tiv thaiv Bm86 DNA, cov tshuaj tiv thaiv kab mob tiv thaiv Bm86 tsawg. Tsis tas li ntawd, qib qis ntawm antigen tshwj xeeb stimulation ntawm peripheral ntshav lymphocytes tshwm sim hauv cov pab pawg no. Kev txhaj tshuaj DNA, txawm li cas los xij, ua rau muaj cov tshuaj tiv thaiv kab mob tom qab muaj zog tom qab ib qho kev txhaj tshuaj ntawm Bm recombinant 86 protein nyob rau hauv adjuvant. Kev tsim cov tshuaj tiv thaiv kab mob, txawm li cas los xij, tau tshwm sim me ntsis zoo dua li tom qab ob koob tshuaj tiv thaiv nrog cov protein sib xyaw.

Tsis tas li ntawd, ntau lwm tus kws tshawb fawb tau tshawb xyuas qhov ua tau zoo ntawm DNA-raws li antigens los tiv thaiv cov tswv ntawm cov zuam kab mob. Piv txwv li, Sayed et al. [149] rho tawm DNA los ntawm Argas persicus qe thiab siv nws los tiv thaiv qaib nrog koob tshuaj ntawm 200-800 µg DNA / kg nqaij qaib lub cev hnyav. Cov txiaj ntsig tau txhawb nqa, vim tias kev noj zaub mov zoo ntawm cov zuam raug txo los ntawm 74.64 feem pua ​​(50 µg DNA / kg qaib lub cev hnyav) thiab 89.39 feem pua ​​(100 µg DNA / kg nqaij qaib lub cev hnyav) thaum lawv raug DNA-tiv thaiv qaib. Tsis tas li ntawd, cov kws sau ntawv tau tshaj tawm tias cov ntshav ntawm qaib cov tshuaj tiv thaiv DNA muaj kev ua haujlwm tiv thaiv lub plab proteins ntawm A. precious; Txawm li cas los xij, kev tshuaj xyuas ntxiv siv lwm hom zuam qhia tau hais tias kev ua haujlwm hauv cov ntshav yog hom tshwj xeeb. Cov qauv electrophoretic ntawm cov tshuaj tiv thaiv kab mob nqaij qaib tau pom peb cov protein tshiab, uas tau xav tias yuav koom nrog hauv kev txhim kho kev tiv thaiv kab mob ntawm cov qaib tiv thaiv zuam [149]. Tom qab ntawd, ntau cov kev tshawb fawb tsom rau kev txhaj tshuaj tiv thaiv kab mob DNA tshwj xeeb; Txawm li cas los xij, lawv qib kev tiv thaiv txawv nrog ntau hom antigens. Nws tau pom tias BALB/c nas txhaj nrog Plasmid pBMC2-encoding antigen Bm{15}} pom tias tiv thaiv Boophilus microplus.

Kev txhaj tshuaj ntau dua ntawm kev txhaj tshuaj tiv thaiv kab mob Anti-Bm86 tshuaj tiv thaiv kab mob thiab ntau dua interleukin (IL) qib (IL-4, IL-5, thiab IL-12 (p40)) thiab interferon-gamma (IFN-) qib hauv sera ntawm nas txhaj tshuaj nrog pBMC2. Cov nas txhaj tshuaj nrog pBMC2 tau pom cov tshuaj tiv thaiv kab mob tshwj xeeb ntawm splenocytes raws li kev koom ua ke ntawm bromodeoxyuridine thiab IFN g secretion. Kev siv cov tshuaj tiv thaiv no hauv cov tsiaj txhu ua rau muaj cov tshuaj tiv thaiv kab mob, qhia tias Bm86 tshuaj tiv thaiv DNA ua rau muaj zog tiv thaiv kab mob tiv thaiv B. micro plus [150]. Lwm txoj kev tshawb fawb tau soj ntsuam lub cev tiv thaiv kab mob elicited los ntawm recombinant plasmids encoding Paramyosin (Pmy) ntawm H. longicornis (pcDNA3.1 (ntxiv rau )-Pmy) hauv luav. Cov luav tau tsim muaj qib siab ntawm IgG, qhia tias kev tiv thaiv kab mob humoral raug ntxias los ntawm kev txhaj tshuaj. Qee cov zuam (27.31 feem pua) uas pub rau cov tshuaj tiv thaiv kab mob luav tuag, qhov seem ntawm cov zuam 'qhov nruab nrab qhov hnyav thiab qhov oviposition ntawm cov poj niam laus raug txo los ntawm 36 thiab 39 feem pua.

