Kev Tshuaj Xyuas Kev Tiv Thaiv Kab Mob Ntawm SARS-CoV-2 Infection And Vaccine Serology: Innate And Adaptive Responses To MRNA, Adenovirus, Inactivated And Protein Subunit Vaccines Part 1

Abstract:

Tus kab mob coronavirus 2019 (COVID-19) kis thoob qhov txhia chaw yog tshwm sim los ntawm tus mob hnyav ua pa nyuaj ua pa mob coronavirus 2 (SARS-CoV-2) tus kab mob, uas yog txhais los ntawm nws qhov zoo-kev paub zoo ib leeg-stranded RNA (ssRNA) qauv. Nws yog nyob rau hauv qhov kev txiav txim Nidovirales, suborder Coronaviridae, genus Betacoronavirus, thiab sub-genus Sarbecovirus (lineage B), ua ke nrog ob hom puav-derived nrog 96 feem pua ​​​​genomic homology nrog rau lwm cov kab mob coronaviruses (BatCoVand RaTG13).

Txog tam sim no, ob hom Alphacoronavirus, HCoV-229E thiab HCoV-NL63, nrog rau tsib Betacoronaviruses, HCoVHKU1, HCoV-OC43, SARS-CoV, MERS-CoV, and SARS-CoV-2, tau lees paub tias yog human coronaviruses (HCoVs). SARS-CoV-2 tau ua rau ntau tshaj li rau lab tus neeg tuag thoob ntiaj teb txij li xyoo 2019. Qhov tshwm sim ntawm tus kab mob tshiab no tau txhais los ntawm nws qhov kev sib kis loj thiab sib txawv (RT) thiab sib koom ua ke asymptomatic thiab cov tsos mob nthuav tawm hauv thiab thoob plaws cov tsiaj txhu. , uas muaj kev cuam tshuam ntev.

Kev sib raug zoo ntawm tus kab mob Acoronavirus thiab kev tiv thaiv kab mob yog qhov nyuaj thiab nyob ntawm ntau yam, suav nrog cov xwm txheej ntawm tus neeg lub cev tiv thaiv kab mob, kev hloov pauv tus kab mob, thiab kev siv tshuaj tiv thaiv. Feem ntau, cov tib neeg uas muaj kev tiv thaiv kab mob muaj zog muaj cov tsos mob tsawg dua tom qab kis kab mob thiab rov zoo dua. Txawm li cas los xij, vim tias cov kab mob alphacoronavirus hloov pauv tas li, txawm tias cov tib neeg muaj kev tiv thaiv kab mob muaj zog tuaj yeem kis tus kab mob tshiab. Tsis tas li ntawd, qhov ua tau zoo ntawm cov tshuaj tiv thaiv nws txawv raws li tus kab mob strain mutates, yuav tsum tau hloov kho tas li thiab hloov kho. Yog li peb yuav tsum txhim kho peb txoj kev tiv thaiv. Cistanche tuaj yeem txhim kho kev tiv thaiv zoo. Nqaij tshauv muaj ntau yam khoom xyaw lom, xws li polysaccharides, ob lub nceb, Huang Li, thiab lwm yam. Cov khoom xyaw no tuaj yeem txhawb nqa ntau hom nqaij hauv lub cev. hlwb, nce lawv cov kev tiv thaiv kab mob.

Nyem cistanche tubulosa cov txiaj ntsig

Cov kev kho mob tam sim no feem ntau yog txhawm rau txo qhov hnyav ntawm COVID-19 mus pw hauv tsev kho mob thiab cov tsos mob ntawm tus kab mob, tiv thaiv kev kis tus kab mob los ntawm kev mob mus ntev rau cov neeg tsis muaj zog. Tam sim no, muaj kev cuam tshuam pharmacological nrog rau cov tshuaj tiv thaiv thiab lwm yam, nrog rau kev tshawb fawb tsis tu ncua. Tib txoj kev coj ncaj ncees rau kev txhim kho tsiaj tiv thaiv kab mob yog tsim thiab muab tshuaj tiv thaiv thiab kho mob uas tuaj yeem txhim kho cov lus teb hauv lub cev thiab hloov kho tib lub sijhawm. Yog li, ntau cov tshuaj tiv thaiv tau tsim los muab kev tiv thaiv kab mob SARS-CoV-2-induced COVID-19 kab mob.

