Kev Tshawb Pom Ntawm Humoral Thiab Cellular Immune Response To Anti-SARS-CoV-2 BNT162b2 Vaccine in Breastfeeding Women And Naïve Thiab Yav Dhau Los Cov Neeg Muaj Mob

Txoj kev tshawb no tshawb nrhiav kev lom zem thiab cov lus teb ntawm tes rau cov tshuaj tiv thaiv SARS-CoV-2 BNT162b2 mRNA cov tshuaj tiv thaiv hauv cov poj niam pub niam mis thiab cov neeg tsis muaj zog thiab cov neeg mob seropositive hauv thawj rau lub hlis tom qab txhaj tshuaj. Rau caum-ib tus neeg ua haujlwm pab dawb txhaj tshuaj tiv thaiv nrog ob koob tshuaj tiv thaiv BNT162b2 mRNA tau cuv npe hauv txoj kev tshawb no. Hauv tsev tsim ELISA tau siv los ntsuas qhov ntau ntawm SARS-CoV-2 RBD-specific antibodies. Cell deg marker qhia thiab intracellular IFN- tsom xam tau ua los ntawm kev ntws cytometry. Cov concentrations ntawm IFN- , IL-6, thiab TNF tau txiav txim los ntawm ELISA. Ib qho tseem ceeb ntawm cov tshuaj tiv thaiv RBD IgG cov tshuaj tiv thaiv tau pom 14 hnub tom qab thawj koob tshuaj tiv thaiv (p< 0.0001) in serum and milk. The expression of CD28 on CD4+ T cells was significantly higher compared to baseline (p< 0.05). There was a significant increase (p≤ 0.05) in the B cell lymphocyte subset after revaccination and an increased percentage of CD80+ B cells. The expression of IFN-γ in peripheral blood lymphocytes, CD3+ T cells, and serum was significantly increased (p< 0.05). No significant difference in immune response was observed between breastfeeding women and other study participants. The anti-SARS CoV-2 BNT162b2 mRNA vaccine induced measurable and durable immune response in breastfeeding women and naïve and previously infected individuals. 

cistanche cov txiaj ntsig rau txiv neej-ua kom muaj zog tiv thaiv kab mob

Nyem qhov no mus saib Cistanche Enhance Immunity khoom

【Nug ntxiv】 Email: cindy.xue@wecistanche.com / Whats App: 0086 18599088692 / Wechat: 18599088692

1. Taw qhia 

Kev nthuav dav thoob ntiaj teb ntawm tus kab mob SARS-CoV-2 tom qab thawj kis tshwj xeeb tau sau npe thaum Lub Kaum Ob Hlis 31, 2019, hauv Wuhan, Tuam Tshoj, ua rau muaj kev sib kis thoob ntiaj teb ntawm tus kab mob Coronavirus-19 (COVID{{ 5}}), muaj nyob ib ncig ntawm 648 lab tus neeg mob thiab 6.6 lab tus neeg tuag txog thaum Lub Kaum Ob Hlis 18, 20221. Kev tuag hauv COVID-19 tau cuam tshuam nrog kev tsim tawm ntau dhau ntawm proinflammatory cytokines xws li IL-6, TNF- , thiab IL-1, lub npe hu ua "cytokine cua daj cua dub", uas tuaj yeem ua rau mob ua pa nyuaj thiab cov ntaub so ntswg loj uas ua rau ntau lub cev tsis ua haujlwm2. Txawm li cas los xij, kev txhim kho sai sai hauv kev kuaj mob, kev kho mob, thiab kev qhia txog kev txhaj tshuaj tiv thaiv yuav ua rau muaj kev poob qis hauv cov neeg mob, kev xav tau mus pw hauv tsev kho mob, thiab thaum kawg txo qis kev tuag. Hauv Serbia, thawj qhov xwm txheej sau npe tau tshwm sim thaum Lub Peb Hlis 6, 2020, thiab kev txhaj tshuaj tau pib thaum Lub Kaum Ob Hlis 24, 2020. Tam sim no, muaj plaub qhov tshuaj tiv thaiv rau cov pej xeem, Vero Cell-Inactivated (Sinopharm), Vaxzevria (ChAdOx{{ 22}}S [recombinant], AstraZeneca), Sputnik V (Gam-COVID-Vac, Gamaleya), thiab Comirnaty (BNT162b2, BioNTech-Pfizer). Ntxiv nrog rau kev tsim cov tshuaj tiv thaiv tshwj xeeb, cov tshuaj tiv thaiv kab mob zoo tiv thaiv SARS-CoV-2 yuav tsum tau ua kom muaj kev tiv thaiv ntawm tes. Te cov khoom ntawm kev tiv thaiv kab mob ntawm tes, suav nrog tus pab CD4+ thiab cytotoxic CD8+ T hlwb, ntuj tua (NK) hlwb, thiab B hlwb, nyob rau hauv thawj teev thiab hnub tom qab kis tus kab mob no yuav tsum tau txo cov tsos mob ntawm tus kab mob, tiv thaiv kev kis kab mob, mus pw hauv tsev kho mob, thiab kev tuag. Ua kom T-helper (T) hlwb tuaj yeem tua cov kab mob tsis ncaj, thiab txhawb nqa B cell ua haujlwm thiab cov tshuaj tiv thaiv kab mob, los ntawm kev tsim cov interferon- (IFN- )3,4. Nws tau pom tias T1 phenotype muaj feem cuam tshuam nrog qis qis ntawm COVID-19 kab mob5, yog li cov tswv yim rau kev tsim cov tshuaj tiv thaiv COVID-19 kuj tseem yuav xav txog qhov muaj peev xwm ua kom T cells rau IFN- ntau lawm. Cellular tiv thaiv kab mob rau SARS-CoV-2 tau tshaj tawm tias tuaj yeem kuaj tau txog li 6 lub hlis tom qab kis kab mob hauv ntau dua 90% ntawm cov tib neeg. Yog li, nws tau cia siab tias kev txhaj tshuaj tiv thaiv yuav ua rau muaj kev tiv thaiv kab mob ntawm tes uas yuav pab txhawb kev sib ntaus sib tua tiv thaiv kev sib kis. Cov txiaj ntsig tshiab tau pom tias ntxiv rau kev ua kom B hlwb nyob hauv cov chaw germinal7, cov tshuaj tiv thaiv SARS-CoV-2 mRNA yuav tsum tsim cov tshuaj tiv thaiv kab mob tshwj xeeb CD4+ thiab CD8+ T cell teb8. Txawm hais tias cov tshuaj tiv thaiv kab mob feem ntau cuam tshuam nrog kev siv tshuaj tiv thaiv, B thiab T hlwb tseem ceeb hauv kev tiv thaiv thaum rov kis tus kab mob antigens. Cov cim xeeb B thiab T hlwb no yuav tsum tau tsim los ntawm SARS-CoV-2 cov tshuaj tiv thaiv mRNA thiab yuav tsum muaj lub luag haujlwm los tswj tus kab mob rov ua dua tshiab, txwv tsis pub kis kab mob9. Txawm hais tias tsis muaj qhov tshwm sim tsis zoo tshwm sim, cov lus teb tshwj xeeb rau kev txhaj tshuaj tiv thaiv-SARS-CoV-2 hauv cov poj niam cev xeeb tub thiab pub niam mis thiab cov menyuam mos uas leej niam tau txais cov tshuaj tiv thaiv thaum lactation tseem nyob rau hauv kev tshuaj xyuas thiab tseem muaj teeb meem 10,11. Qhov kev tshawb fawb no tsom mus tshawb nrhiav thawj zaug cov lus teb txhua hli thiab cov xov tooj ntawm tes los tiv thaiv SARS-CoV-2 BNT162b2 mRNA tshuaj tiv thaiv hauv cov poj niam pub niam mis thiab hauv cov neeg tsis zoo thiab cov neeg tsis zoo, hauv thawj rau lub hlis tom qab txhaj tshuaj tiv thaiv hauv Serbia, thiab ib tug ob-xyoos qhia nws tus kheej ua raws li kev nyab xeeb mus sij hawm ntev.