Yog li, nws zoo nkaus li tias cov tshuaj tiv thaiv Pmy DNA tuaj yeem ua rau muaj txiaj ntsig zoo rau lub cev tiv thaiv kab mob txawm li cas los xij nws tau muab thiab tiv thaiv ib feem ntawm cov kab mob H. longicornis [151]. Interestingly, ib tug multi-epitope DNA tshuaj tiv thaiv incorporating ob CD4 ntxiv thiab CD8 ntxiv rau cytotoxic T lymphocyte epitopes muab 100 feem pua ​​kev tiv thaiv rau yaj nyob rau hauv lub chaw kuaj mob tiv thaiv Ehrlichia ruminantium. Txawm li cas los xij, cov txiaj ntsig tsis tau rov ua dua raws li thaj chaw. Nyob rau hauv txoj kev tshawb no, pLamp kev koom tes nrog MPL ntawm txoj kev intramuscular, ntxiv rau cov tshuaj pleev ib ce, tiv thaiv cov yaj txog li 60 feem pua ​​​​ntawm cov zuam los ntawm inducing activation ntawm lub cim xeeb T cell teb [152].

Ob peb lwm cov tshuaj tiv thaiv, xws li Salp14 thiab lipocalins, ib leeg lossis ua ke nrog lwm cov antigens tsis ntev los no tau raug soj ntsuam raws li cov tshuaj tiv thaiv DNA, uas ntxiv kev cia siab los tsim cov tshuaj tiv thaiv DNA tiv thaiv zuam [130,153]. Nws tau pom tias salp14 DNA tshuaj tiv thaiv-elicited erythema ntawm qhov chaw zuam tom qab kev sib tw zuam [153]. Ib yam li ntawd, ib qho tshuaj tiv thaiv lipocalins (LIP) uas suav nrog cov plasmid pcDNA3 recombinant. Txawm hais tias daim ntawv thov no ua rau muaj kev tsis txaus siab ntawm tus tswv tsev thiab tseem cuam tshuam rau qhov hnyav, oviposition, thiab hatchability ntawm H. longicornis, qhov ua tau zoo tsawg dhau, qhia tias cov tshuaj tiv thaiv no tsis haum rau cov tshuaj tiv thaiv vim nws muab kev tiv thaiv ib nrab rau tus tswv tsev [130 ].

Thaum kawg, lub hom phiaj tseem ceeb ntawm kev tsim cov tshuaj tiv thaiv DNA yuav tsum yog los tsim cov tshuaj tiv thaiv nyob rau hauv ib txoj kev uas nws polarizes lub cev tiv thaiv kab mob ntawm tus tswv tsev rau Th2 teb vim hais tias cov tshuaj tiv thaiv humoral ua lub luag haujlwm tseem ceeb hauv kev tiv thaiv zuam. Hauv cov nyuj uas tau txhaj tshuaj tiv thaiv kab mob B. micro ntxiv rau midgut antigens, cov theem ntawm IgG1 tshwj xeeb, uas tau hloov kho los ntawm Th2 hlwb, tau pom muaj kev cuam tshuam nrog kev tiv thaiv. Muaj qhov ua tau tias yog tias cov cim qhia zais cia tau muab tso rau hauv qab ntawm lub hom phiaj gene, tom qab ntawd lub hom phiaj antigen tuaj yeem tso tawm mus rau hauv cov khoom siv sab nraud thiab ua rau muaj kev lom zem ntau dua. Nws kuj tseem yog qhov kev xaiv ntawm Th2 hlwb yuav nyiam yog tias lawv tau koom nrog lwm cov tshuaj tiv thaiv kab mob xws li IL4 thiab IL10.

3.2. mRNA tshuaj tiv thaiv

Nyob rau hauv xyoo tas los no, ntau qhov kev sim tau ua kom pom cov tshuaj tiv thaiv tshiab uas tuaj yeem siv rau hauv kev tsim cov tshuaj tiv thaiv kab mob, nrog rau kev txhim kho ntau heev. Txhawm rau ntsuas qhov ua tau zoo ntawm cov neeg sib tw tshuaj tiv thaiv, cov protein sib xyaw ua ke, tsis hais seb lawv puas cuam tshuam nrog lwm cov proteins lossis adjuvants, tau yog lub platform ntawm kev xaiv rau kev sim lawv cov kev ua tau zoo los ntawm kev siv cov qauv kab mob.

Vim qhov yooj yim uas DNA thiab mRNA tshuaj tiv thaiv platforms tuaj yeem tsim tau, tau muaj kev txhim kho tseem ceeb hauv kev siv tshuaj tiv thaiv kab mob (DNA thiab mRNA) platforms hauv xyoo tas los [130,145]. Ib qho tshuaj tiv thaiv mRNA encoding ib tug cocktail ntawm zuam salivary proteins ntxias "tick immunity" nyob rau hauv guinea npua, yog li no remarkably txo tau tus kab mob ntawm zuam-borne Borrelia burgdorferi, tus ua rau tus kab mob Lyme (borreliosis). Txawm hais tias muaj ntau tus zuam antigen neeg sib tw tau ua pov thawj los txhawb kev tiv thaiv kab mob hauv ib tus tswv tsev, nws tseem tsis tau muaj peev xwm rov ua dua cov zuam tiv thaiv kab mob uas siv tshuaj tiv thaiv. Muaj qhov ua tau tias qhov no yuav yog vim tias, nyob rau theem sib txawv ntawm kev pub mis, muaj pes tsawg leeg ntawm salivary proteins hauv cov zuam tuaj yeem hloov pauv hloov pauv, muaj peev xwm tswj hwm tus tswv tsev hloov pauv. Cov ntaub ntawv no tau muab nyob rau hauv ib txoj kev tshawb fawb tsis ntev los no, uas ib pab pawg neeg tshawb fawb tau txheeb xyuas thiab xaiv 19 cov kua qaub proteins ntawm cov zuam dub-legged I. scapularis, uas yog ib qho kab mob rau cov kab mob Lyme hauv tib neeg. Lawv engineered nucleoside-hloov mRNAs uas encode cov proteins no.

