Ib Heterologous AZD1222 Priming Thiab BNT162b2 Boosting Regimen Ntau Elicits Neutralizing Antibodies, Tab sis Tsis Nco T Cells, dua li Homologous BNT162b2 Regimen
Aug 07, 2023
abstract
Keeb Kwm: Kev sib piv kev tshuaj xyuas ntawm SARS-CoV-2- cov lus teb tshwj xeeb tiv thaiv kab mob tau txais los ntawm ntau hom kev txhawb nqa tseem ceeb yuav tsum tsim kom muaj kev tswj hwm zoo rau kev tswj hwm ntawm COVID-19. Txoj kev: Hauv qhov kev soj ntsuam kev soj ntsuam yav tom ntej no, kev soj ntsuam tshwj xeeb ntawm immunoglobulin G (IgG) thiab cov tshuaj tiv thaiv tsis zoo (nAbs) nrog rau cov lus teb tshwj xeeb T-cell hauv cov hnub nyoog sib xws ntawm homologous BNT162b2 / BNT162b2 los yog AZD122222 / AZD1222A / Kev txhaj tshuaj BNT162b2, thiab ua ntej hom tsiaj qus SARS-CoV{19}} kev kis kab mob / tshuaj tiv thaiv tau raug soj ntsuam. Cov txiaj ntsig: Cov tshuaj tiv thaiv kab mob siab tshaj plaws tau ua tiav tom qab txhaj tshuaj tiv thaiv thib ob hauv pawg tshuaj tiv thaiv tsis zoo thiab tom qab thawj koob tshuaj hauv pawg ua ntej kis kab mob / tshuaj tiv thaiv. Peak titers ntawm anti-spike IgG thiab nAb tau nce siab dua hauv AZD1222 / BNT162b2 txhaj tshuaj tiv thaiv thiab ua ntej kis kab mob / pab pawg tshuaj tiv thaiv dua li hauv BNT162b2 / BNT162b2 lossis AZD1222 / AZD1222 pawg. Txawm li cas los xij, qhov zaus ntawm interferon-c-tsim CD4 ntxiv rau T hlwb tau siab tshaj plaws hauv pawg tshuaj tiv thaiv BNT162b2 / BNT162b2. Cov txiaj ntsig zoo sib xws tau pom hauv kev tsom xam ntawm polyfunctional T cells. Thaum nAb thiab CD4 ntxiv rau T-cell cov lus teb tawm tsam Delta variant tau txheeb xyuas, pawg neeg kis kab mob ua ntej / tshuaj tiv thaiv tau pom cov lus teb ntau dua li cov pab pawg ntawm lwm cov tshuaj tiv thaiv homologous lossis heterologous. Cov ntsiab lus: nAbs tau txais txiaj ntsig zoo los ntawm kev txhaj tshuaj heterologous AZD1222 / BNT162b2, nrog rau kev kis kab mob ua ntej / txhaj tshuaj tiv thaiv, qhov tshwj xeeb CD4 ntxiv rau T-cell cov lus teb tau zoo los ntawm kev txhaj tshuaj homologous BNT162b2. Variant-paub txog kev tiv thaiv kab mob yog qhov ua tau zoo dua los ntawm kev kis kab mob ua ntej / - txhaj tshuaj tiv thaiv ntau dua li lwm cov tshuaj tiv thaiv homologous lossis heterologous.
cistanche tubulosa- txhim kho lub cev tiv thaiv kab mob
1. Taw qhia
Mob hnyav ua pa nyuaj rau tus mob coronavirus 2 (SARS-CoV-2) tau kis thoob ntiaj teb txij li thaum nws tshwm sim thaum lub Kaum Ob Hlis 2019, thiab kev tsim cov tshuaj tiv thaiv zoo tiv thaiv kab mob coronavirus 2019 (COVID-19) tau nrawm dua [1 ]. Qhov kev ua tiav ntawm qhov kev sim siab tau pom sai sai, thiab ntau cov tshuaj tiv thaiv uas siv cov kab mob sib kis (S) protein ua cov tshuaj tiv thaiv antigen tau ua tiav pom kev nyab xeeb thiab ua haujlwm tau zoo hauv kev tiv thaiv cov tsos mob COVID-19. Tshwj xeeb, mRNA-based tshuaj tiv thaiv BNT162b2 (Comirnaty, Pfifizer-BioNTech) thiab adenovirus vector-based vaccine AZD1222 (Vaxzevria, AstraZeneca) tau pib pom zoo thiab dav siv raws li ob-dose prime-boost regimen. Ob koob tshuaj BNT162b2 muaj 95 feem pua (95 feem pua ntawm kev ntseeg siab [CI], 90– 98 feem pua ) kev ua tau zoo tiv thaiv cov tsos mob COVID-19 [2], thiab ob koob tshuaj AZD1222 muaj 70 feem pua (95 feem pua CI, 55–81 feem pua ) kev ua tau zoo [3]. Intriguingly, heterologous prime-boost regimens ntawm daim ntawv tso cai COVID{31}} cov tshuaj tiv thaiv tau txais kev txaus siab heev thiab tau pib tom qab hauv ntau lub teb chaws txawm hais tias tsis muaj cov ntaub ntawv hais txog kev tiv thaiv kab mob thiab kev nyab xeeb. BNT162b2 muab raws li kev txhawb nqa rau cov tib neeg thawj zaug txhaj tshuaj tiv thaiv nrog AZD1222 induced robust S-specific immunoglobulin G (IgG) antibody (Ab) titers, neutralizing antibody (nAb) cov lus teb, thiab interferon-c ntxiv (IFN-c ntxiv) T hlwb ,5] ib. Txawm li cas los xij, ob peb txoj kev tshawb fawb tau soj ntsuam qhov ua tau zoo ntawm heterologous AZD1222 / BNT162b2 txhaj tshuaj tiv thaiv piv rau homologous BNT162b2 / BNT162b2 txhaj tshuaj [6-8], thiab cov kev tshawb fawb no tsis muaj kev ntsuam xyuas ntawm S-specific T-cell teb. Yog li ntawd, txawm tias kev txhaj tshuaj tiv thaiv kab mob AZD1222/BNT162b2 ua rau muaj zog sib txawv nAb lossis T-cell cov lus teb tseem tsis meej. Lwm qhov piv txwv ntawm heterologous priming-boosting tuaj yeem pom hauv cov tib neeg uas tau kis tus kabmob SARS-CoV-2 thiab tom qab txhaj tshuaj tiv thaiv tus kabmob. Ntau qhov kev tshawb fawb tau pom tias qhov kev sib khi tshwj xeeb Ab thiab nAb tau kuaj pom nyob rau hauv cov neeg mob uas muaj kab mob ua ntej thiab txhaj tshuaj tiv thaiv, txawm hais tias tsis muaj kev tshuaj ntsuam sib piv [9,10]. Cov neeg ua haujlwm saib xyuas kev noj qab haus huv uas muaj tus kab mob SARS-CoV-2 ua ntej muaj tus kab mob Ab titers ntau dua los teb rau ib koob tshuaj tiv thaiv mRNA dua li cov uas tsis tau kis yav dhau los [11]. Tsis tas li ntawd, cov tib neeg uas muaj tus kab mob ua ntej muaj kev txhim kho S-tshwj xeeb T-cell cov lus teb thiab Ab-secreting nco Bcell cov lus teb tom qab koob tshuaj thawj zaug yam tsis muaj koob tshuaj ntxiv [12]. Hauv kev tshawb fawb tam sim no, peb tau tshuaj xyuas qhov kev lom zem thiab cellular immunogenicity ntawm homologous thiab heterologous prime-boost regimens nyob rau hauv ib tug yav tom ntej kev soj ntsuam cohort nrog ib sab sib piv ntawm S-specific binding Ab, nAb, thiab Sspecifific CD4 ntxiv rau T-cell teb. . Peb kuj tau soj ntsuam cov txiaj ntsig ntawm kev tiv thaiv kab mob hauv cov neeg koom nrog uas tau kis tus kab mob SARS-CoV-2 thiab tau txais cov tshuaj tiv thaiv COVID-19 los txiav txim seb puas muaj tus kab mob ua ntej thiab kev txhaj tshuaj tiv thaiv zoo tiv thaiv kab mob Delta variant.