Qhov kev ntsuam xyuas thawj zaug ntawm COVID-19 cov tshuaj tiv thaiv tau pib nyob ib ncig ntawm 2020, tom qab ntawd los ntawm kev sim tshuaj kho mob thaum muaj kev sib kis nrog cov pej xeem tsis tu ncua kev saib xyuas tsis zoo los ntawm cov koom haum tswj hwm. Yog li ntawd, kev ruaj khov thiab kev tiv thaiv kab mob uas tau muab los ntawm cov tshuaj tiv thaiv tam sim no yuav tsum tau ua tus yam ntxwv ntxiv nrog cov ntaub ntawv muaj ntau dua, raws li tau hais hauv daim ntawv no. Thaum siv thoob ntiaj teb, cov tshuaj tiv thaiv no tuaj yeem tsim cov qauv tsis paub txog cov tshuaj tiv thaiv kab mob lossis kev nco B thiab T cell cov lus teb uas yuav tsum tau tshawb fawb ntxiv, qee qhov tam sim no tuaj yeem muab piv rau hauv chav kuaj thiab cov kev tshawb fawb pej xeem ntawm no.

Ob peb cov tshuaj tiv thaiv kab mob COVID-19 tau raug nthuav tawm hauv kev sim tshuaj ntsuam xyuas lawv txoj kev nyab xeeb thiab kev ua tau zoo, ua rau cov tshuaj tiv thaiv cellular tsim los ntawm kev sib cuam tshuam ntawm tes B thiab T cell uas tiv thaiv kab mob. Cov lus teb no yog txhais los ntawm cov kab mob tshwj xeeb cov tshuaj tiv thaiv kab mob (anti-N lossis anti-S antibodies), nrog rau B thiab T cell characterization tab tom tshawb fawb ntau. Hauv tsab xov xwm no, peb tshuaj xyuas plaub hom tshuaj tiv thaiv COVID-19 tam sim no, muab piv rau lawv cov tshuaj tiv thaiv kab mob thiab cov xov tooj ntawm tes uas cuam tshuam nrog tus kabmob coronavirus hauv ntau qhov kev tshawb fawb pej xeem.

Ntsiab lus:

COVID-19 tshuaj tiv thaiv; Pfizer; BioNTech; Oxford-AstraZeneca; Sinopharm; Novavax; antibody teb; T cell; B cell; neutralizing cov tshuaj tiv thaiv; adaptive tiv thaiv kab mob; kev tiv thaiv kab mob.

1. Taw qhia

Tus kab mob COVID-19 tam sim no uas tau pib xyoo 2019 yog tshwm sim los ntawm tus kab mob tshiab SARS-CoV-2 tus kab mob uas ua rau kis tau tus kab mob feem ntau los ntawm kev ua pa, nrog rau kev nthuav qhia kev kho mob sib txawv cuam tshuam los ntawm co-morbidities thiab lwm yam tsis paub ( Piv txwv li, kab mob hloov pauv lossis npib nyiaj npib). Immunological teb yog sib txawv thiab cuam tshuam los ntawm cellular thiab molecular nrog rau cov yam ntxwv ntawm caj dab sib txawv yuav tsum tau tham nyob rau hauv kom meej nyob rau hauv peb daim ntawv tom ntej no, ib ntus txoj cai "Innate thiab Adaptive Immune Biomolecular Mechanisms los ntawm Case Study nyob rau hauv SARS-CoV-2Pathogenesis".

SARS-CoV-2 virion yog tsim los ntawm plaub cov qauv muaj protein ntau: spike (S protein), nucleocapsid (N protein), hnab ntawv (E protein), thiab daim nyias nyias (M protein) [1–3]. Lub genome loj ntawm SARS-CoV-2 yog kwv yees li 30 kilobases thiab yog txhais los ntawm qhib kev nyeem ntawv (ORFs) uas encode 16 non-structural proteins (NSP) tsim nyog rau amino acid synthesis ntawm kab mob txuas, nkag mus, uncoating, replication , sib dhos, thiab virion tso [4]. SARS-CoV-2 kis mus rau ntau lub hlwb ntawm txoj kev ua pa, pib siv ACE2 ua tus receptor predominant rau receptor-mediated nkag [5].