Txhawm rau tsim cov tshuaj tiv thaiv mRNA-LNP 19ISP (19 Ixodes salivary proteins), cov no tau ntim rau hauv qhov sib npaug ntawm cov lipid nanoparticles (LNPs). Txhawm rau ntsuas qhov cuam tshuam ntawm cov tshuaj tiv thaiv ntawm tus cwj pwm pub mis ntawm I. scapularis, guinea npua tau txhaj tshuaj intradermally peb zaug hauv 4- lub lis piam ib ntus, uas ua rau muaj cov tshuaj tiv thaiv zoo rau yam tsawg kawg kaum ntawm cov tshuaj tiv thaiv kab mob. Hauv cov kauj ruam tom ntej ntawm qhov kev sim, cov tsiaj tau sib tw nrog cov tsis muaj kab mob I. scapularis nymphs. Cov tsiaj uas tau txhaj tshuaj tiv thaiv kab mob erythema loj heev hauv 24 teev.

Tsis tas li ntawd, cov zuam ntawm cov tsiaj uas tau txhaj tshuaj tsis zoo thiab pib tshem tawm los ntawm 48 teev, nrog 80 feem pua ​​​​ntawm cov zuam tshem tawm ntawm cov tsiaj uas tau txhaj tshuaj tom qab 96 teev, piv nrog 20 feem pua ​​​​ntawm cov tsiaj uas tsis tau txhaj tshuaj. Txhawm rau tshuaj xyuas ntxiv seb qhov hloov pauv tus cwj pwm pub mis puas cuam tshuam rau kev sib kis ntawm cov kab mob, B. burgdorferi-infected I. scapularis nymphs tau muab tso rau ntawm guinea npua uas tau txhaj tshuaj nrog 19ISP lossis nrog mRNA tshuaj tiv thaiv encoding firefly luciferase. Txhua tus tsiaj no tau txais peb tus zuam uas tau kis tus kabmob. Xav tias tib neeg yuav tshem tau cov zuam uas ua rau khaus khaus khaus, cov zuam raug tshem tawm hauv ob qhov muag tsis pom kev sai li sai tau thaum liab tshwm.

Tag nrho ntawm 46 feem pua ​​​​ntawm cov tsiaj tswj tau kis tus kab mob B. burgdorferi peb lub lis piam tom qab qhov kev sib tw, qhov twg tsis muaj cov tsiaj uas tau txhaj tshuaj tiv thaiv kab mob no. Kev tshuaj ntsuam gene qhia tau pom tias cov tshuaj tiv thaiv tau qhib ntau txoj hauv kev tiv thaiv kab mob, suav nrog T thiab B cell receptors, chemokine, FcεRI, thiab IL-17 signaling, nrog rau cov tshuaj tua kab mob ntawm tes-mediated toxicity. Tsis tas li ntawd, kev tshuaj xyuas tom tsev kuj tau pom tias cov tshuaj tiv thaiv tau ua rau cov lus teb T-cell [154].

Tib lub sijhawm, tib pab pawg ntawm cov kws tshawb fawb tau siv Salp14 ua tus qauv antigen los tshuaj xyuas zuam tiv thaiv kab mob siv mRNA lipid nanoparticles (LNPs), plasmid DNA, los yog recombinant protein platforms [153]. Hauv txoj kev tshawb no, kev txhaj tshuaj tiv thaiv suav nrog cov nucleoside-hloov mRNA lipid nanoparticles encoding (mRNA-LNPs) Salp14 tau xa mus rau intradermally, nrog ob qho kev txhawb nqa txhua 4 lub lis piam. Txoj kev loj hlob ntawm Salp14- cov tshuaj tiv thaiv tshwj xeeb tau muab piv nrog cov tswv yim sib txawv ntawm kev txhaj tshuaj. Salp14 mRNA txhaj tshuaj tiv thaiv yog lub platform uas induced lub zog humoral teb piv rau DNA thiab protein txhaj tshuaj. Guinea npua txhaj tshuaj tiv thaiv nrog salp14 mRNA elicited lub zog tshaj plaws, thiab khaus erythema pom ntawm qhov chaw tom hauv txhua pawg txhaj tshuaj; Txawm li cas los xij, nws tsis cuam tshuam tus nqi ntawm zuam detachment thiab tsis hloov qhov hnyav hnyav [153]. Cov tshuaj tiv thaiv zuam yuav tsum ua kom erythema ua tau zoo, thiab ib txoj hauv kev los hloov tom qab ntawm kev noj cov zuam, nrog rau kev sib txuas thiab kev sib koom ua ke, yog siv cov tshuaj tiv thaiv uas muaj ntau cov kab mob qaub ncaug antigens [154].