cistanche cov txiaj ntsig rau txiv neej-ua kom muaj zog tiv thaiv kab mob
2. Cov txheej txheem
2.1. Kawm tsim qauv
Lub koom haum ntau lub zeem muag tau tsim nyob rau lub Peb Hlis 2021 los kawm txog kev tiv thaiv kab mob tiv thaiv kab mob tiv thaiv COVID-19. Cov koom nrog hauv pawg pab pawg no tau yeem xaiv los ntawm cov neeg ua haujlwm saib xyuas kev noj qab haus huv thiab thawj zaug tau teem sijhawm kom tau txais ob koob tshuaj BNT162b2 ntawm 3-lub lim tiam lossis AZD1222 ntawm 12- lub lim tiam. Txawm li cas los xij, ib feem ntawm cov tib neeg tau txhaj tshuaj tiv thaiv nrog AZD1222 tau txais koob tshuaj BNT162b2 thaum lub Tsib Hlis thiab Lub Rau Hli 2021 thiab tau suav nrog hauv pawg txhaj tshuaj AZD1222/BNT162b2. Ntawm cov neeg koom nrog hauv pawg, cov neeg uas tau kis tus kab mob SARSCoV{15}} ua ntej thiab tau txais BNT162b2 lossis AZD1222 tau suav nrog ua ntej kis kab mob / pab pawg tshuaj tiv thaiv. Txhua tus neeg tau txais tshuaj tiv thaiv tau txheeb xyuas hauv qhov kev tshawb fawb no tau muaj hnub nyoog sib npaug ntawm cov pab pawg. Cov ntshav peripheral tau sau los ntawm txhua tus neeg koom nrog hauv pawg ntawm txhua lub sijhawm (T): ua ntej thiab 3 lub lis piam tom qab txhaj tshuaj thib 1 (T1 thiab T2, raws li), 5 lub lis piam tom qab koob tshuaj BNT162b2, lossis 11 lub lis piam tom qab 1st. AZD1222 koob tshuaj (T3), thiab 14 lub lis piam tom qab txhaj tshuaj thib 1 (T4). Daim duab schematic ntawm txoj kev tshawb fawb raws tu qauv yog muab nyob rau hauv daim duab 1. Rau kev sib piv, cov qauv convalescent tau txais los ntawm cov neeg mob uas tsis tau txhaj tshuaj tiv thaiv kab mob SARSCoV-2 Delta variant tau lees paub los ntawm lub sijhawm tiag tiag rov qab hloov pauv polymerase saw cov tshuaj tiv thaiv siv Seegene Allplex { {38}}nCoV Assay kit (Seegene, Korea) and Illumina BTSeq SARS-CoV-2 whole-genome sequencing kit (Celemics Inc, Korea) on a MiSeq sequencer (150-bp paired-end mode; Illumina, San Diego, CA, USA). Lub hauv paus kab ke tau txais los ntawm BTseq tau muab piv rau NCBI siv ntu ntu NC_045512.2 siv IGV 2.10 software kom paub meej tias Delta variant. Txoj kev tshawb no tau pom zoo los ntawm lub koom haum saib xyuas pawg thawj coj ntawm txhua lub koom haum koom nrog thiab ua raws li cov hauv paus ntsiab lus ntawm Kev Tshaj Tawm ntawm Helsinki. Txhua tus neeg tuaj koom tau sau ntawv tso cai ua ntej tso npe.
2.2. Kawm cov neeg koom
Cov pab pawg no suav nrog 22 tus neeg koom nrog uas tau txhaj tshuaj tiv thaiv homologous BNT162b2 / BNT162b2 (lub hnub nyoog nruab nrab, 38.0 xyoo; 31.8 feem pua cov txiv neej), 20 tus neeg koom uas tau txhaj tshuaj tiv thaiv homologous AZD1222 / AZD1222 (txhais hnub nyoog, txiv neej; 323.7 feem pua) , thiab 9 tus neeg koom uas tau txais kev txhaj tshuaj tiv thaiv kab mob heterologous AZD1222 / BNT162b2 (lub hnub nyoog nruab nrab, 38.2 xyoo; 33.3 feem pua cov txiv neej). Ntawm 11 tus neeg koom nrog ua ntej-hom SARS-CoV{27}} kab mob (txhais hnub nyoog, 38.5 xyoo; 27.3 feem pua txiv neej), 2 thiab 9 tau txhaj tshuaj tiv thaiv BNT162b2/BNT162b2 thiab AZD1222/AZD1222, raws li. Cov pej xeem ntawm cov pab pawg sib txawv tau txhaj tshuaj muaj nyob rau hauv Daim Ntawv Ntxiv 2. Txhua tus neeg koom nrog cov kab mob qus SARS-CoV-2 yav dhau los tau ntsib tus mob asymptomatic lossis mob hnyav COVID-19, thiab 3 ntawm lawv muaj mob ntsws. Lub sijhawm nruab nrab ntawm kev lees paub ntawm COVID-19 mus rau thawj zaug txhaj tshuaj yog 121.5 (interquartile range [IQR], 102.3–252.5) hnub. Cov pej xeem ntawm cov neeg koom nrog yav dhau los hom tsiaj qus SARS-CoV-2 kab mob thiab tshuaj tiv thaiv yog muab nyob rau hauv Cov Lus Qhia Ntxiv 1. Cov qauv kuaj tau los ntawm 17 tus neeg mob (lub hnub nyoog nruab nrab, 53 xyoo; 52.9 feem pua cov txiv neej) kis tus kab mob SARS -CoV-2 Delta variant and hospitalized for moderate to critical COVID-19 (moderate, 17.6%); hnyav, 35.3%; mob hnyav, 47.1 feem pua ). Lub sijhawm nruab nrab ntawm qhov pib ntawm COVID-19-cov tsos mob ntsig txog kev kuaj yog 24 (IQR, 22–32) hnub. Cov pej xeem ntawm SARS-CoV-2 Cov neeg koom nrog Delta convalescent muaj nyob rau hauv Ntxiv Table 2 thiab Table 3.