Txawm li cas los xij, lwm cov receptors muaj feem cuam tshuam rau hauv kev sib kho ntawm tes taw qhia thiab nkag mus, suav nrog hom II transmembrane protease (TMPRSS2), asialoglycoprotein receptor -1 (ASGR1), kringle-muaj transmembrane protein 1 (KREMEN1), dipeptidyl peptidase 4 (DPP4). ), neuropilin (NRP1), thiab CD147 ntawm lwm tus. Cov receptors no tab tom tos kev tshawb fawb ntxiv, thaum lwm tus tab tom tshawb xyuas [6–9]. Tib neeg kis tus kab mob COVID-19 tso tawm ob qho tib si asymptomatic thiab cov tsos mob hnyav rau cov kab mob ntev, zoo li lwm cov kab mob coronaviruses (SARS-CoV-1 thiab MERS) thiab lwm yam kab mob ua pa raws caij nyoog uas muaj xws li mob khaub thuas thiab kab mob ua pa syncytial ( RSV) uas ua rau muaj ntau yam tsos mob thaum kis kab mob [10–12]. Tus nqi ntawm tus kab mob thiab kev tuag yog txhais los ntawm R0 (kev loj hlob) thiab tus kab mob tuag taus (IFR). Tam sim no R0 kwv yees sib txawv ntawm 1.47 mus rau 1.86, nrog IFR kwv yees li ntawm 0.49 txog 2.53.
Txawm li cas los xij, cov txiaj ntsig no cuam tshuam los ntawm kev hloov pauv ntawm cov protein sib txawv, nrog rau cov tshuaj tiv thaiv tau rov tsim dua nrog rau lwm cov kev kho niaj hnub no [13,14]. Thaum Lub Peb Hlis 2020, Lub Koom Haum Saib Xyuas Kev Noj Qab Haus Huv Ntiaj Teb tau tshaj tawm COVID-19 kom muaj kev sib kis [1–3,15–17]. Yog li ntawd, cov tshuaj tiv thaiv sawv cev rau thawj qhov kev tiv thaiv kab mob-kev tswj hwm kev tiv thaiv kev tiv thaiv, tiv thaiv los ntawm kev txhim kho kev tiv thaiv kev tiv thaiv SARS-CoV-2 thiab txo tus kab mob lub nra ntawm kev noj qab haus huv [18,19]. SARS-CoV-2 ua rau tus kab mob COVID{17}} feem ntau yog los ntawm S-protein, uas tus kab mob nkag mus rau hauv hlwb ntawm angiotensin-hloov enzyme 2 receptor (ACE2) [20]. Neutralizing antibodies (nAbs) yog tsim tawm los tiv thaiv cov epitopes tshwj xeeb ntawm S, N, M, thiab E protein antigens thaum SARS-CoV{24}} kab mob [21–23]. Kev npaj tshuaj tiv thaiv thiab kev tshawb fawb tau tsom mus rau S protein ua lub hom phiaj tseem ceeb rau kev thaiv kev nkag mus rau receptor-mediated, txawm hais tias N protein kho tau tsim [24]. S proteins yog tsim rau hauv S1 subunit thiab S2 subunit uas muaj nyob rau hauv lub hnab ntawv viral li homotrimers.

Lub S1 subunit txiav txim siab receptor lees paub los ntawm receptor-binding domain (RBD), whereas S2 subunit yog lub luag haujlwm rau daim nyias nyias fusion thiab nkag los ntawm kev khi rau angiotensin-hloov enzyme 2 (ACE2) uas npog tib neeg cov hlab ntsws epithelial hlwb, uas ua rau muaj qhov ua tau zoo. ntawm tus kab mob RNA txuas thiab intracellular replication uas tshwm sim thaum SARS-CoV-2 kab mob [25,26]. S1 domain suav nrog lub teeb liab peptide (SP), RBD, thiab S2 fusion protein. S2 domain encompasses ntau lwm yam proteins xws li N-terminal domains (NTD), RBD, thiab C-terminal domains (CTD1 thiab CTD2).