Yog li ntawd, nws zoo nkaus li kev txhaj tshuaj nrog nucleoside-hloov mRNALNP salp14, uas tuaj yeem siv los ua cov tshuaj tiv thaiv muaj peev xwm, tuaj yeem ua rau cov tshuaj tiv thaiv kab mob siab dua thiab ua ntej thiab qib siab dua ntawm kev txhaj tshuaj nrog DNA lossis protein, uas qhia tias Salp14 tuaj yeem ua tau. ua tus neeg sib tw zoo rau cov tshuaj tiv thaiv, ib leeg nrog kev ua kom zoo lossis ua ke nrog lwm tus neeg sib tw antigens [154].

Ntawm qhov tod tes, nws zoo nkaus li tias ntau hom tshuaj tiv thaiv mRNA tuaj yeem muaj peev xwm tshem tau cov zuam tiv thaiv hauv cov tsiaj txhu xws li guinea npua thiab tiv thaiv zuam kab mob thiab zuam-yug, tej zaum los ntawm kev txwv lub sij hawm ntev ntawm zuam noj rau lawv tus tswv tsev. Nws kuj tau hais tias ib qho mRNA-LNP formulation uas ua rau qeeb, txuas ntxiv cov tshuaj tiv thaiv kab mob, tuaj yeem ua raws li cov zuam tom. Yog tias lub tswv yim no tuaj yeem txhais rau tib neeg, nws yuav yog thawj cov tshuaj tiv thaiv uas tsis ncaj qha rau cov kab mob lossis kab mob microbial, tab sis hloov nws cov vector. Tsis tas li ntawd, txij li cov tshuaj tiv thaiv kab mob tseem tab tom tsim los pab tib neeg hauv kev tiv thaiv kev sib kis ntawm zuam kab mob, lub tswv yim ntawm kev txhaj tshuaj tiv thaiv thiab kev xaiv cov tshuaj tiv thaiv antigens yuav tsum tau muab coj los xav.

3.3. Protein-based Vaccines

Qee cov tshuaj tiv thaiv uas muaj protein ntau yog muag thiab siv tau. Ib txoj haujlwm tshuaj tiv thaiv tau pib ua ntej xyoo 1970 thaum cov kws tshawb fawb pib sim nrog ob hom tshuaj tiv thaiv kab mob los tiv thaiv tus tswv tsev tiv thaiv tus zuam (D. Anderson) thaum lub sijhawm. Thawj suav nrog cov tshuaj antigens tau los ntawm lub plab thiab zes qe menyuam, thaum lub thib ob suav nrog tag nrho cov khoom nruab nrog cev tau muab rho tawm los ntawm cov poj niam semi-engorged D. Anderson.

Txoj kev tshawb no tau tshawb pom tias cov tshuaj tiv thaiv kab mob sib kis tau ua rau lub cev tiv thaiv kab mob qog nqaij hlav thaum cov tsiaj nyeg yog inoculated nrog cov extracts tau los ntawm cov neeg laus R. microplus poj niam [155]. Qhov kev tshawb nrhiav thawj zaug no los ntsuas qhov ua tau zoo ntawm kev tsim tshuaj tiv thaiv tau txhawb cov kws tshawb fawb thoob plaws ntiaj teb kom tsom mus rau kev tsim cov tshuaj tiv thaiv rau kev tswj cov zuam thiab zuam-yug kab mob. Yog li, nyob rau xyoo 1980, ob pawg neeg tshawb nrhiav tau ua thawj qhov kev tshawb fawb tshawb fawb siv cov tshuaj tiv thaiv los tshuaj xyuas lub cev tiv thaiv kab mob ntawm bovines tawm tsam R. microplus [156].

Ua raws li cov kev tshawb fawb saum toj no, nws tau pom tias cov zuam plab-txuas nrog glycoprotein tuaj yeem ua rau muaj kev tiv thaiv kab mob hauv tus tswv [157]. Hauv kev tshawb fawb tom qab, tib pab pawg tshawb fawb tau cais cov glycoprotein nrog qhov hnyav ntawm 89 kDa, uas tau hu ua Bm86 thiab tau tshaj tawm tias muaj feem cuam tshuam nrog lub plab hlwb ntawm R. microplus [158,159]. Bm 86 recombinant protein tau tsim nyob rau hauv ib tug loj scale siv ib tug poov xab qhia system.