Khoom siv thiab cov txheej txheem

Kawm tsim qauv thiab qauv sau thiab ua.

Tag nrho ntawm 61 tus neeg tuaj yeem pab dawb (45 SARS-CoV-2 naive, 16 SARS-CoV-2 tau zoo raws li PCR-confirmed reports) tau cuv npe hauv txoj kev tshawb fawb thiab saib xyuas nyob rau lub sijhawm txij Lub Ib Hlis mus txog Lub Kaum Ib Hlis 2{ {11}}21. Qhov nruab nrab lub sij hawm nruab nrab ntawm kev kis kab mob thiab txhaj tshuaj tiv thaiv kab mob hauv cov tib neeg yav dhau los yog 3.18 ± 0.98 lub hlis, nrog rau thaj tsam li 2-5 lub hlis. Txhua tus neeg koom nrog hnub nyoog qis dua 18 xyoo thiab tsis pom muaj kab mob ua pa thaum lub sijhawm txhaj tshuaj. Cov neeg koom nrog feem ntau yog cov neeg ua haujlwm kho mob los ntawm Lub Tsev Haujlwm rau Oncology thiab Radiology ntawm Serbia (44; 72%). Cov neeg koom tau txhaj tshuaj tiv thaiv ob koob tshuaj BNT162b2 mRNA (3 lub lis piam sib nrug). Txhua qhov kev kuaj ntshav tau ua tiav hauv cov chaw kho mob pom zoo raws li kev cai nruj thiab kev soj ntsuam. Plaub tus neeg koom yog niam pub mis niam uas tuaj yeem pab dawb piv cov ntshav thiab mis nyuj. Cov qauv tau sau tseg ntawm 6- lub sijhawm cov ntsiab lus: point 1 —prevaccination (baseline), point 2–14 hnub tom qab txhaj tshuaj tiv thaiv thawj zaug, point 3–1 lub hlis tom qab txhaj tshuaj tiv thaiv thawj zaug, point 4–2 lub hlis tom qab txhaj tshuaj tiv thaiv thawj zaug, taw tes 5-3 lub hlis tom qab txhaj tshuaj tiv thaiv thawj zaug, thiab taw tes 6-6 lub hlis tom qab txhaj tshuaj tiv thaiv thawj zaug. 10-20 mL ntawm cov ntshav peripheral raug coj mus kuaj rau txhua lub sij hawm taw tes, nrog rau 1 mL ntawm mis nyuj rau 4 tus poj niam pub niam mis. Cov ntshav tau txais los ntawm cov ntshav peripheral los ntawm centrifugation tam sim ntawd thaum ntshav kos thiab khaws cia ntawm -20 degree. Cov ntshav pob zeb liab qab (PBMC) tau cais los ntawm Hearitity ntshav, Oslo, thiab tau ntxuav peb zaug hauv RPMI 1640 Culture Nruab Nrab (COL) (Sigma, St. Louis , MO) ntxiv nrog 10% fetal calf serum (FCS) (Sigma, St. Louis, MO). Tom qab ntxuav, PBMC tau siv tam sim ntawd rau kev tshuaj ntsuam immunophenotypic. Txoj kev tshawb no tau pom zoo los ntawm Pawg Neeg Saib Xyuas Kev Ncaj Ncees ntawm Lub Tsev Haujlwm rau Oncology thiab Radiology ntawm Serbia (No. 899–01 los ntawm 01.04.2021.), thiab txhua tus neeg koom tau kos npe rau kev pom zoo. Txhua tus neeg koom nrog raug xam phaj los ntawm cov neeg ua haujlwm kho mob uas paub txog. Lub sijhawm ntev ntawm tus kheej tau tshaj tawm txog kev soj ntsuam cov kev tsis zoo tom qab txhaj tshuaj tiv thaiv tau ua nyob rau ob xyoos tom qab thawj koob tshuaj tiv thaiv.