S2 domain muaj ntxiv fusion peptides (FP) nrog rau ob lub heptad repeat domains (HR1 thiab HR2), lub transmembrane domain, thiab C-terminal domain nrog furin cleavage site [27,28]. S protein fusion kuj tseem tuaj yeem siv TMPRSS2 thiab endosomal cysteine ​​proteases xav los kho SARS-CoV-2 nkag mus nyob ntawm qhov sib txawv thiab ACE2 conformation [29,30]. Ntau cov tshuaj tiv thaiv COVID-19 tam sim no tau tsim tawm uas ua rau B cell-evoked IgG anti-S protein cov tshuaj tiv thaiv uas ua rau pom kev tiv thaiv kab mob ntev [31].

Raws li ntawm 30 Lub Kaum Hli 2022, muaj 276 qhov kev kho mob muaj peev xwm thiab 332 kev kho mob tab tom txhim kho rau COVID-19 tiv thaiv, raws li cov ntaub ntawv tam sim no los ntawm Milken Institute (milkeninstitute.org). Ntawm cov no, 10 qhov tshuaj tiv thaiv tau pib sim cov neeg laus hauv cov theem sib txawv [26]. Kev tshawb nrhiav thiab kev tsim cov txheej txheem ntawm tes thiab cov proteins koom nrog hauv kev tsim tshuaj tiv thaiv tau dhau los ua qhov tseem ceeb los txhim kho kev nkag siab ntawm COVID-19 pathogenesis, uas yuav ua rau muaj kev nthuav dav hauv kev nkag siab ntawm lwm cov kab mob. Tom qab kev sim tshuaj, nws tau pom tias nAbs thiab non-nAbs ua rau lub cev tiv thaiv kab mob humoral thiab cellular, uas ua lub luag haujlwm tseem ceeb hauv kev tiv thaiv kab mob loj hauv feem ntau tom qab tsawg kawg ib koob tshuaj tiv thaiv, nyob ntawm seb qhov kev kuaj mob yav dhau los [1, 32, 33] ib.

Kev tsim tshuaj tiv thaiv siv ntau yam kev hloov pauv cov protein, uas suav nrog cov tshuaj tiv thaiv tsis muaj zog ua ke nrog cov khoom siv ntxiv (piv txwv li, polio), cov tshuaj tiv thaiv muaj sia nyob (xws li, MMR), cov protein subunits (fluenza), thiab cov kab mob zoo li cov kab mob (xws li, HPV) [34 ]. Tsis ntev los no, kev nce qib hauv lwm lub platform tau siv cov thev naus laus zis tshiab, suav nrog cov kab mob kis kab mob (xws li VZV thiab Ebola), tshuaj tiv thaiv DNA (nucleic acid) thiab tshuaj tiv thaiv RNA [18,34,35]. Raws li SARS-CoV-2 kev tshawb fawb thiab lwm yam kev tshawb fawb sib piv ntawm HCoV, muaj qib siab ntawm B cell IgG tsim tawm tsam S thiab N proteins, qhia tias ua ntej tus kab mob COVID-19 kis tau lossis txhaj tshuaj tiv thaiv tuaj yeem muab kev tiv thaiv zoo tiv thaiv SARS-CoV-2 re-infection [36–38].

2. Txoj kev

Kev tshuaj xyuas cov ntawv txheeb xyuas cov phooj ywg thiab cov ntawv tshaj tawm uas tau tshaj tawm hauv cov ntaub ntawv hluav taws xob, xws li PubMed, bioxRiv, thiab Google Scholar, tau ua thaum lub Cuaj Hlis 2020 thiab Lub Kaum Hli 2022; Cov kab lus raug xaiv los ntawm cov ntsiab lus hauv qab no: "COVID-19 Tshuaj Tiv Thaiv", "Immune responses after COVID-19", "SARS-CoV-2", "Coronavirus", "Pfizer vaccine", "Vaccine Immunity", "Vaccine efficiency", "Antibody responses", "Memory B cells", "Sinopharm vaccine", "AstraZeneca vaccine", "Vaccine immunogenicity", "Pfizer vaccine immune response", "Oxford-AstraZeneca", " BioNTech/Pfizer", "Sinopharm/BBIBP-CorRV," "effectiveness", "ChAdOx1," "Vaxzevria," "Covishield," "BNT162b1," thiab "BNT162b2".