2.3. Binding cov tshuaj tiv thaiv
SARS-CoV-2 S-specific binding Abs tau txheeb xyuas los ntawm kev lag luam immunoassay. Lub Eecsys anti-S protein assay (Roche Diagnostics, Lub teb chaws Yelemees) yog ib qho electrochemiluminescence immunoassay siv los kuaj SARS-CoV-2 S-specific antibodies ntawm Cobas e411 analyzer (Roche Diagnostics, Lub teb chaws Yelemees), nrog rau kev ntsuas ntau los ntawm { {8}}.4 U/mL txog 25{25}} U/mL (txog 2500 U/mL nrog onboard 1:10 dilution, thiab mus txog 12,500 U/mL nrog onboard 1:50 dilution). Lub recombinant receptor binding domain ntawm S protein tau siv nrog ob lub ntsiab lus antigen sandwich. Cov antigens hauv cov reagent capture feem ntau anti-SARSCoV-2 IgG. Eecsys anti-nucleocapsid protein assay (Roche Diagnostics, Lub teb chaws Yelemees) tau siv los kuaj xyuas cov kab mob SARS-CoV-2 yav dhau los, nrog rau kev txiav tawm ntawm 1.0.
cistanche ntxiv cov txiaj ntsig-nce kev tiv thaiv
2.4. Plaque-reduction neutralization assay
Plaque-reduction neutralization assays for wild-type SARS-CoV- 2 viruses (BetaCoV/Korea/KCDC03/2020) and the Delta variant strain YS117 (GenBank accession number MZ798798 and GISAID accession number EPI{ {8}}ISL_3411836) tau ua tiav siv cov qauv ntshav plasma. Tus kab mob no tau loj hlob ntawm Vero E6 hlwb hauv chav kuaj biosafety qib 3 ntawm Avison Biomedical Research Center hauv Seoul, Kauslim. Inactivated plasma samples (135 lL) ntawm inactivated plasma kuaj tau 2-fold serially diluted (1:40 txog 1:1280) thiab ntxiv rau qhov sib npaug ntawm 100 npaug ntawm 50 feem pua cov kab mob kab mob kis kab mob (TCID50) ntawm kab mob vais lav. Cov kev sib cais uas muaj 100 npaug ntawm TCID50 tau tsim nyob rau hauv 96- cov phiaj zoo rau 60 min ntawm 37 C. Cov kab mob-plasma sib xyaw tau tsim rau 60 min ntawm 37 C hauv qhov cub CO2. Tom qab ntawd cov kab mob-plasma sib xyaw tau muab ntxiv rau Vero E6 hlwb cov noob hauv ib lub 24-zoo phaj nrog 1x105 hlwb/zoo thiab incubated rau 1 h ntawm 37 C. Overlay media muaj li ntawm 2 feem pua fetal bovine serum (FBS) hauv DMEM thiab 1 feem pua agar tau ntxiv rau E6 hlwb thiab incubated rau 3 hnub nyob rau hauv 37 C nyob rau hauv ib tug CO2 incubator. Tom qab tsim cov quav hniav, 10 feem pua formaldehyde tov thiab 0.33 feem pua ntxhiab liab hauv phosphate-buffered saline (PBS) tau siv los kho thiab stain lub cell kab lis kev cai txheej. Neutralizing dilution ntawm txhua tus qauv tau txiav txim siab los ntawm kev txheeb xyuas lub qhov dej nrog qhov siab tshaj plaws ntawm cov ntshav plasma dilution yam tsis muaj kev saib xyuas cytopathic. Qhov 50 feem pua ntawm cov tshuaj tsis zoo (ND50) tau qhia tias yog qhov sib npaug ntawm cov ntshav plasma, uas ua rau 50 feem pua ntawm cov quav hniav txo qis piv rau cov kab mob zoo. Txoj kev Spearman-Kärber tau siv los xam ND50 titers. Los ntawm kev sib piv rau WHO thoob ntiaj teb tus qauv sera (NIBSC 20–136; nAb titer: 1000 IU/mL), nAb titers tau hloov mus rau thoob ntiaj teb units ib milliliter (IU/mL).
Fig. 1. Schematic sawv cev ntawm pawg neeg tau txais cov tshuaj tiv thaiv. Txoj kev tshawb fawb txog kev tshawb pom ntawm SARS-CoV-2 spike-specific binding antibodies, neutralizing antibodies, thiab T-cell teb nyob rau hauv peripheral cov ntshav kuaj los ntawm cov tib neeg txhaj tshuaj tiv thaiv COVID-19. Txoj kev tshawb no suav nrog BNT162b2/BNT162b2 (n=22), AZD1222/AZD1222 (n=20), AZD1222/BNT162b2 (n=9), thiab ua ntej wild-type SARS-CoV{{20 }} kab mob / tshuaj tiv thaiv (n=11) pawg. Ntawm qhov ua ntej-hom SARS-CoV{24}} kab mob / tshuaj tiv thaiv, 2 thiab 9 tau txhaj tshuaj tiv thaiv nrog BNT162b2/BNT162b2 thiab AZD1222/AZD1222, raws li. Keeb kwm ntawm SARS-CoV-2 kab mob tau lees paub los ntawm qhov zoo los tiv thaiv SARS-CoV-2 nucleocapsid antibody test. T, lub sijhawm taw tes; wb ,week.
2.5. Kev ntsuam xyuas T-cell
Peripheral ntshav mononuclear hlwb (PBMCs) raug cais los ntawm qhov ntom ntom gradient centrifugation siv cov hlab ntsha Leucosep (Greiner Bio-One) uas muaj cov lymphocyte sib cais nruab nrab. Tom qab centrifugation ntawm 800g rau 15 min nrog lub nres-tawm, lub enriched cell feem uas muaj PBMCs tau sau thiab ntxuav nrog 20 mL ntawm PBS. Tom qab centrifugation ntawm 300g rau 10 min, lub cell pellet tau resuspended hauv 10 mL ntawm PBS rau suav. Tom qab centrifugation ntawm 300g rau 10 min, cov hlwb tau khaws cia hauv FBS nrog 10 feem pua dimethyl sulfoxide ntawm 180 C kom txog thaum siv. Rau intracellular cytokine staining (ICS) ntawm IFN-c, interleukin-2 (IL-2), thiab qog necrosis factor (TNF), peb siv peptide pas dej ua ke ntawm 15-mer peptides overlapping los ntawm 11 amino acids npog cov immunodominant qhov chaw ntawm SARS-CoV-2 Wuhan S protein (aa 304–338, 421–475, 492–519, 683–707, 741–770, 785–802, and 885–1273; Biotec). Txhawm rau sib piv T-cell cov lus teb tawm tsam Wuhan thiab Delta strains, peb siv ob qhov sib txawv ntawm S peptide pas dej ua ke suav nrog thaj chaw uas tsis tau khaws cia ntawm S ib ntu ntawm Wuhan thiab Delta (B.1.617.2 kab) hom (Miltenyi Biotec). Tom qab thawing PBMCs thiab so lawv ib hmos, 1 106 PBMCs tau txhawb nqa nrog cov pas dej peptide ntawm qhov kawg ntawm 1 mg / mL thiab tshuaj tiv thaiv tib neeg CD28 / CD49d (1 mg / mL; BD Biosciences) rau 1 h hauv { {45}}zoo phaj hauv RPMI-1640 xov xwm uas muaj 1 feem pua penicillin-streptomycin, 2 mM L-glutamine, thiab 10 feem pua FBS. PBMC kab lis kev cai tau incubated rau lwm 5 teev tom qab sib ntxiv ntawm brefeldin A thiab monensin (BD Biosciences) ntawm 37 C hauv 5 feem pua CO2. Tom qab qhov stimulation, hlwb raug ntxuav nrog PBS thiab stained nrog Live/Dead-Aqua (Invitrogen) rau 20 min nyob rau hauv chav tsev kub, ua raws li ib tug cocktail ntawm nto Abs rau 20 min nyob rau hauv chav tsev kub, nrog rau anti-CD14- BV510, anti-CD19-BV510, anti-CD4- BV650, anti-CD3-BV786, thiab anti-CD8-APC-Cy7 (BD Bioscience). Cells tau kho thiab permeabilized siv Foxp3/Transcription Factor Staining Buffer Set (eBioscience) thiab tom qab ntawd stained nrog ib qho dej cawv ntawm intracellular Abs, suav nrog anti-TNF-FITC, anti-IL-2-PE (eBioscience), thiab tiv thaiv- IFN-c-APC (BD Biosciences) rau 20 min ntawm chav tsev kub. Tom qab ua tiav cov staining, cov hlwb raug tshuaj xyuas ntawm LSR II ntsuas nrog FACSDiva (BD Biosciences), thiab cov ntaub ntawv tau txheeb xyuas hauv FlowJo software (FlowJo LLC).