cistanche tubulosa- txhim kho lub cev tiv thaiv kab mob

Detection and quantification of SARS-CoV-2 RBD-specific antibodies.

Kev nthuav qhia ntawm RBD ntawm SARS-CoV-2 spike protein (NCBI: YP_009724390, AA319-541) tau ua nyob rau hauv HEK-293 T cell kab raws li txheej txheem luam tawm yav dhau los12 . Cov protein recombinant tau huv si kom txog thaum homogeneity, thiab cov txiaj ntsig tau txais yog 5{{20}}0 mg rau ib L ntawm cov kab lis kev cai ntawm tes. Luv luv, cov recombinant RBD protein tau siv los npog cov roj-hauv qab 96- cov phaj zoo (Thermo Scientific NUNC-MaxiSorp, USA) ntawm qhov kawg ntawm 10 ug / mL (50 μL / zoo) hauv txheej tsis (15 mM Na2CO3 / 35 mM NaHCO3, pH 9.5) ntawm 4 degree thaum hmo ntuj. Cov phaj raug ntxuav nrog TBS uas muaj 0.05% Tween 20 (TBST) thiab thaiv nrog 1% BSA hauv TBST rau 2 h ntawm 37 degree. Diluted sera tau incubated ntawm 37 degree rau 1 h hauv TBST uas muaj 0.1% BSA, thiab tom qab ntawd cov phaj raug ntxuav nrog TBST. Rau tag nrho cov kev txiav txim siab IgG, tshis anti-Human-IgG-AP conjugated antibody (Novus Biologicals, USA) tau diluted 1/1000 hauv kev thaiv cov tshuaj thiab ntxiv rau hauv qhov dej. Tom qab incubation rau 1 h ntawm 37 degree, daim hlau raug ntxuav 5 zaug nrog TBST thiab tsim nrog 4-Nitrophenyl phosphate rau 1 h ntawm 37 degree . Lub absorbance yog ntsuas ntawm 450 nm (A450).

Flow cytometric tsom xam.

Cell surface immunophenotype of peripheral blood mononuclear cells (PBMCs) tau txheeb xyuas siv cov kev sib txuas hauv qab no ntawm cov tshuaj tiv thaiv kab mob monoclonal (mAbs): CD3FITC/CD28PE/CD4PerCP, CD80PE/CD19PerCP, CD80PE/CD14PerCP (Becton San Jose, USA). Cov qauv tau npaj raws li tau piav qhia yav dhau los13 siv 1 × 105 freshly cais PBMCs hauv 100 μL RPMI 1640 ntxiv nrog 10% Fetal Calf Serum (FCS, Sigma), incubated rau 30 min ntawm 4 degree nrog 20 μL ntawm tsim nyog mAb nrog kev sib xyaw ua ke, ntxuav ob zaug. ice-txias phosphate-buffered saline (PBS), thiab kho nrog 1% paraformaldehyde ua ntej FACS kev tshuaj xyuas. Qhov taw qhia qhov taw qhia tau raug ntsuas ntawm FACSCalibur flow cytometer (Becton-Dickinson, San Jose, USA). Tag nrho ntawm 10,000–50,{22}} gated txheej xwm txheeb xyuas raws li peripheral ntshav lymphocytes (PBLs) thiab monocytes, raws li lawv lub cev yam ntxwv, rau pem hauv ntej scatter yam ntxwv (FSC), thiab sab scatter yam ntxwv (SSC ), tau sau ib qho qauv thiab tshuaj xyuas siv CellQUEST software. Cov cell subsets tau qhia raws li qhov feem pua ​​ntawm cov ntshav peripheral.

Intracellular IFN- tsom xam.

Rau intracellular staining ntawm IFN 1 ×, 106 PBMCs tau incubated nrog Phorbol 12-myristate 13-acetate (PMA) (50 ng / mL) ntxiv rau ionomycin (500 ng / mL) rau 4 h ntawm 37 degree thiab nrog Brefeldin A (10 ug / mL) rau 3 teev dhau los, raws li tau piav qhia dhau los 14. Cells yog thawj zaug stained rau nto antigen nrog CD3 PerCP antibody, tsau thiab tom qab permeabilization nrog BD FACS permeabilizing tov 2 (BD Biosciences) stained rau anti-IFN-PE (Becton Dickinson). Intracellular IFN yog qhia raws li feem pua ​​​​hauv PBLs, nrog rau hauv CD3 T lymphocytes.

ELISA.