Txog tam sim no, tsuas yog Bm86- cov tshuaj tiv thaiv raws li kev lag luam nrog cov npe sib txawv, piv txwv li, nws tau muag hauv Australia nrog TickGARD® lub npe hom thiab hauv tebchaws Cuba hauv qab Gavac® [160,161]. Cov tshuaj tiv thaiv no feem ntau siv nyob rau hauv ntau lub teb chaws los txo cov zuam siab ntawm nyuj. Nws tau pom tias kev siv cov tshuaj tiv thaiv no tuaj yeem txo cov zuam cov pej xeem txog li 74 feem pua ​​​​thiab lawv cov kev ua tau zoo tag nrho ntawm 51 feem pua ​​​​rau 91 feem pua ​​​​, uas txawv nrog cov zuam cov pej xeem thiab kev noj haus ntawm cov nyuj [160–163]. Muaj pov thawj tias qee tus Columbian, Mexican, thiab Brazilian R. micro ntxiv rau cov zuam kab mob pom tias muaj kev ua haujlwm qis dua piv rau Cuban thiab Australian R. micro ntxiv rau cov zuam, thiab txawm tias Argentinian R. micro ntxiv rau hom A zoo li tiv thaiv kev txhaj tshuaj nrog. Bm86 [34,164]. Kev tshuaj xyuas ntxiv tau ua los ntawm qhov sib txawv ntawm qhov ua tau zoo ntawm Bm86 tshuaj tiv thaiv rau cov neeg ntawm tib hom zuam nyob rau ntau qhov chaw ntawm lub ntiaj teb, thiab nws tau txiav txim siab tias cov neeg sib txawv ntawm cov zuam feem ntau yuav muaj ntau hom kab mob hauv Bm{ {12}} antigen noob nyob rau hauv cov nqe lus ntawm cov amino acid ib theem zuj zus ntawm cov noob, thiab qhov no yog lub ntsiab yog vim li cas uas twb muaj lawm Bm 86- cov tshuaj tiv thaiv raws li tsis zoo li.

Piv txwv li, muaj ib tug polymorphism nyob rau hauv cov noob homologous rau Bm86 (tsim raws li Bm95) txheeb xyuas nyob rau hauv zuam pej xeem nyob rau hauv Argentina, uas ua rau muaj kev sib txawv nyob rau hauv ib theem ntawm Bm 86 ntawm zuam cov neeg xws li cov pom nyob rau hauv teb chaws Cuba thiab Australia, uas tej zaum yuav piav qhia yog vim li cas cov tshuaj tiv thaiv Bm 86 tsis zoo li Argentine zuam [34]. Xav txog cov teeb meem tiv thaiv ntawm Bm86 tshuaj tiv thaiv, cov kws tshawb fawb tau tsim cov tshuaj tiv thaiv Bm95 rov ua dua uas tau ua pov thawj tias muaj txiaj ntsig zoo, nrog rau tag nrho cov txiaj ntsig ntawm 89 feem pua ​​​​hauv tebchaws Cuba thiab Argentina thiab 81 feem pua ​​​​hauv Is Nrias teb hais txog kev txo cov zuam kab mob. [34, 102, 120, 165].

Dhau li ntawm cov tshuaj tiv thaiv kev lag luam hais saum toj no thiab nws qhov kev sim ua tau zoo, ntau lwm cov kev tshawb fawb tau tsom mus rau kev txhim kho kev ua tau zoo ntawm Bm86- raws li cov tshuaj tiv thaiv. Qee qhov kev tshawb fawb tsis ntev los no tau tsim cov peptides, suav nrog SBm4912, SBm7462®, thiab SBm19733, uas tau los ntawm Bm86, thiab kuj tau tsim ib qho rSBm7462® recombinant peptide, thiab tshuaj xyuas lawv cov txiaj ntsig. Qhov feem pua ​​​​ntawm cov peptides no muaj li ntawm 35.87 feem pua ​​​​rau 81.05 feem pua ​​​​, qhia tias cov peptides no, tshwj xeeb, SBm7462® thiab rSBm7462®, ua lub luag haujlwm tseem ceeb hauv kev tiv thaiv tus tswv tsev thiab tuaj yeem ua lag luam vim lawv muaj txiaj ntsig zoo ntawm kev txo cov zuam. kab mob [121,122]. Tsis tas li ntawd, txhawm rau txhim kho Bm86 cov tshuaj tiv thaiv kab mob sib xyaw ua ke, tsis ntev los no, Lapisa SA tau qhia txog Bm86- tshuaj tiv thaiv Bovimune Ixovac® hauv Mexico. Txawm li cas los xij, cov tshuaj tiv thaiv no tsis tau kawm txog nws cov txiaj ntsig tiv thaiv zuam; Yog li ntawd, cov kev tshawb fawb yuav tsum tau txiav txim siab nws cov teebmeem ntawm cov zuam sib txawv los txiav txim seb nws ua tau zoo.