cistanche cog-nce kev tiv thaiv kab mob
2.6. Kev txheeb cais
Cov ntaub ntawv plotted nyob rau hauv linear scale tau qhia raws li lub ntsiab lus ± tus qauv sib txawv. Cov ntaub ntawv teev nyob rau hauv logarithmic nplai tau qhia raws li geometric txhais tau tias ± geometric qauv sib txawv. Mann–Whitney U lossis Wilcoxon kev xeem tau thov rau kev sib piv tsis sib xws lossis sib piv, feem. Kev txheeb xyuas txheeb cais tau {{0}}tailed, nrog P < 0.05 suav tias yog qhov tseem ceeb. Txhua qhov kev ntsuam xyuas tau ua tiav hauv R studio lossis GraphPad Prism v9.0.
3. Cov txiaj ntsig
3.1. Kinetics ntawm kev tiv thaiv kab mob elicited los ntawm ntau yam tshuaj tiv thaiv kab mob
Ua ntej, peb tau tshuaj xyuas cov tshuaj tiv thaiv S IgG titers tom qab txhaj tshuaj tiv thaiv kab mob sib txawv. Raws li qhov xav tau, thawj koob tshuaj tau nce ntau ntxiv los tiv thaiv S IgG titers (T2), thiab qhov koob thib ob tau nce ntxiv los tiv thaiv S IgG titers hauv homologous BNT162b2 / BNT162b2 (T3) thiab AZD1222 / AZD1222 txhaj tshuaj tiv thaiv (T4) thiab heterologous. Kev txhaj tshuaj BNT162b2 (T4) pawg (Fig. 2A). Hauv pab pawg neeg kis kab mob ua ntej / txhaj tshuaj tiv thaiv, thawj koob tshuaj ntau tshaj plaws tau nce los tiv thaiv S IgG titers (T3), tab sis koob thib ob tsis tau nce ntxiv los tiv thaiv S IgG titers (T4). Peb kuj tau tshuaj xyuas S-specific CD4 ntxiv rau T-cell cov lus teb tom qab kev txhawb nqa ncaj qha ex vivo nrog cov pas dej peptide npog cov SARSCoV-2 Wuhan wild-type S protein sequence. Raws li ICS, thawj koob tshuaj tau nce qhov zaus ntawm IFN-c-tsim hlwb ntawm CD4 ntxiv rau T hlwb, thiab qhov koob thib ob tau nce qhov zaus hauv BNT162b2 / BNT162b2 (T3) thiab AZD1222 / BNT162b2 txhaj tshuaj tiv thaiv (T4) pawg. (Fig. 2B). Hauv AZD1222 / AZD1222 thiab pab pawg kis kab mob ua ntej / txhaj tshuaj tiv thaiv, thawj koob tshuaj tau nce ntau zaus ntawm IFN-c ntxiv cov hlwb ntawm CD4 ntxiv rau T hlwb, tab sis koob thib ob tsis ntxiv qhov zaus.
3.2. Kev sib piv ntawm Ab titers ntawm cov kev tswj sib txawv
Tom ntej no, peb muab piv rau lub ncov titers ntawm kev khi Ab ntawm cov tshuaj tiv thaiv sib txawv. Raws li lub ncov titers, peb xaiv cov tshuaj tiv thaiv S IgG titers tom qab koob thib ob hauv BNT162b2 / BNT162b2, AZD1222 / AZD1222, thiab AZD1222 / BNT162b2 txhaj tshuaj tiv thaiv kab mob thiab tom qab thawj koob tshuaj hauv pawg ua ntej kis kab mob / tshuaj tiv thaiv. Peak titers ntawm anti-S IgG tau ntau dua nyob rau hauv pawg tshuaj tiv thaiv AZD1222/BNT162b2 dua li hauv BNT162b2/BNT162b2 lossis AZD1222/ AZD1222 tshuaj tiv thaiv pawg (Fig. 3A). Ib yam li ntawd, lub ncov titers ntawm anti-S IgG tau nce siab dua nyob rau hauv cov kab mob ua ntej / tshuaj tiv thaiv ntau dua li hauv pawg tshuaj tiv thaiv BNT162b2 / BNT162b2 lossis AZD1222 / AZD1222. Tsis muaj qhov sib txawv ntawm cov tshuaj tiv thaiv S IgG titers ntawm AZD1222 / BNT162b2 thiab cov kab mob ua ntej / - pab pawg txhaj tshuaj. Peb kuj tau soj ntsuam nAb titers ntawm cov ntsiab lus siab tshaj plaws: tom qab koob thib ob hauv BNT162b2 / BNT162b2, AZD1222 / AZD1222, thiab AZD1222 / BNT162b2 pawg tshuaj tiv thaiv thiab tom qab thawj koob tshuaj hauv pawg neeg ua ntej kis kab mob / tshuaj tiv thaiv. Remarkably, nAb titers tau ntau dua nyob rau hauv pawg tshuaj tiv thaiv AZD1222/BNT162b2 dua li hauv pawg tshuaj tiv thaiv BNT162b2/BNT162b2 lossis AZD1222/AZD1222 (Fig. 3B). Tsis tas li ntawd, nAb titers tau nce siab dua nyob rau hauv pawg ua ntej kis kab mob / tshuaj tiv thaiv ntau dua li hauv pawg tshuaj tiv thaiv BNT162b2 / BNT162b2 lossis AZD1222 / AZD1222. Tsis muaj qhov sib txawv ntawm nAb titers ntawm AZD1222 / BNT162b2 thiab pab pawg kis kab mob / txhaj tshuaj tiv thaiv ua ntej. Qib ntawm cov lus teb lom zem uas tau hais los ntawm ntau hom kev txhaj tshuaj tiv thaiv kab mob tau muab faib ua cov neeg muaj zog, nruab nrab, thiab tsis muaj / tsis muaj zog teb raws li qhov feem pua ntawm qeb duas. Qhov feem pua ntawm cov neeg teb muaj zog tau siab tshaj plaws hauv pawg neeg kis kab mob ua ntej / txhaj tshuaj tiv thaiv, ua raws li pawg tshuaj tiv thaiv AZD1222/BNT162b2 txog kev tshuaj ntsuam xyuas ntawm anti-S IgG (Fig. 3C) thiab nAb (Fig. 3D). Muab ua ke, cov txiaj ntsig no qhia tau hais tias heterologous priming thiab boosting, nrog rau ob qho tib si AZD1222 / BNT162b2 txhaj tshuaj tiv thaiv thiab kev kis tus kab mob ua ntej / txhaj tshuaj tiv thaiv, muaj txiaj ntsig zoo hauv kev tsim cov lus teb zoo tshaj li homologous priming thiab boosting.