Cov kab lus raug xaiv thiab tshuaj xyuas los ntawm cov ncauj lus tseem ceeb.

2.1. Factors Involved in SARS-CoV-2 Serological Analysis

Kev tiv thaiv kab mob yog txhais hauv kev tshawb fawb txog kev tiv thaiv kab mob los ntawm kev ntsuas cov tshuaj tiv thaiv kab mob, cov cim ntawm tes, thiab cytokines cuam tshuam rau cov tshuaj tiv thaiv kab mob uas nthuav tawm los ntawm cov kab mob rau kev tiv thaiv kab mob, tshwj xeeb tshaj yog nyob rau hauv cov kab mob tshiab SARSCoV-2. Leukocytes los yog cov qe ntshav dawb, tshwj xeeb tshaj yog B lymphocytes, tsim cov tshuaj tiv thaiv zoo tshaj plaws immunoglobulin G (IgG), uas yuav tau tham ntawm no nyob rau hauv cov ntsiab lus ntawm innate thiab adaptive immune teb [39].

Peb tsab xov xwm tom ntej no yuav nthuav qhia cov ntsiab lus tshwj xeeb hais txog cov cim cellular tshwj xeeb uas tau sau tseg hauv lwm lub cev tiv thaiv kab mob, suav nrog monocytes, dendritic hlwb, thiab lwm yam. B hlwb muaj ntau yam kev ua haujlwm hauv pathologies, suav nrog kev kis kab mob, tso tawm cytokine, ua cov tshuaj tiv thaiv kab mob, kev nthuav qhia, thiab tshuaj tiv thaiv kab mob. Serum IgG feem ntau yog elicited thaum lub ntuj kis kab mob los yog txhaj tshuaj tiv thaiv kab mob cov lus teb thiab yuav ntsuas nyob rau hauv lub ntiaj teb no qhov chaw ntawm lub enzyme-txuas immunosorbent tsom xam (ELISA) thiab lwm yam tshuaj tiv thaiv sub-types (IgG, IgA, IgD, IgM, IgE).

Cov ntaub ntawv tshawb fawb tam sim no feem ntau yog B hlwb uas tsim cov IgG hauv cov lus teb rau SARS-CoV-2, uas yog cov protein uas yooj yim tshaj plaws thiab ruaj khov siv hauv cov kev ntsuas no; cov protein no ces validated raws li tshwj xeeb tiv thaiv kab mob antigens xws li S protein. Txawm li cas los xij, cov tshuaj reagents siv los ntsuas cov tshuaj tiv thaiv-SARS-CoV-2 qhov tshwj xeeb tau txais kev lees paub ntxiv rau qhov tshwj xeeb thiab rhiab heev. Yog li ntawd, lwm cov kev tshawb fawb (n=87) quantify assay rhiab heev ntawm IgA, IgM, thiab IgG nyob rau hauv ratios ntawm 98.6 feem pua ​​: 96.8 feem pua ​​: 96.8 feem pua ​​​​, feem, nrog tshwj xeeb ntawm 98.1 feem pua ​​, 92.3 feem pua ​​, thiab [99.8 feem pua. 40]-qhia cov qauv tam sim no ntawm cov kev ntsuam xyuas thoob plaws cov tuam txhab [41]. Txawm li cas los xij, hauv lwm cov kab mob ua pa, piv txwv li, mob npaws, cov tshuaj tiv thaiv kab mob hauv cov kab mob ua pa sab saud yog ua los ntawm IgA, uas muaj cov kua dej thiab cov khoom zais cia. IgA kuj tau tsim nyob rau hauv cov ntaub so ntswg mucosa-associated lymphoid (MALT), feem ntau nyob rau hauv lamina propria, thiab ces nquag thauj mus rau mucosal nto los ntawm kev cuam tshuam nrog cov polymeric immunoglobulin receptor [42].