Qhov concentrations ntawm IFN- , IL-6, thiab TNF nyob rau hauv lub sera ntawm cov neeg koom nrog soj ntsuam tau txiav txim los ntawm kev lag luam uncoated ELISA cov khoom siv, raws li cov chaw tsim tshuaj paus cov lus qhia (Invitrogen). Qhov siab ntawm cytokines tau txiav txim siab ntawm cov ntsiab lus 1 (ua ntej txhaj tshuaj tiv thaiv), point 3 (1 hlis tom qab txhaj tshuaj tiv thaiv thawj zaug), thiab point 4 (2 lub hlis tom qab txhaj tshuaj tiv thaiv thawj zaug). Luv luv, ELISA daim hlau tau coated nrog tsim nyog cov tshuaj tiv thaiv kab mob hauv cov txheej txheem tsis zoo thiab incubated hmo ntuj ntawm 4 degree. Ua ntej, cov phaj raug ntxuav thiab thaiv nrog ELISA / ELISASPOT Diluent. Tom qab 1 h incubation, daim hlau raug ntxuav, thiab cov qauv kuaj thiab cov qauv raug ntxiv rau hauv qhov dej. Tom qab incubation, ntxuav, thiab aspiration, raws li cov chaw tsim tshuaj paus cov lus qhia, nrhiav kom tau cov tshuaj antibody ntxiv rau txhua lub qhov dej. Tom qab ntawd, cov phiaj tau ntxuav thiab aspirated; cov tshuaj avidin-HRP tau ntxiv rau hauv qhov dej thiab incubated rau 30 min. Tom qab ntawd, cov phaj raug ntxuav, thiab (3,3′,5,5′-Tetramethylbenzidine) TMB tov tau ntxiv rau txhua qhov dej. Cov phaj tau incubated rau 15 feeb ntawm chav tsev kub, thiab cov tshuaj tiv thaiv enzymatic raug txiav los ntawm kev ntxiv cov tshuaj nres. Lub absorbance tau ntsuas ntawm 450/520 nm siv Multiskan EX Termo Labsystems phaj nyeem ntawv 15. Kev txheeb cais. Cov txiaj ntsig / raug nthuav tawm raws li tus kheej qhov tseem ceeb nrog tus qauv yuam kev ntawm qhov nruab nrab (SEM). Qhov sib txawv ntawm qhov tseem ceeb tau muab piv nrog qhov tsis sib xws t-test thiab Wilcoxon kos npe-qib xeem thiab cov txiaj ntsig tau suav tias yog qhov tseem ceeb yog tias p<0.05. The analysis was performed using GraphPad Prism 9.0 (GraphPad, La Jolla, CA, USA).

cistanche tubulosa- txhim kho lub cev tiv thaiv kab mob

Cov txiaj ntsig

3.1 Kawm cov neeg koom nrog thiab ua cov kua mis / mis.

Cov yam ntxwv ntawm cov neeg koom nrog kev kawm tau nthuav tawm hauv Table 1. Los ntawm 61 tus neeg tuaj yeem pab dawb uas tau txais cov tshuaj tiv thaiv-SARS-CoV-2 BNT162b2 mRNA cov tshuaj tiv thaiv, tag nrho ntawm 344 cov qauv ntshav tau sau ntawm 6 lub sijhawm, pib los ntawm kev txhaj tshuaj tiv thaiv ua ntej. mus rau 6 lub hlis tom qab txhaj tshuaj tiv thaiv thawj zaug. Feem ntau cov neeg koom nrog kev kawm (97%) tau tshaj tawm cov kev tsis zoo hauv zos rau kev txhaj tshuaj tiv thaiv kab mob me me ntawm caj npab / xub pwg thiab qaug zog, uas kav ntev li 1-2 hnub. Tsuas yog peb tus neeg koom tau txais koob tshuaj thib ob nrog ncua sijhawm, ob qho vim muaj kev cuam tshuam tsis zoo thaum txhaj tshuaj tiv thaiv thawj zaug (dawb tawv nqaij, ua xua), thiab ib qho yog vim qhov pom ntawm cev xeeb tub tom qab thawj koob tshuaj. Tsis muaj kev kis kab mob ntawm ob koob tshuaj tiv thaiv. Tom qab 6 lub hlis ntawm kev saib xyuas, tsuas yog 3 (5%) ntawm cov neeg koom tau kis tus kab mob SARS-CoV{18}}, thiab tsis muaj hom mob hnyav uas yuav tsum tau mus pw hauv tsev kho mob. Xya tus neeg koom nrog cev xeeb tub tom qab txhaj tshuaj, ib 2 lub lis piam tom qab thawj koob tshuaj, ib 4 lub hlis tom qab thawj koob tshuaj, thiab 5 tshaj 12 lub hlis tom qab thawj koob tshuaj. Kev soj ntsuam xyuas tus kheej mus sij hawm ntev tau qhia tias tsis muaj qhov cuam tshuam txog kev txhaj tshuaj tiv thaiv txog li ob xyoos tom qab thawj koob tshuaj, hauv cov poj niam pub niam mis lossis lwm tus neeg koom nrog kev kawm.

Quantification of SARS-CoV-2 RBD-specific antibodies in the serum and milk of study.