3.3. Kev sib piv ntawm S-specific CD4 ntxiv rau T-cell cov lus teb ntawm cov kev tswj sib txawv
Peb kuj tau muab piv rau S-tshwj xeeb CD4 ntxiv rau T-cell cov lus teb ntawm cov tshuaj tiv thaiv sib txawv ntawm cov ntsiab lus ntawm lub sijhawm ncov: tom qab koob thib ob hauv BNT162b2 / BNT162b2, AZD1222 / AZD1222, thiab AZD1222 / BNT162b2 cov tshuaj tiv thaiv ua ntej thiab tom qab thawj koob tshuaj tiv thaiv kab mob. pab pawg kab mob / txhaj tshuaj tiv thaiv. Tsis zoo li cov tshuaj tiv thaiv-S IgG thiab nAb titers, qhov zaus ntawm IFN-c ntxiv cov hlwb ntawm CD4 ntxiv rau T hlwb yog siab tshaj hauv pawg tshuaj tiv thaiv BNT162b2/BNT162b2 (Fig. 4A). Qhov feem pua ntawm cov neeg teb muaj zog kuj tseem siab tshaj plaws hauv pawg tshuaj tiv thaiv BNT162b2 / BNT162b2, tom qab los ntawm pawg neeg kis kab mob / tshuaj tiv thaiv ua ntej (Fig. 4B). Cov txiaj ntsig no qhia tau tias kev txhaj tshuaj nrog qhov thib ob homologous boost ntawm BNT162b2 ua tau zoo dua elicits nco T-cell cov lus teb ntau dua li qhov thib ob heterologous boost txhaj tshuaj lossis thawj koob tshuaj tiv thaiv tom qab SARS-CoV{29}} kab mob. Ntawm qhov tsis sib xws, heterologous prime-boost regimens muaj feem ntau yuav txhim kho qib siab ntawm kev tiv thaiv kab mob humoral. Peb kuj tau txheeb xyuas cov txheeb ze zaus ntawm polyfunctional CD4 ntxiv rau T hlwb uas ib txhij tsim ntau cytokines (ie, IFN-c, IL-2, thiab/los yog TNF). Pawg tshuaj tiv thaiv BNT162b2 / BNT162b2 tau nthuav tawm ntau zaus ntau dua ntawm cov hlwb ua haujlwm ua 2 cytokines ntawm S-specific CD4 ntxiv rau T hlwb dua li AZD1222 / AZD1222 lossis AZD1222 / BNT162bC2. Tsis muaj qhov sib txawv ntawm qhov zaus ntawm BNT162b2 / BNT162b2 txhaj tshuaj tiv thaiv thiab pab pawg kis kab mob ua ntej. Qhov zaus ntawm cov hlwb polyfunctional tau nce siab dua hauv pawg tshuaj tiv thaiv AZD1222/BNT162b2 dua li hauv pawg tshuaj tiv thaiv AZD1222/AZD1222. Pie graphs sawv cev rau ib leeg-, ob npaug-, thiab triple-zoo CD4 ntxiv rau T hlwb nyob rau hauv cov nqe lus ntawm cytokine ntau lawm teb rau S overlapping peptide pas dej ua ke kuj qhia tau hais tias muaj ntau zaus ntawm ob-lossis triple-zoo hlwb hauv BNT162b2 / BNT162b2 txhaj tshuaj tiv thaiv thiab ua ntej. kab mob/- pab pawg txhaj tshuaj (Fig. 4D).
3.4. Lub cev tiv thaiv kab mob tawm tsam Delta variant ntawm ntau yam kev tswj hwm
Thaum kawg, peb txheeb xyuas cov lus teb tiv thaiv kab mob rau Delta variant. Hauv qhov kev tshuaj ntsuam no, peb suav nrog cov neeg uas tsis muaj hnub nyoog uas rov zoo los ntawm SARS-CoV-2 Delta tus kab mob rau kev sib piv. Delta variant-specific nAb titers tau ntau dua nyob rau hauv pawg neeg kis kab mob ua ntej / txhaj tshuaj tiv thaiv ntau dua li hauv BNT162b2 / BNT162b2, AZD1222 / AZD1222, lossis AZD1222 / BNT162b2 txhaj tshuaj tiv thaiv kab mob, thiab txawm tias siab dua li cov neeg nyob hauv Delta configurations. . Peb kuj tau tshuaj xyuas CD4 ntxiv rau T-cell teb tawm tsam S protein ntawm Delta variant. Hauv qhov kev tshuaj ntsuam no, peb tau ua ICS ntawm IFN-c tom qab ncaj qha ex vivo stimulation siv ob qhov sib txawv ntawm S peptide pas dej ua ke suav nrog thaj chaw uas tsis muaj kev tiv thaiv ntawm S sib lawv liag ntawm Wuhan thiab Delta strains thiab suav qhov piv ntawm qhov zaus ntawm Delta Sspecifific IFN-c ntxiv. cell mus rau qhov zaus ntawm Wuhan S-specific IFN-c ntxiv rau cov hlwb. Raws li qhov xav tau, qhov sib piv tau siab tshaj plaws hauv Delta convalescent cov neeg. Intriguingly, qhov sib piv tau siab dua nyob rau hauv pawg neeg kis kab mob ua ntej / txhaj tshuaj ntau dua li hauv pawg tshuaj tiv thaiv BNT162b2 / BNT162b2 (Daim duab 5B), txawm hais tias Wuhan S-specific CD4 ntxiv rau T-cell cov lus teb tau siab tshaj hauv BNT162b2 / BNT162b2 tshuaj tiv thaiv pawg (Fig. 4A). Muab ua ke, cov txiaj ntsig no qhia tau hais tias nAb thiab CD4 ntxiv rau T-cell cov lus teb uas hla-pom qhov sib txawv ntawm Delta yog qhov ua tau zoo dua los ntawm kev kis kab mob ua ntej / txhaj tshuaj ntau dua li homologous lossis heterologous tshuaj tiv thaiv kab mob.