For SARS-CoV-2, it is suggested by La Salle et al. tias lwm cov tshuaj tiv thaiv kab mob sib kis tau tshwm sim hauv cov neeg mob COVID-19 cov neeg mob ua lub luag haujlwm tseem ceeb, nrog rau kev qhia txog qib siab ntawm IgM, IgG1, IgA1, IgG2, thiab IgG3 cov tshuaj tiv thaiv thoob plaws hauv kev kis kab mob uas xav tau kev tshawb fawb ntxiv. Tam sim no nws tau xav tias IgG1 thiab IgG3 cuam tshuam nrog SARS-CoV-2 qhov hnyav [43]. IgG2 tuaj yeem tseem ceeb dua hauv cov kab mob teb rau capsular polysaccharide antigens [44]. Cov ntaub ntawv txwv tam sim no muaj los qhia tias yog vim li cas SARS-CoV-2 ua kom pom tseeb xws li cov tshuaj tiv thaiv kab mob tshiab hauv cov kab mob ntev txog IgG1/IgA1 cov lus teb [45]. Txawm li cas los xij, ua ntej xyoo no, Kober et al. tau ua ib qho kev soj ntsuam qhia tias IgG3 thiab IgM tuaj yeem ua lub luag haujlwm rau 80 feem pua ​​​​ntawm tag nrho qhov nruab nrab ntawm SARS-CoV-2, nrog cov lus qhia tias glycosylation xwm txheej ntawm IgG3 cuam tshuam rau SARS-CoV-2 khi tshwj xeeb rau Cov protein [46] Ntawm no, peb yuav muab piv rau tag nrho cov pej xeem cov tshuaj tiv thaiv kab mob cov lus teb tau pom hauv kev tshawb fawb pej xeem.

2.2. Pfizer/BioNTech BNT162b2 COVID-19 Cov tshuaj tiv thaiv kab mob teb

Pfizer thiab Moderna yog cov piv txwv ntawm cov tshuaj tiv thaiv mRNA. Cov no ua los ntawm kev txhaj tshuaj RNA ib ntus coding rau cov hloov kho antigen S protein kom tshem tawm lub cev tiv thaiv kab mob [18]. Cov tshuaj tiv thaiv mRNA siv lipid nanoparticle (LNP) thev naus laus zis tsim los ntawm Canadian Acuitas Therapeutics Inc, thiab tom qab ntawd Pfizer thiab BioNTech tau siv cov thev naus laus zis no hauv kev tsim cov tshuaj tiv thaiv mRNA BNT162b1 thiab BNT162b2 uas tom qab tau xaiv los ua tshuaj tiv thaiv [47]. Cov tshuaj tiv thaiv mRNA encode qhov hloov kho spike protein stabilized nyob rau hauv prefusion conformation, cia lub cev tiv thaiv kab mob los teb rau tus kab mob nyob rau hauv lub prefusion ua ntej SARS-CoV-2 cell nkag. Cov tshuaj tiv thaiv mRNA tau pib pom tias muaj txiaj ntsig zoo thiab tau txais kev soj ntsuam kev nyab xeeb, nce qib los ntawm kev sim tshuaj thiab tau txais kev pom zoo thawj zaug raws li kev pom zoo siv xwm txheej ceev (EUA) daim ntawv tso cai siv rau ntau lub tebchaws [25].

Kev tshawb fawb theem 1/2 pib ntsuas RBD-binding IgG concentrations thiab SARS-CoV-2-neutralizing titers in sera (n=45) [48]. IgG cov tshuaj tiv thaiv tau pom tias nce nrog koob tshuaj, thiab kev khi rau RBD ntawm cov protein S1 tau pom tias raug ntxias [49]. Hauv theem 3 kev sim tshuaj, cov tshuaj tiv thaiv mRNA tau pom tias muaj 95 feem pua ​​​​ntawm kev ua tau zoo [50]. Tom qab pom zoo thaum Lub Kaum Ob Hlis 2020, Pfizer thiab BioNTech pib faib BNT162b2 thoob plaws ntiaj teb [51]. Tom qab ntawd, kev tshawb fawb ntawm cov neeg tau txais kev txhaj tshuaj tiag tiag hauv ntiaj teb tau pib nrhiav cov pab pawg loj dua, qhia meej txog cov lus teb tiv thaiv kab mob los ntawm BNT162b2 thiab nco B / T hlwb rau cov kab mob hauv cov tshuaj tiv thaiv kab mob (IgG, IgM, IgA), yog li qhia meej txog qhov Kev ua tau zoo thiab kev tiv thaiv ntawm BNT162b2. SARS-CoV-2 kis ntawm tib neeg feem ntau tshwm sim los ntawm txoj kev ua pa. Yog li ntawd, nws yog ib qho tseem ceeb uas yuav tau soj ntsuam seb IgA puas tseem tsim tau tom qab kis kab mob lossis txhaj tshuaj tiv thaiv, vim nws lub luag haujlwm hauv kev tiv thaiv mucosal [52]. Ib txoj kev tshawb fawb (n=108) pom tias IgA tiv thaiv S protein (S1) thiab receptor-binding domain (RBD) tau tsim nyob rau hauv cov ntshav 1 hli tom qab ib thiab ob koob tshuaj BNT162b2, tab sis qhov no tsis yog ntsuas raws li secretory IgA. nrog cov ntshav IgG thiab IgA txo qis tom qab 6 lub hlis [53].