Kev tshuaj xyuas cov qib tom qab txhaj tshuaj tiv thaiv-RBD IgG cov tshuaj tiv thaiv kab mob hauv cov ntshav, qhov nce tseem ceeb hauv cov tshuaj tiv thaiv RBD IgG tau pom txawm tias 14 hnub tom qab thawj koob tshuaj tiv thaiv hauv tag nrho pawg tshuaj ntsuam xyuas piv rau qib IgG ua ntej txhaj tshuaj (17.47 ± 51.49 AU /mL vs. 7828.28 ± 24,157.29 AU/mL, p<0.0001) (Fig. 1a). Te serum levels of anti-RBD IgG continued to rise to 2 months post-vaccination, when a decrease was detected, which lasted up to 6 months, steadily. The levels of anti-RBD IgG antibodies were compared at each time point between naïve and previously infected individuals (Fig. 1b-c), and it was determined that the difference was statistically significant at baseline (point 1), as previously infected individuals had a higher level of antibodies before vaccination (7.23±0.77 AU/mL vs. 54.47±101.40 AU/mL, p<0.01). The difference was statistically significant also in points 2 (3979.48±3277.27 AU/mL vs. 22,581.99±49,570.63 AU/mL, p<0.05), 5 (2369.16±1934.31 AU/ mL vs. 6366.83±6875.85 AU/mL, p<0.01), and 6 (461.96±375.41 AU/mL vs. 766.04±317.35 AU/mL, p<0.05). The decline in antibody levels had the same dynamics in both groups but remained at higher levels in previously infected individuals for up to 6 months. No other analyzed parameters were correlated with a significantly different level of antibodies in serum (age, gender, smoking status). When comparing levels of anti-RBD IgG antibodies in other participants and breastfeeding women (Fig. 1d-e), no significant differences in serum antibody levels were observed in any of the comparisons. Anti-RBD IgG antibodies were also detected in the milk of 4 breastfeeding women (Fig. 1f). In lower levels, they presented with the same dynamics of rising and decline as detected in the serum. Comparing the levels of anti-RBD IgG antibodies in milk at each time point to baseline, (Fig. 1f), it was determined that the difference was statistically significant at points 2 (6.57±0.77 AU/mL vs. 152.13±35.83 AU/ mL, p<0.01) and 6 (6.57±0.77 AU/mL vs. 117.31±25.64 AU/mL, p<0.01).

Table 1. Cov yam ntxwv ntawm cov neeg koom nrog kev kawm.

Daim duab 1. Serum anti-RBD IgG antibody qib nyob rau hauv (a) tag nrho pawg soj ntsuam, (b naïve, c) yav tas los cov neeg muaj tus kab mob, (d) tag nrho pab pawg neeg tsis pub niam mis, (e) cov poj niam pub niam mis, thiab (f) nyob rau hauv lub cov kua mis ntawm cov poj niam pub niam mis. Cov txiaj ntsig tau nthuav tawm raws li tus kheej qhov tseem ceeb nrog tus qauv kev ua yuam kev ntawm qhov nruab nrab (SEM) ntawm peb qhov kev hloov pauv ywj pheej. Qhov sib txawv ntawm qhov tseem ceeb tau muab piv nrog kev siv qhov tsis sib xws t-test thiab cov txiaj ntsig tau suav tias yog qhov tseem ceeb yog tias p<0.05. * p<0.05; **p<0.01; *** p<0.0001.

Flow cytometric thiab intracellular IFN- kev tshuaj xyuas.

Cov ntaub ntawv tau txais los ntawm fow cytometric tsom xam pom tias qhov kev qhia ntawm CD28 ntawm CD4+ T hlwb hauv cov ntshav peripheral ntawm 2 lub hlis tom qab qhov koob tshuaj thib ob tau nce siab dua piv rau cov txiaj ntsig ua ntej txhaj tshuaj tiv thaiv (42.84 ± 5.37% vs. 37.75 ± 5.96%, p<0.05, Wilcoxon signed-rank test) (Fig. 2a). Tere was a signifcant increase (p≤0.05, Wilcoxon signed rank test) in the prevalence of B cell lymphocyte subset (CD19+) from 6.87±1.17% to 8.73±1.54%, two months afer revaccination, as well as an increased percentage of CD80+ B cells from 1.72±0.28% to 1.99±0.28% (Fig. 2b). Furthermore, fve weeks afer revaccination, a signifcant (p≤0.05, Wilcoxon signed rank test) increase in the percentage of CD14+CD80+ cells from 1.15±0.38% to 5.87±0.95% was detected in the monocyte gate (Fig. 2c). Te expression of IFN-γ in PBLs, as well as in CD3+ T cells was signifcantly (p < 0.05, Wilcoxon signed rank test) increased at 1 week afer the second vaccine dose (1.84 ± 0.13% in PBL and 1.32 ± 0.10% in CD3+ T cells) compared to pre-vaccination baseline values (0.88 ± 0.13% in PBL and 0.72 ± 0.12% in CD3+ T cells) (Fig. 3a). Furthermore, serum levels of IFN-γ were signifcantly increased in all participants from the initial value of 16.69±0.29 pg/mL to 17.72±0.41 pg/mL (p<0.05, Wilcoxon signed rank test) (Fig. 3b), as well as in naive from 16.55±1.77 pg/mL to 17.26±2.53 pg/mL and in a group and previously infected individuals, from 15.93±2.01 pg/mL to 19.90±4.32 pg/mL at 1 week afer revaccination (Fig. 3c). Tere was no signifcant (p>0.05, Wilcoxon kos npe rau qeb xeem) qhov sib txawv ntawm cov ntshav ntshav ntawm IL-6 thiab TNF- 1 lub lim tiam thiab fve lub lis piam afer koob tshuaj thib ob piv rau cov nqi txhaj tshuaj ua ntej hauv tag nrho pab pawg, nrog rau cov neeg tsis paub qab hau los yog yav tas los muaj tus kab mob (Ntxiv Fig. 1a–d).