Fig. 2. Antibody thiab T-cell teb elicited los ntawm ntau yam prime-boost regimens. Cov tshuaj tiv thaiv kab mob ntev ntev raws li lub sijhawm ua piv txwv los ntawm kev txhaj tshuaj tiv thaiv ua ntej mus rau 14 lub lis piam tom qab txhaj tshuaj thawj zaug. (A) SARS-CoV-2 spike-specific binding antibodies were measured in BNT162b2/BNT162b2 (n=22), AZD1222/AZD1222 (n=20), AZD1222/ BNT162b2 (n {{ 20}}), thiab ua ntej kis kab mob / txhaj tshuaj tiv thaiv (n=6) pawg. (B) SARS-CoV-2 spike-specifific CD4 plus T-cell responses were measured in BNT162b2/BNT162b2 (n=19), AZD1222/AZD1222 (n=18), AZD1222/BNT162b2 (n=9), thiab ua ntej kis kab mob / txhaj tshuaj tiv thaiv (n=7) pawg. Cov ntaub ntawv tau nthuav tawm raws li geometric txhais tau tias ± geometric SD (A) lossis txhais tau tias ± SD (B). Kev txheeb xyuas txheeb cais ntawm lub sijhawm cov ntsiab lus hauv txhua pab pawg tau ua tiav siv Wilcoxon kos npe-qib xeem. ns, tsis tseem ceeb; *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.
Fig. 3. Cov tshuaj tiv thaiv kab mob humoral thaum lub sij hawm siab tshaj. (A) SARS-CoV-2 spike-specific binding antibodies were connected among BNT162b2/BNT162b2 (n=22), AZD1222/ AZD1222 (n=20), AZD1222/BNT162b2 (n {{ 15}}), thiab ua ntej kis kab mob / txhaj tshuaj tiv thaiv (n=6) pawg ntawm cov ntsiab lus siab tshaj lub sijhawm. (B) Neutralizing antibodies tau muab piv nrog BNT162b2/BNT162b2 (n=22), AZD1222/AZD1222 (n=20), AZD1222/BNT162b2 (n=9), thiab ua ntej kis kab mob / txhaj tshuaj tiv thaiv ( n=11) pawg ntawm cov ntsiab lus siab tshaj lub sijhawm. Cov ntsiab lus ntawm lub sijhawm siab tshaj plaws tau raug xaiv raws li hauv qab no: tom qab koob thib ob hauv BNT162b2 / BNT162b2, AZD1222 / AZD1222, thiab AZD1222 / BNT162b2 pawg txhaj tshuaj thiab tom qab thawj koob tshuaj hauv pawg neeg ua ntej kis kab mob / txhaj tshuaj. Cov ntaub ntawv raug nthuav tawm raws li qhov ntsuas geometric ± geometric SD thiab txheeb xyuas qhov tseem ceeb siv Mann-Whitney xeem. (C thiab D) Cov feem pua ntawm cov neeg koom nrog ntau theem ntawm kev tiv thaiv kab mob humoral. Kev suav ntawm hom neeg teb (muaj zog, nruab nrab, thiab tsis muaj / tsis muaj zog) yog qhia raws li ib feem ntawm tus naj npawb ntawm cov neeg tau txais tshuaj tiv thaiv hauv txhua pab pawg. Hom neeg teb tau txiav txim los ntawm tus qhab nia feem pua suav los ntawm txhua tus neeg koom nrog txhaj tshuaj. ns, tsis tseem ceeb; *P < {{40}}.
4. Kev sib tham
Cov tshuaj tiv thaiv mRNA tau tso cai tam sim no thiab cov tshuaj tiv thaiv kab mob adenovirus vector tau pom tias muaj txiaj ntsig zoo hauv kev tiv thaiv COVID-19. Txawm li cas los xij, heterologous prime-boost txhaj tshuaj tiv thaiv tau raug txiav txim siab los txhim kho kev tiv thaiv kab mob thiab txo cov khoom tsis txaus [13]. Tsis tas li ntawd, cov teeb meem kev nyab xeeb tau raug tsa nrog cov tshuaj tiv thaiv kab mob adenovirus vector tom qab kev lees paub ntawm cov xwm txheej tsis zoo, suav nrog kev ua rau lub neej muaj kev phom sij cuam tshuam nrog kev txhaj tshuaj AZD1222, tshwj xeeb tshaj yog rau cov poj niam hluas [14,15]. Cov no tau coj mus rau heterologous mRNA booster txhaj tshuaj rau cov neeg uas twb tau txais thawj koob tshuaj AZD1222. Txawm hais tias tsis muaj cov ntaub ntawv ua tau zoo, ntau lub koom haum saib xyuas kev noj qab haus huv hauv tebchaws tau txais kev tswj hwm kev cai lij choj ntawm cov tshuaj tiv thaiv COVID-19. Yog li, kev sib piv kev kawm txog kev lom zem thiab kev tiv thaiv kab mob ntawm tes los ntawm ntau hom kev txhaj tshuaj tiv thaiv kab mob tseem ceeb yog cov ntaub ntawv thiab pab kom nkag siab zoo txog cov teeb meem hauv ntiaj teb. Nyob rau hauv txoj kev tshawb no, peb tau pom qhov sib txawv induction ntawm humoral thiab cellular tiv thaiv kab mob los ntawm heterologous prime-boost txhaj tshuaj tiv thaiv (Table 4 ntxiv). Nyob rau hauv qhov tsis sib xws rau ob theem tshwj xeeb khi Ab thiab nruab nrab titers, uas siab tshaj plaws hauv pawg tshuaj tiv thaiv AZD1222 / BNT162b2, S-specific CD4 ntxiv rau T-cell cov lus teb tau siab tshaj plaws hauv BNT162b2 / BNT162b2 tshuaj tiv thaiv pawg, tsis yog nyob rau hauv pawg tshuaj tiv thaiv kab mob AZD2222NT2 / AZB1. pab pawg. Cov qib qis ntawm S-specific CD4 ntxiv rau T cell cov lus teb hauv AZD1222/BNT162b2- cov neeg koom nrog txhaj tshuaj tiv thaiv tsis tau xav txog thiab tseem tuaj yeem ua rau cov tib neeg no muaj kev pheej hmoo kis mob SARS-CoV-2 hnyav. Peb qhov kev tshawb pom txawv ntawm cov uas tau tshaj tawm los ntawm Schmidt thiab cov npoj yaig, uas tau tawm tswv yim tias, raws li kev txhawb nqa ntawm BNT162b2, nAb titers thiab T-cell cov lus teb tau nce ntau hauv AZD1222- cov neeg tseem ceeb [7]. Txawm li cas los xij, qhov tseeb ntawm CD69 ntxiv rau IFN-c ntxiv cov hlwb ntawm CD4 ntxiv rau T hlwb tsuas yog nce ntxiv, thiab qhov kev tshawb fawb no tau txwv tsis pub qhov tob ntawm kev ua haujlwm ntawm S-specific T-cell cov lus teb. Rau cov tib neeg uas tau kis tus kab mob yav dhau los, thawj koob tshuaj tiv thaiv tuaj yeem ua raws li kev txhaj tshuaj tiv thaiv kab mob thiab muaj zog ua rau muaj kev lom zem thiab cov lus teb ntawm tes [16,17]. Raws li nAb titer tau suav tias yog qhov tseem ceeb ntawm kev tiv thaiv kev tiv thaiv kab mob SARS-CoV-2 [18], peb cov txiaj ntsig tau zoo nrog qhov kev tshawb