Bm86 tshuaj tiv thaiv homolog-raws li (TickGard) zoo nkaus li tsim nyog, vim tias cov tshuaj tiv thaiv no muaj daim ntawv thov dav thiab tuaj yeem ua rau cov tshuaj tiv thaiv kab mob sib kis hauv ntau hom zuam, xws li Rhipicephalus sanguineus, Hyalomma anatolicum anatolicum, Rhipicephalus (Boophilus ) decoloratus, Rhipicephalus (Boophilus) annulatus, thiab Hyalomma dromedary [166–168]. Txawm li cas los xij, cov tshuaj tiv thaiv no tsis tuaj yeem ua rau muaj kev tiv thaiv kev tiv thaiv kab mob hauv qee hom zuam (xws li Rhipicephalus appendiculatus, Amblyomma variegatum, thiab Amblyomma cajennense) [169,170]. Nws yog qhov nthuav kom nco ntsoov tias cov tshuaj tiv thaiv Bm86 muaj 100 feem pua ​​​​ntawm cov tshuaj tiv thaiv R. annulatus, uas ua rau muaj kev ua tau zoo dua li qhov qhia txog kev ua tau zoo ntawm cov tshuaj tiv thaiv homologous nrog R. microplus. Yog vim li cas rau qhov no tej zaum yuav yog vim lub physiological yam (xws li, tsawg dua ntshav engorgement thiab qis dua cov protease kev ua si nyob rau hauv lub cev) los yog zuam genetic yam. Cov xwm txheej no tuaj yeem cuam tshuam rau BM{10}} qib protein lossis zuam cov txheej txheem physiological xws li kev noj zaub mov thiab protein degradation, ua rau muaj txiaj ntsig zoo dua antibody-antigen kev sib cuam tshuam [171]. Bm86 txhaj tshuaj tiv thaiv zoo tiv thaiv kab mob R. microplus zuam, tab sis nws nyuaj rau kev nthuav tawm cov kev paub dhau los no rau cov tshuaj tiv thaiv kab mob Ixodes zuam.

Nyob rau hauv sib piv rau I. ricinus thiab I. scapularis, R. microplus yog ib tug tswv tsev zuam uas pub tsuas yog rau nyuj [168]. Nws kuj muaj lub neej luv luv, tsis molt, thiab nrhiav tau tus tswv tsev tshiab thaum cov ntshav noj mov tiav. Qhov kev ua tau zoo ntawm cov tshuaj tiv thaiv Bm86 tau tshawb xyuas hauv cov nyuj uas tau kis rau R. microplus zuam larvae, thiab kev ntsuas tau ua los ntawm qhov tsis muaj feem cuam tshuam txog kev tiv thaiv zuam ntawm cov poj niam laus uas tau tso tseg tom qab txhaj tshuaj tiv thaiv. Yog li, kev ntsuas kev tiv thaiv yog qhov suav ntawm kev cuam tshuam ntawm ob lub sijhawm molting thiab peb theem zuam. Nws tau raug qhia rau R. microplus tias Bm86 txhaj tshuaj tiv thaiv ua rau muaj kev puas tsuaj thiab tom qab ntawd txo qhov hnyav ntawm cov poj niam laus cov zuam [172]; Txawm li cas los xij, qhov txheeb ze cuam tshuam ntawm Bm86 txhaj tshuaj tiv thaiv ntawm lub neej tsis paub tab ntawm R. microplus tsis paub meej. Bm86 homologs kuj tau raug cais tawm thiab txheeb xyuas los ntawm cov zuam Ixodes. I. ricinus muaj ob homologs ntawm Bm86, Ir86-1, thiab Ir-86-2, thiab I. scapularis kuj muaj ob homologs ntawm Is86-1 thiab Is{{10} } [173] ib. Ib txoj kev tshawb fawb tom ntej tau tshawb pom tias kev txhaj tshuaj tiv thaiv kab mob sib xyaw ua ke ntawm Ir86 cov proteins txhim kho cov ntshav IgG titers tiv thaiv cov tshuaj recombinant Ir{13}} proteins; Txawm li cas los xij, cov tshuaj tiv thaiv tsis muaj peev xwm tiv thaiv cov luav tawm tsam I. ricinus kev sib tw; tsis yog tus lej ntawm cov zuam txuas los yog zuam hnyav tau txo qis [174].