Kev sib tham

Tus kab mob SARS-CoV-2 tus kab mob ua pa tau ua rau muaj kev cuam tshuam loj heev rau ntau yam ntawm lub neej niaj hnub, suav nrog cov teeb meem hauv zej zog, kev kawm, thiab kev noj qab haus huv uas tsis cuam tshuam ncaj qha rau COVID-19 kab mob nws tus kheej16–18 . Kev txhaj tshuaj tiv thaiv thoob ntiaj teb yog qhov tsim nyog los txhawb kev ntsuas nyob deb hauv kev tiv thaiv tus kab mob, thiab ntau cov kev tshawb fawb tshawb fawb txog kev ua tau zoo thiab kev ua tau zoo ntawm ntau hom tshuaj tiv thaiv uas tau muab faib thoob ntiaj teb thaum xyoo 2021. Hauv Serbia, tsuas yog cov lus ceeb toom ib ntus ntawm kev tiv thaiv kab mob 2 thiab 3 lub hlis tom qab txhaj tshuaj tiv thaiv tam sim no19 ,20 thiab ua raws li cov ntaub ntawv qhia hauv qhov kev tshawb fawb no. Hauv peb pawg neeg soj ntsuam txog li 6 lub hlis tom qab txhaj tshuaj, 100% seroconversion tus nqi tau kuaj pom tom qab thawj koob tshuaj tiv thaiv. Tsuas yog 5% ntawm cov neeg koom yuav tsum tau txais koob tshuaj tiv thaiv thib ob nrog ncua sijhawm. Tsis muaj ntawv ceeb toom ntawm SARS-CoV-2 kis ntawm ob koob tshuaj tiv thaiv. Txog rau lub hlis ntawm kev saib xyuas, tsuas yog 5% ntawm cov neeg koom tau kis tus kab mob, tsis tas yuav mus pw hauv tsev kho mob. Titers ntawm anti-RBD SARS-CoV-2 IgG cov tshuaj tiv thaiv tau ntau dua piv rau cov hauv paus txawm tias tom qab thawj koob tshuaj tiv thaiv, uas ua rau muaj kev xav tias kev siv tshuaj tiv thaiv BNT162b2 mRNA yog ib txoj hauv kev zoo rau cov lus teb ceev ceev rau cov thawj coj. kab mob. Cov qib IgG cov ntshav txuas ntxiv nce mus txog 2 lub hlis tom qab txhaj tshuaj tiv thaiv thaum kuaj pom qhov txo qis mus txog rau lub sijhawm soj ntsuam ntawm 6 lub hlis. Yav dhau los cov neeg muaj tus kab mob no tau pom tias muaj IgG titers siab dua piv rau cov tib neeg uas tsis muaj hnub nyoog txog 6 lub hlis, uas yog tib yam uas ua rau muaj cov tshuaj tiv thaiv sib txawv. Anti-RBD IgG cov tshuaj tiv thaiv kuj tau kuaj pom hauv cov kua mis ntawm cov poj niam pub niam mis hauv peb thiab qee qhov kev tshawb fawb yav dhau los21, nrog rau kev sib txuam titer dynamics xws li hauv cov ntshav. Cov ntawv tshaj tawm zoo sib xws tau luam tawm rau IgA cov tshuaj tiv thaiv tom qab kev kis tus kab mob 22. Raws li cov ntaub ntawv txwv tam sim no muaj nyob rau ntawm qhov txaus ntshai thiab cov txiaj ntsig ntawm kev txhaj tshuaj tiv thaiv ntawm cov poj niam pub niam mis, cov txiaj ntsig no tau cog lus nyob rau hauv qhov pom ntawm qhov muaj peev xwm txhaj tshuaj tiv thaiv kab mob ntawm cov menyuam mos uas pub mis niam, txawm tias tom qab 6 lub hlis tom qab txhaj tshuaj tiv thaiv niam. Tsis muaj qhov sib txawv tseem ceeb hauv cov tshuaj tiv thaiv kab mob hauv cov ntshav tau pom ntawm cov neeg tsis zoo lossis yav dhau los muaj tus kab mob thiab cov poj niam pub niam mis, txhawb kev soj ntsuam tias cov lus teb rau cov tshuaj tiv thaiv SARS-CoV-2 tsis cuam tshuam los ntawm lactation. Cov lus pom zoo tam sim no hais tias kev txhaj tshuaj tiv thaiv yuav tsum raug txiav txim siab rau txhua tus neeg muaj hnub nyoog 6 hli thiab tshaj saud, suav nrog cov uas cev xeeb tub lossis sim xeeb tub tam sim no lossis yav tom ntej thiab pub niam mis, tsis hais txog lawv yav dhau los COVID-19 tus kab mob xwm txheej23. Peb txoj kev tshawb fawb no txhawb nqa lub nra ntawm cov pov thawj24 qhia tias tsis muaj kev phom sij tam sim rau cov poj niam pub niam mis uas tau txais tshuaj tiv thaiv SARS-CoV-2 lossis lawv cov menyuam mos noj mis. Tsis tas li ntawd, xya tus neeg koom nrog tau cev xeeb tub tom qab txhaj tshuaj, ib 2 lub lis piam tom qab thawj koob tshuaj, ib 4 lub hlis tom qab thawj koob tshuaj, thiab 5 tshaj 12 lub hlis tom qab thawj koob tshuaj. Tsis ntev los no tau ua qhov kev sib tham ntev ntev ntawm cov neeg koom nrog kev tshawb fawb tau lees paub tias tseem tsis tau muaj kev phom sij rau cov poj niam pub niam mis lossis lawv cov menyuam mos noj mis, lossis lwm tus neeg koom nrog, ob xyoos tom qab tau txais tshuaj tiv thaiv SARS-CoV-2.