pom tsis ntev los no ntawm kev muaj txiaj ntsig zoo rau kev tiv thaiv kab mob kis tau, nrog kev kho tshuaj tiv thaiv zoo ntawm > 90 feem pua tom qab thawj koob tshuaj rau cov neeg tau txais tshuaj tiv thaiv uas tau kis tus kab mob SARS-CoV-2 yav dhau los [19]. Tsis tas li ntawd, txawm tias muaj kev khiav tawm ntau ntawm nAb cov lus teb tawm tsam Delta sib txawv ntawm cov neeg koom nrog kev kawm, peb tau pom cov qib siab tshaj plaws ntawm nAb hla kev lees paub qhov sib txawv ntawm Delta hauv pab pawg neeg koom nrog cov tsiaj qus ua ntej SARS-CoV-2 kab mob thiab txhaj tshuaj tiv thaiv. Txawm li cas los xij, nyob rau hauv txoj kab nrog pawg tshuaj tiv thaiv heterologous AZD1222 / BNT162b2, cov neeg uas muaj kab mob ua ntej uas tau txhaj tshuaj muaj qhov tsis muaj zog S-specific CD4 ntxiv rau T-cell teb dua li cov tib neeg uas muaj homologous BNT162b2 / BNT162b2 txhaj tshuaj tiv thaiv yam tsis muaj kab mob ua ntej. Qhov tseem ceeb, peb cov txiaj ntsig tau pom tias ob koob tshuaj BNT162b2 ua rau muaj kev ntseeg siab thiab muaj zog induction ntawm S-specific CD4 ntxiv rau T-cell cov lus teb, ntau dua li lwm cov tshuaj tiv thaiv thawj zaug. Cov kev tshawb pom no zoo ib yam nrog rau daim ntawv tshaj tawm tsis ntev los no ntawm plaub qhov sib txawv ntawm COVID-19 tshuaj tiv thaiv [20], thaum peb qhov kev tshuaj ntsuam suav nrog cov txheej txheem kev txhawb nqa tseem ceeb tshaj plaws thiab kev tiv thaiv kab mob sib kis los ntawm kev kis kab mob ua ntej thiab txhaj tshuaj tiv thaiv. Raws li, mRNA tshuaj tiv thaiv platforms yuav raug xaiv rau lawv lub peev xwm los txhawb lub cim xeeb CD4 ntxiv rau T cell teb.Raws li qhov tshwm sim ntawm kev kis tus kab mob tom qab txhaj tshuaj tiv thaiv tau nce thoob ntiaj teb, muaj kev txaus siab rau kev tiv thaiv kev tiv thaiv los ntawm COVID-19. Raws li tus tshiab SARS-CoV-2 variants txuas ntxiv tshwm sim thiab evade humoral immune defenses, cellular tiv thaiv kab mob, uas lub hom phiaj dav dav ntawm SARS-CoV-2 epitopes lees paub los ntawm T cells, tuaj yeem muab kev tiv thaiv ruaj khov [21 ], txawm hais tias qhov kev txiav txim ntawm cov lus teb ntawm tes hauv cov tshuaj tiv thaiv kab mob sib kis tseem tsis tau txhais meej meej. Yog li ntawd, txawm tias qhov nce humoral immunogenicity ntawm heterologous AZD1222 / BNT162b2 txhaj tshuaj tiv thaiv tsis tu ncua txhais mus rau kev tiv thaiv kev txhim kho tseem tsis paub meej, thiab qhov no yuav tsum tau kawm ntxiv. Tsis tas li ntawd, txawm tias cov neeg uas tau tsim cov lus teb tsis zoo Tcell tom qab txhaj tshuaj, xws li cov tshuaj tiv thaiv nrog AZD1222, yuav tau txais txiaj ntsig los ntawm T-cell cov tshuaj tiv thaiv yuav tsum tau tshawb xyuas [22]. Ob qho tib si kis tau tus kab mob thiab tshuaj tiv thaiv kab mob tiv thaiv kab mob ib txwm ua tsis tau raws sijhawm; Txawm li cas los xij, kev tiv thaiv ntau dua zoo li tau muab rau cov neeg uas yav dhau los tau kis tus kab mob SARS-CoV-2 [23]. Hauv cov neeg tau txhaj tshuaj, kev sib kis nrog Omicron variant induces me nAb cov lus teb dua li kev kis tus kab mob Delta variant [24], thiab kuj tsis tshua paub txog qhov tshwm sim ntawm kev tiv thaiv hybrid uas tau muab los ntawm kev kis kab mob thiab tshuaj tiv thaiv nrog ntau hom. Txawm li cas los xij, muaj cov polyfunctional S-specific T hlwb nyob rau hauv yav dhau los muaj tus kab mob thiab txhaj tshuaj tiv thaiv cov neeg koom nrog hauv peb txoj kev tshawb fawb yog ua raws li kev txo qis hauv kev tiv thaiv tus kab mob COVID-19 hauv cov pej xeem no thiab tej zaum yuav ua rau muaj kev hloov kho kab mob hnyav tom qab rov ua dua nrog SARS. -CoV{100}} variants [25,26]. Txoj kev tshawb fawb tam sim no muaj ntau yam kev txwv. Ua ntej, cov qauv me me hauv pawg ua kom muaj kev txheeb xyuas cov ntaub ntawv nyuaj nyuaj; Yog li ntawd, peb cov kev tshawb pom yuav tsum tau ua pov thawj ntxiv hauv cov pab pawg loj dua. Qhov thib ob, peb tsis tuaj yeem kuaj cov qauv tom qab cov ntsiab lus los txiav txim siab txog kev ua haujlwm ntev thiab poob qis ntawm kev humoral thiab cellular tiv thaiv kab mob. Thib peb, peb cov txiaj ntsig tuaj yeem kwv yees qhov cuam tshuam ntawm subdominant T-cell epitopes sab nraum cov epitopes tseem ceeb. Thib plaub, peb tsuas yog kawm txog cov lymphocytes circulating lymphocytes, thiab yav tom ntej kev tshawb fawb ntawm cov qog ntshav qog ntshav tom qab txhaj tshuaj tiv thaiv yuav tsum nkag siab txog cov txheej txheem hauv qab ntawm cov lus teb sib txawv tau pom ntawm no. Hauv cov ntsiab lus, txoj kev tshawb fawb tam sim no nrog kev sib piv ncaj qha, hnub nyoog sib piv ua rau pom qhov tsis sib haum xeeb ntawm kev humoral thiab cellular immunogenicity ntawm heterologous priming thiab boosting nyob rau hauv cov ntsiab lus ntawm SARS-CoV{106}} antigen exposures. Peb qhov kev tshawb pom tau qhia txog qhov kev paub txog kev tiv thaiv kab mob ntawm tus kheej li cas los ntawm kev tiv thaiv kab mob tiv thaiv kab mob tom qab tau txais los ntawm kev txhaj tshuaj tiv thaiv COVID{107}}. Cov ntaub ntawv hais txog kev ua tau zoo hauv ntiaj teb ntxiv thiab kev tshawb xyuas hauv chav kuaj yuav qhia ntxiv txog qhov tsim nyog tshaj plaws kev txhaj tshuaj tiv thaiv lub tswv yim rau kev tiv thaiv los ntawm SARS-CoV{110}} txawv txav, nrog rau kev cuam tshuam rau kev tsim cov tshuaj tiv thaiv tiam tom ntej.