Interestingly, txoj kev tshawb nrhiav pom tias anti-S IgM nce nrog lub sijhawm hauv 10 feem pua ​​​​ntawm cov neeg koom. Yog li ntawd, lwm cov kev tshawb fawb (n=27) tau txheeb xyuas qhov sib piv ntawm cov ntshav IgA thiab IgG hauv cov neeg tau txais cov tshuaj tiv thaiv tsis zoo. Antibody thiab cytokine cov lus teb tawm tsam S1, RBD, thiab cov lus teb tag nrho-spike protein tau pom tias SARS-CoV-2-cov hlwb tshwj xeeb B tau ua rau muaj kev hloov pauv- ntsuas T cell-evoked cytokine ntau lawm, txhais los ntawm IL{{9} }, IL-4, IL6, IL-10 thiab TNF- cov lus teb, as Well as chemokine (CCL2, CXCL10) ntau lawm [54]. Lwm cov kev tshawb fawb ntxaws (n=12) ua raws BNT162b2 nrog koob thib ob, qhia tias T cell qhia, raws li ntsuas los ntawm pawg ntawm cov cim sib txawv (CD4 ntxiv / CD8 ntxiv) hauv cov neeg koom nrog cov tshuaj tiv thaiv, kuj tsim IFN-, uas yog qhov qhia tau. of humoral and cellular responses against SARS-CoV-2 epitopes [55]. Lwm txoj kev tshawb fawb (n=20) uas tshwj xeeb tshawb fawb txog kev tiv thaiv kab mob thaum ntxov tom qab ib koob tshuaj BNT162b2 taug qab T cell thiab cov tshuaj tiv thaiv kab mob.

Txoj kev tshawb no pom tias, nyob rau hnub 10, 50 feem pua ​​(10/20), 85 feem pua ​​(17/20), thiab 80 feem pua ​​(16/20) ntawm cov lus teb tau cim 4 × nce, raws li ntsuas los ntawm fluorescence hauv IgM, IgA , thiab IgG. Qhov zoo siab, hauv txoj kev tshawb no, nws tau lees paub tias 20 feem pua ​​(4/20) ntawm cov neeg koom tau ntsuas tau IgG anti-S uas tau thaiv tag nrho ACE2 receptor thiab, raws li ntsuas los ntawm kev ntsuas tus kab mob tsis zoo, tsuas yog 15 feem pua ​​(3/20) ntawm cov neeg koom nrog nAbs, tawm tswv yim tias cov nAbs no yuav tsis tsim nyog rau kev tiv thaiv ntxov. Yog li ntawd, lwm cov kev tshawb fawb sib raug zoo (n=163) tau qhia meej tias cov neeg kis tus kab mob tsis zoo thiab ib txwm muaj cov kab mob tshwm sim ntau dua ntawm IgG cov lus teb 12 hnub tom qab ib koob tshuaj BNT162b2 [56]. Kev tshawb fawb dav dav (n=871) ntawm cov neeg koom nrog uas tau txais ob koob tshuaj BNT162b2 kom suav tag nrho cov lus teb ntawm IgG anti-S protein (uas tau soj ntsuam hauv cov qauv ntshav hauv cov ntsiab lus sib txawv rau 3 lub hlis) kom paub meej tias IgG anti-S protein theem tsis tu ncua nce ntxiv yam tsis muaj kev hloov pauv hauv qib ntawm kev tiv thaiv SARS-CoV-2 S cov lus teb ntawm poj niam txiv neej. Txawm li cas los xij, IgG tau nce siab tom qab koob thib ob ntawm cov tshuaj tiv thaiv BNT162b2, tab sis qhov txo qis tseem ceeb tshwm sim ntawm 3 lub hlis hauv cov neeg laus cov neeg koom nrog [57]. Qhov kev poob qis ntawm 3 lub hlis concurs nrog rau lwm yam kev tshawb fawb zoo sib xws [58].