Daim duab 2. Feem pua ​​ntawm (a) CD3+CD28+ thiab CD4+CD28+ T lymphocytes, (b) CD19+ thiab CD{{6 }}CD80+ B lymphocytes, (c) CD14+CD80+ monocytes hauv cov ntshav peripheral. Te cov txiaj ntsig tau nthuav tawm raws li tus kheej qhov tseem ceeb nrog qhov ntsuas ± tus qauv kev ua yuam kev ntawm qhov nruab nrab (SEM). Qhov sib txawv ntawm qhov tseem ceeb tau muab piv nrog Wilcoxon kos npe-qib xeem thiab cov txiaj ntsig tau suav tias yog qhov tseem ceeb yog tias p<0.05. * p<0.05.

Cov tsos ntawm cov kev hloov pauv tshiab ntawm kev txhawj xeeb nrog rau qhov muaj nyob ntawm cov lus ceeb toom ntawm kev poob qis hauv kev tiv thaiv SARS CoV-2 qib tshuaj tiv thaiv kab mob tom qab kev kis tus kab mob thiab tshuaj tiv thaiv25 tau ua rau muaj kev tsis paub meej txog lub luag haujlwm ntawm cov khoom tiv thaiv ntawm tes. Qee qhov kev tshawb fawb tshawb fawb txog kev tiv thaiv kab mob ntawm cov neeg txhaj tshuaj hauv Serbia tau tshaj tawm tsuas yog kev tiv thaiv kab mob humoral19,20. Hauv txoj kev tshawb no, kev nthuav qhia ntau ntxiv ntawm costimulatory receptors CD28 ntawm CD4+ T hlwb thiab CD80 ntawm B hlwb raug kuaj pom 2 lub hlis tom qab kev tswj hwm ntawm koob tshuaj thib ob. Tsis tas li ntawd, qhov kev qhia ntawm CD80 ntawm monocytes tau nce 1- hli tom qab txhaj tshuaj tiv thaiv tiav.

T cell proliferation thiab sib txawv rau hauv efector lossis lub hlwb nco xav tau kev nthuav qhia antigen, co-stimulation, thiab cytokines. Qhov zoo tshaj plaws-tiv thaiv co-stimulators ntawm T hlwb yog khub ntawm molecules, B7-1 (CD80) thiab B7-2 (CD86). Tey feem ntau qhia txog cov tshuaj tiv thaiv kab mob (APCs) xws li dendritic hlwb, B hlwb, macrophages, monocytes, thiab T-cells. Lawv cov lus qhia ntawm monocytes kuj tseem ceeb rau kev ua kom cov lymphocytes thiab yoog raws kev tiv thaiv kab mob26. Ob lub ntsiab receptors tam sim no nyob rau saum npoo ntawm T lymphocytes uas khi CD80 thiab CD{11}} yog CD28, thiab cytotoxic T-lymphocyte txuam protein 4 (CTLA{15}}). Kev khi rau CD28 activates lymphocytes thiab thiaj li txhim kho lub cev tiv thaiv kab mob27. Te cov txiaj ntsig tau txais hauv txoj kev tshawb fawb no qhia tau tias CD4+ T hlwb tau qhib los ntawm S antigen-derived epitopes nthuav tawm ntawm cov kab mob B thiab monocytes 2 lub hlis tom qab txhaj tshuaj thib ob. Ntau cov ntaub ntawv qhia tias CD4 T hlwb feem ntau tau ua haujlwm tom qab mRNA tshuaj tiv thaiv 28,29, thaum nyob rau hauv qee qhov kev tshawb fawb CD4 thiab CD8 T hlwb tau tshaj tawm tias muaj kev sib npaug thiab qhib tau30. Tan et al. Tsis ntev los no tau pom tias ntawm 3 lub hlis tom qab txhaj tshuaj tiv thaiv, qhov nruab nrab ntawm Spike-specific T cells yog sib npaug rau qhov uas tau kuaj pom hauv cov neeg mob convalescent tib lub sijhawm tom qab SARS-CoV-2 kab mob31. Tsis tas li ntawd, cov khoom ntawm kev tiv thaiv kev tiv thaiv kab mob (ob qho tib si hauv yav dhau los muaj kab mob thiab tshuaj tiv thaiv) zoo li tswj hwm nws tus kheej 6,32,33 thiab tsis muaj kev sib raug zoo ntawm cov tshuaj tiv thaiv kab mob tiv thaiv kab mob thiab T cell zaus. Tsis tas li ntawd, cov tshuaj tiv thaiv mRNA tam sim no ua rau cov lus teb tiv thaiv kab mob nyob rau hauv Spike protein. Txawm li cas los xij, qhov muaj peev xwm tiv thaiv lub luag haujlwm ntawm T hlwb tshwj xeeb rau lwm cov txheej txheem thiab cov protein tsis zoo kuj yuav tsum tau soj ntsuam34. Koj lub tswv yim tias cov tshuaj tiv thaiv kab mob poly antigenic tuaj yeem tswj hwm kev tiv thaiv kab mob ntau dua li cov tshuaj tiv thaiv kab mob monoantigenic, xws li tshuaj tiv thaiv kab mob Spike protein-based, tej zaum yuav muaj qhov laj thawj zoo35,36.