Fig. 4. Cov tshuaj tiv thaiv kab mob hauv lub cev thaum lub sijhawm cov ntsiab lus siab tshaj plaws. (A) Cov zaus ntawm cov kab mob tshwj xeeb IFN-c ntxiv rau cov hlwb ntawm CD4 ntxiv rau T hlwb tau muab piv nrog BNT162b2/BNT162b2 (n=19), AZD1222/AZD1222 (n=18), AZD1222/BNT162b2 ( n=9), thiab kev kis kab mob ua ntej / txhaj tshuaj tiv thaiv (n=7) pab pawg ntawm lub sijhawm siab tshaj plaws. Cov ntsiab lus ntawm lub sijhawm siab tshaj plaws tau raug xaiv raws li hauv qab no: tom qab koob thib ob hauv BNT162b2 / BNT162b2, AZD1222 / AZD1222, thiab AZD1222 / BNT162b2 pawg txhaj tshuaj thiab tom qab thawj koob tshuaj hauv pawg neeg ua ntej kis kab mob / txhaj tshuaj. (B) Cov feem pua ntawm cov neeg koom nrog ntau theem ntawm kev tiv thaiv kab mob ntawm tes. Kev suav ntawm hom neeg teb (muaj zog, nruab nrab, thiab tsis muaj / tsis muaj zog) yog qhia raws li ib feem ntawm tus naj npawb ntawm cov neeg tau txais tshuaj tiv thaiv hauv txhua pab pawg. Hom neeg teb tau txiav txim los ntawm tus qhab nia feem pua suav los ntawm txhua tus neeg koom nrog txhaj tshuaj. (C) Cov zaus ntawm ntau zaus ntawm cov kab mob sib kis tshwj xeeb CD4 ntxiv rau T hlwb tsim ib qho kev sib xyaw ntawm IFN-c, IL-2, lossis TNF hauv txhua pab pawg ntawm cov neeg koom nrog txhaj tshuaj. (D) Ib feem ntawm cov kab mob tshwj xeeb CD4 ntxiv rau T hlwb yog qhov zoo rau ib tus lej ntawm cytokines. Cov ntaub ntawv raug nthuav tawm raws li txhais tau tias ± SD. Qhov tseem ceeb tau txheeb xyuas los ntawm kev xeem Mann-Whitney (A thiab C). ns, tsis tseem ceeb; *P < 0.
Ntxiv mus, cov tshuaj suav tshuaj suav tshuajcistanche tshuaj ntsuabtuaj yeem txhim kho kev tiv thaiv, Lub tshuab ntawm Cistanche deserticola hauv kev txhim kho kev tiv thaiv
cistanche ntxiv cov txiaj ntsig-yuav ua li cas ntxiv dag zog rau lub cev
Nyem qhov no mus saib Cistanche Enhance Immunity khoom
【Nug ntxiv】 Email: cindy.xue@wecistanche.com / Whats App: 0086 18599088692 / Wechat: 18599088692
Cistanche tubulosapolysaccharides tuaj yeem txhawb txoj kev loj hlob ntawm T thiab B lymphocytes, tab sis qhov kev loj hlob ntawm B lymphocytes muaj zog dua li T lymphocytes. Cistanche deserticola polysaccharides txhawb kev tso tawm ntawm cytokine IL22 los ntawm lymphocytes, uas cuam tshuam rau kev txhawb nqa splenic lymphocyte proliferation. Cistanche deserticola tuaj yeem qhib cov macrophages thiab tswj lub cev tiv thaiv kab mob. Cistanche deserticola polysaccharides, echinaside, thiab piloside muaj cov txiaj ntsig tseem ceeb ntawm kev tsim thiab kev ua haujlwm ntawm tib neeg lymphocytes. Nws tuaj yeem ua rau cov lus teb loj hlob ntawm lymphocytes, yog li txhim kho kev tiv thaiv kab mob hauv lub cev.
cistanche extract
Functional Cheebtsam ntawmCistanche tubulosatag nrho glycosides muaj qhov cuam tshuam loj rau kev rov qab los ntawm tes tom qab 60Coy hluav taws xob puas tsuaj, thiab tuaj yeem txhim kho lub cev tsis muaj zog tiv thaiv hluav taws xob puas tsuaj.
Cistanche tubulosa extract tuaj yeem tsis tsuas yog them nyiaj rau lub cev tsis muaj zog tab sis kuj txhim kho kev tiv thaiv kab mob.
Fig. 5. Cov tshuaj tiv thaiv kab mob sib txawv tawm tsam Delta uas tau txais los ntawm ntau hom kev txhawb nqa tseem ceeb. (A) Plasma samples are analyzed by plaque-reduction neutralization assays for the SARS-CoV-2 Delta variant in BNT162b2/BNT162b2 (n {{10}}), AZD1222/AZD1222 (n {{ 13}}), AZD1222/BNT162b2 (n=9), ua ntej kab mob/kev txhaj tshuaj tiv thaiv (n=11), thiab Delta-convalescent (n {{20}}) pawg. Delta-neutralizing antibodies tau muab piv rau cov pab pawg ntawm cov ntsiab lus hauv qab no: tom qab koob thib ob hauv BNT162b2 / BNT162b2, AZD1222 / AZD1222, thiab AZD1222 / BNT162b2 txhaj tshuaj tiv thaiv kab mob thiab tom qab thawj koob tshuaj hauv pawg neeg ua ntej kis kab mob / txhaj tshuaj tiv thaiv. (B) PBMCs tau txheeb xyuas los ntawm cov kab mob hauv lub cev rau IFN-c tom qab ncaj qha ex vivo stimulation siv ob qhov sib txawv ntawm S peptide pas dej ua ke suav nrog cov cheeb tsam uas tsis tau txais txiaj ntsig ntawm qhov sib txawv ntawm Wuhan thiab Delta hom kab mob hauv BNT162b2 / BNT162b2 (n=19 }), AZD1222/AZD1222 (n {{40}}), AZD1222/BNT162b2 (n=9), ua ntej kab mob / tshuaj tiv thaiv (n=7), thiab Delta-convalescent ( n=17) pawg. Qhov piv ntawm qhov zaus ntawm IFN-c-tsim CD4 ntxiv rau T hlwb tawm tsam Delta spike rau qhov zaus ntawm IFN-c-tsim CD4 ntxiv rau T hlwb tawm tsam Wuhan spike yog xam nyob rau hauv txhua pab pawg. Cov ntaub ntawv raug nthuav tawm raws li qhov ntsuas geometric ± geometric SD (A) lossis txhais tau tias ± SD (B) thiab txheeb xyuas qhov tseem ceeb siv Mann-Whitney xeem. ns, tsis tseem ceeb; *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.
Cov ntaub ntawv
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