Yog li ntawd, kev txhaj tshuaj tiv thaiv Bm86 homologs hauv Ixodes tsis suav tias yog ib txoj hauv kev zoo los tswj cov neeg Ixodes ricinus, txawm tias Bm86 txhaj tshuaj tiv thaiv muaj txiaj ntsig zoo rau R. microplus. Txawm hais tias Bm 86 tshuaj tiv thaiv tau pom tias muaj kev vam meej, nws yog ib qho tseem ceeb kom nkag siab tias cov tshuaj tiv thaiv tsis zoo li yuav hloov cov tshuaj acaricides vim nws tsis muaj "knock-out effect" cuam tshuam nrog acaricides. Txawm li cas los xij, qhov kev paub dhau los tau pom tias kev siv Bm86 txo qis qhov xav tau ntawm kev siv tshuaj acaricide hauv thaj teb. Piv txwv li, Cuba txoj cai nruj ntawm nws qhov kev tswj xyuas zuam ua rau txo qis ntawm cov tshuaj acaricide siv hauv lub tebchaws los ntawm 87 feem pua, uas yog piv rau cov txiaj ntsig ntawm kev tshawb fawb tsis ntev los no hauv Venezuela [161,175,176].

Tsis tas li ntawd, kev siv tshuaj tiv thaiv Bm 86 kuj tseem txo qis cov kab mob ticborne, suav nrog Bovine anaplasmosis thiab Bovine babesiosis. Daim ntawv thov ntawm cov tshuaj tiv thaiv no kuj tau txhim kho cov khoom tsim tau ntawm cov tsiaj nyeg, piv txwv li, nyuj, thiab thiaj li txo cov nyiaj txiag poob ntawm cov neeg ua liaj ua teb [160]. Cov yam ntxwv saum toj no ntawm Bm86 txhaj tshuaj tiv thaiv qhia tau tias nws yog ib txoj hauv kev siv nyiaj ntau dua piv rau kev siv tshuaj lom neeg hauv kev cuam tshuam nrog zuam kab mob. Yog li ntawd, cov tshuaj tiv thaiv no tuaj yeem ua pov thawj tias muaj txiaj ntsig zoo hauv kev txo cov zuam kab mob nrog rau kev txhim kho kev tswj cov zuam tawm ntawm cov tsiaj txhu ua liaj ua teb kom txo cov zuam los ntawm cov kab mob.

4. Cov lus xaus

Ticks pub ntshav rau kev loj hlob, kev loj hlob, thiab kev yug me nyuam, thiab lawv muaj lub luag haujlwm rau kev sib kis ntawm ntau yam zuam-yug kab mob. Ixodes zuam, piv txwv li, kis ntau tus kab mob, suav nrog cov kab mob, protozoa, thiab kab mob. Nws yog ib qho tseem ceeb uas yuav tsum nco ntsoov tias cov tshuaj tiv thaiv kab mob txo cov zuam kab mob thiab tiv thaiv kab mob sib kis, thiab ntxiv rau kev nyab xeeb dua li kev tswj hwm tshuaj, uas yuav muaj kev phiv tsis zoo. Ob peb cov antigens tshiab los ntawm ntau cov ntaub so ntswg / kab mob tau raug txheeb xyuas thiab lawv cov txiaj ntsig tau raug tshuaj xyuas hauv cov tsiaj txhu, uas tau ua rau muaj kev vam meej tseem ceeb rau kev tsim cov tshuaj tiv thaiv kab mob ticks uas tsis muaj kev phiv tshwm sim. Cov tshuaj tiv thaiv raws li Bm86 cov protein tau raug muag hauv ntau lub tebchaws, thiab lawv cov kev siv tshuaj tiv thaiv R. microplus tau qhia tias kev txhaj tshuaj tiv thaiv cov zuam tuaj yeem siv tau zoo. Txawm li cas los xij, Bm86-cov tshuaj tiv thaiv tsis zoo sib npaug rau lwm hom zuam, xws li cov zuam Ixodes. Nws tau pom tias kev txhaj tshuaj nrog Bm86 homolog ntawm I. ricinus tsis muaj kev cuam tshuam rau kev noj zuam [174].

Tsis tas li ntawd, vim hais tias R. micro ntxiv tsuas yog pub rau ib tus tswv tsev xwb, cov larvae tau siv los tawm tsam cov nyuj, uas ua rau cov poj niam laus tag nrho cov zuam, uas tsis tsuas yog txo cov zuam xwb tab sis kuj muaj kev cuam tshuam loj rau tag nrho peb theem ntawm lub neej. zuam. Nyob rau hauv sib piv rau R. microplus, Ixodes zuam hloov hosts thoob plaws hauv lawv lub neej voj voog thiab yog li ntawd Ixodes zuam txhaj tshuaj yuav tsum muaj kev tiv thaiv zoo ntawm kev sib txuas thiab / los yog pub cov zuam thaum lub sij hawm noj ntshav ntawm ib tus tswv tsev. Txawm li cas los xij, kev txhaj tshuaj tiv thaiv kab mob Ixodes zoo li ua tau thiab muaj tseeb. Nws yog ib qho tseem ceeb uas yuav tsum nco ntsoov tias kev tiv thaiv tus tswv tsev tuaj yeem ua haujlwm nyuaj nrog hom tshuaj tiv thaiv no. Muaj qee qhov lwm cov proteins, ntxiv rau Bm 86, uas kuj tseem muaj peev xwm kho tau raws li cov tshuaj tiv thaiv kab mob lossis tshuaj tiv thaiv kab mob [39,61].