Daim duab 3. (a) Kev nthuav qhia ntawm IFN- nyob rau hauv tag nrho thiab CD3+ T peripheral ntshav lymphocytes. Qib ntshav ntawm IFN- nyob rau hauv (b) tag nrho pawg neeg soj ntsuam, (c) cov neeg tsis paub qab hau thiab yav tas los muaj tus kab mob. Cov txiaj ntsig tau nthuav tawm raws li tus kheej qhov tseem ceeb nrog tus qauv yuam kev ntawm qhov nruab nrab (SEM). Qhov sib txawv ntawm qhov tseem ceeb tau muab piv nrog Wilcoxon kos npe-qib xeem thiab cov txiaj ntsig tau suav tias yog qhov tseem ceeb yog tias p<0.05. * p<0.05.

Nyob rau hauv txoj kev tshawb no nce qib ntawm IFN- tau kuaj pom nyob rau hauv tag nrho cov lymphocytes thiab hauv CD3+ T hlwb 7 hnub tom qab ua tiav kev txhaj tshuaj. Tsis tas li ntawd, kev nce qib ntawm IFN- hauv cov ntshav ntawm txhua tus neeg tau txhaj tshuaj tau pom, ob qho tib si hauv SARS-CoV-2 tsis zoo thiab yav dhau los cov neeg kis mob 7 hnub tom qab txhaj tshuaj tag nrho. Yog li, mRNA-raws li tshuaj tiv thaiv-induced Spike-specific T hlwb uas tsim tawm IFN- . IFN- yog ib qho tseem ceeb cytokine nrog cov tshuaj tiv thaiv kab mob thiab tau pom tias inhibit qhov kev rov ua dua ntawm SARS-CoV-28. Qhov kev tshem tawm sai sai ntawm IFN- los ntawm BNT162b2 tshuaj tiv thaiv tau pom nyob rau hauv txoj kev tshawb fawb no qhia tau hais tias T cell tiv thaiv kab mob tiv thaiv kab mob SARS-CoV-2. Cov tshuaj tiv thaiv kab mob tiv thaiv kab mob tshwm sim los ntawm SARS-CoV-2 kuj suav nrog kev tsim ntau cov cytokines proinflammatory, feem ntau IL-6 thiab TNF- thiab cov kev hloov pauv hauv lawv cov qib yuav cuam tshuam nrog kev tshwm sim ntawm tus kab mob. Cov mob hnyav thiab tuag taus ntawm COVID-19 tau tshaj tawm hauv cov tib neeg uas muaj cytokine ntau dua 37. Txawm li cas los xij, hauv txoj kev tshawb no, tsis muaj qhov sib txawv tseem ceeb hauv qib ntshav ntawm IL-6 thiab TNF- tau kuaj pom 7 hnub thiab txog li 1 lub hlis tom qab txhaj tshuaj tag nrho, uas yuav tshwm sim los ntawm cov yam ntxwv tshwj xeeb thiab lub sijhawm ntawm kev kuaj.

Cov ntaub ntawv no sawv cev rau thawj cov ntaub ntawv tshaj tawm txog kev tiv thaiv kab mob ntev mus rau hauv tus account ob qho tib si humoral thiab cellular tivthaiv, uas tsom rau cov poj niam pub niam mis. Qhov no tej zaum yuav pab tau tshwj xeeb tshaj yog rau yav tom ntej meta-kev soj ntsuam ntawm qhov no thiab lwm yam rhiab neeg subgroups, raws li cov ntaub ntawv los ntawm lub Balkan cheeb tsam nyob rau hauv Slavic pej xeem yog feem ntau ploj los ntawm ntau lub teb chaws kev siv zog.

cistanche tubulosa- txhim kho lub cev tiv thaiv kab mob

Cov lus xaus

Cov tshuaj tiv thaiv kab mob SARS-CoV-2 BNT162b2 mRNA txhaj tshuaj tiv thaiv kev ntsuas tau thiab ua kom muaj kev lom zem thiab cov lus teb ntawm tes hauv cov poj niam pub niam mis thiab ob tus neeg tsis paub qab hau thiab yav dhau los tus kab mob hauv thawj rau lub hlis tom qab txhaj tshuaj tiv thaiv hauv Serbia. Tsis muaj qhov cuam tshuam loj heev rau kev txhaj tshuaj tiv thaiv, thiab tsuas yog 5% ntawm cov neeg koom tau kis tus kab mob SARS-CoV-2 thawj rau lub hlis tom qab txhaj tshuaj tiv thaiv, tsis tas yuav mus pw hauv tsev kho mob. Tsis muaj kev phom sij rau cov poj niam pub niam mis lossis lawv cov menyuam mos noj mis tau tshaj tawm ob xyoos tom qab tau txais cov tshuaj tiv thaiv SARS-CoV{10}}. Cov kev tshawb fawb tom ntej hauv thaj chaw yuav tsum tsom mus rau kev tshawb fawb tshuaj tiv thaiv thiab cov tswv yim txhim kho uas tuaj yeem ua rau COVID-19 thiab muaj peev xwm kis tau zoo sib xws nyob rau hauv kev tswj hwm sai thiab kav ntev. Kev siv zog kuj tseem yuav tsum tau nqis peev los muab cov lus qhia raws li kev paub, kom daws cov ntaub ntawv tsis tseeb tshwj xeeb tshaj yog nyob ib puag ncig cov neeg muaj kev ntxhov siab xws li cov poj niam pub niam mis, pab txhawb kev nkag mus rau cov tshuaj tiv thaiv thaum muaj kev xav tau siab, thiab txhawb kev ntseeg siab hauv kev tshawb fawb.

cistanche cov txiaj ntsig-ua kom muaj zog tiv thaiv kab mob

Cov ntaub ntawv

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