Kev nce qib tsis ntev los no hauv genomics thiab proteomics tau ua rau peb tshawb pom cov antigens tshiab thiab siv cov txheej txheem molecular los tswj cov proteins uas tau txheeb xyuas thiab kuaj cov tshuaj tiv thaiv tshiab tau nrawm dua thiab raug nqi ntau dua li yav dhau los. Kev txhaj tshuaj DNA kuj yog ib qho kev xaiv zoo heev; Txawm li cas los xij, feem ntau, hom kev txhaj tshuaj no tsuas tuaj yeem ua rau qis qis ntawm cov tshuaj tiv thaiv antigen thiab txwv tsis pub muaj cov tshuaj tiv thaiv kab mob uas ua rau CD4 ntxiv rau T pab hlwb ntawm MHC chav kawm II txoj hauv kev [177]. Txawm li cas los xij, kev txhaj tshuaj DNA tsis yog tsuas yog muab kev tiv thaiv tseem ceeb rau tus tswv tsev tab sis kuj tau txiav txim siab los muab kev tiv thaiv kev tiv thaiv kab mob yog tias nws tau ua raws li cov tshuaj tiv thaiv kab mob los yog tshuaj tiv thaiv kab mob sib xyaw ua ke [178].

Tsis tas li ntawd, mRNA-LNPs tuaj yeem pab txhawm rau tshem tawm erythema ntawm qhov chaw zuam tom, uas yog ib qho tseem ceeb tshaj plaws thaum ntxov qhia txog kev tiv thaiv zuam. mRNA-LNPs uas muaj zuam noob yog lub platform muaj txiaj ntsig rau kev tsim cov tshuaj tiv thaiv uas tuaj yeem tiv thaiv cov kab mob uas tau xaiv los ntawm zuam [153,154]. Ob qho tshuaj tiv thaiv DNA thiab mRNA kuj zoo li yog cov tswv yim zoo thiab muaj kev cia siab yav tom ntej tias kev txhaj tshuaj mRNA lossis DNA rau kev tswj cov zuam kab mob thiab zuam-yug kab mob yuav raug tsim thiab tseem muab kev tiv thaiv hla. Txawm li cas los xij, txog tam sim no tsis muaj tshuaj tiv thaiv tau ua lag luam, qhia tias yuav tsum muaj kev tshawb fawb ntxiv los txiav txim siab qhov ua tau zoo ntawm cov tshuaj tiv thaiv ntau ntxiv rau lawv siv los tsim cov tshuaj tiv thaiv DNA lossis mRNA. Kev txheeb xyuas thiab ua tus cwj pwm ntawm cov tshuaj tiv thaiv kab mob tshiab tuaj yeem tiv thaiv kev noj zuam thiab kis kab mob. Kev siv cov tshuaj tiv thaiv kab mob no rau hauv cov tshuaj tiv thaiv rau cov tsiaj nyeg thiab tsiaj qus, cia tib neeg nyob ib leeg, tseem muaj kev sib tw.

Tus sau kev koom tes:

MNA, MAJ, thiab MK tsim cov qauv ntawm tsab xov xwm. Txhua tus kws sau ntawv tau ua cov ntaub ntawv tshawb fawb thiab sau ib feem ntawm cov ntawv sau / sau cov ntaub ntawv. MNA thiab IM tsim thiab kho cov duab. ID thiab MK tau kho qhov tseem ceeb thiab ua pov thawj cov ntawv sau. Txhua tus kws sau ntawv tau nyeem thiab pom zoo rau cov ntawv luam tawm ntawm cov ntawv sau.

Nyiaj txiag:

MK tau txais nyiaj pab los ntawm Grant Agency of the Czech Republic (grant {{0}}}S) thiab ERD Funds, project CePaVip OPVVV (no. 384 CZ.02.1.01 /0.0/0.0/16_019/0000759). Cov peev nyiaj tsis muaj lub luag haujlwm hauv kev tsim cov kev tshawb fawb, kev sau cov ntaub ntawv, thiab kev tshuaj xyuas, kev txiav txim siab tshaj tawm, lossis kev npaj cov ntawv sau.

Institutional Review Board Statement: Tsis siv tau.

Cov Lus Qhia Txog Kev Pom Zoo: Tsis siv tau.

Cov Lus Qhia Muaj Cov Ntaub Ntawv: Tsis siv tau

Kev tsis sib haum xeeb ntawm kev txaus siab: Cov kws sau ntawv tshaj tawm tias qhov kev tshawb fawb tau ua thaum tsis muaj kev lag luam lossis kev sib raug zoo nyiaj txiag uas tuaj yeem txhais tau tias muaj kev tsis sib haum xeeb ntawm kev txaus siab.

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