Yog li ntawd, kev tshawb fawb tau ua los ntsuas qhov IgG anti-S protein teb 6 lub hlis tom qab BNT162b2 thiab pom tias IgG, uas ua rau cov lus teb rau BNT162b2, pib poob qis tom qab lub hlis thib ob ntawm kev txhaj tshuaj [59]. IgG anti-S protein tau raug ntsuas kom pom qhov siab tshaj plaws IgG cov lus teb tshwm sim ntawm 2 lub hlis thiab txo qis rau 4 lub hlis tom ntej, nrog rau qhov nruab nrab 6.3 feem pua ​​​​peak titer tshuav ntawm 6 lub hlis. Cov kev sib txawv tseem ceeb no tshwm sim hauv cov neeg koom ntawm txhua lub hnub nyoog [60,61]. Ib qho kev tshawb fawb (n=92) tau soj ntsuam IgG anti-S protein 7 lub hlis tom qab koob thib ob ntawm BNT162b2, pom tias IgG titers raug txo los ntawm 92 feem pua ​​​​hauv cov pab pawg uas tau lees paub ua ntej SARS-CoV-2 kab mob thiab cov uas tsis tau. IgG titers tseem pom tau thoob plaws hauv lub sijhawm kawm [62].

Txij li thaum BNT162b2 muaj RNA ib ntus coding tsuas yog rau cov protein ntau ntawm tus kab mob SARS-CoV-2, qhov no ua rau muaj peev xwm ua rau lwm cov proteins tuaj yeem raug tshem tawm los ntawm BNT162b2 COVID-19 txhaj tshuaj tiv thaiv. Y. Yoshimura et al. Muab piv rau IgG anti-N thiab anti-S hauv cov tib neeg uas tau txhaj tshuaj nrog ob koob tshuaj BNT162b2, pom tias IgG anti-S protein tsim, thaum lub anti-N protein IgG tiv thaiv N (nucleocapsid) protein tsis [63]. Qhov no ua rau muaj kev nkag siab tias mRNA-raws li COVID{15}} cov tshuaj tiv thaiv kab mob tshwj xeeb rau cov protein ntau ntawm tus kab mob SARS-CoV-2. Ntxiv nrog rau cov tshuaj tiv thaiv-S thiab tiv thaiv-N IgG, lwm txoj kev tshawb fawb tau txheeb xyuas tus neeg mob SARSCoV-2 cov tshuaj tiv thaiv kab mob tiv thaiv kab mob anti-RBD, anti-S1, thiab anti-S2 proteins, pom tias BNT162b2 induces tsim cov tshuaj tiv thaiv tawm tsam tag nrho. S antigens hauv ob lub lis piam, thaum koob thib ob ua rau cov tshuaj tiv thaiv kab mob siab tshaj plaws hauv txhua tus neeg koom, tshwj tsis yog cov tshuaj tiv thaiv N uas tseem tsis zoo ua ntej thiab tom qab txhaj tshuaj [64].

Ntau cov kev tshawb fawb qhia txog kev sib raug zoo ntawm cov tshuaj tiv thaiv nrog qhov pib nce thiab txo qis hauv IgG tom qab qee lub sijhawm tom qab ib lossis ob koob tshuaj BNT162b2 [65]. Yog li ntawd, ib koob thib peb ntawm BNT162b2 tam sim no tau ua tiav, uas kuj tau ua kom pom qhov ua tau zoo ntawm 95.3 feem pua ​​​​ntawm kev tiv thaiv SARS-CoV-2 kab mob hauv theem 3 kev sim tshuaj [66]. Cov ntaub ntawv pov thawj qhia tau tias muaj kev poob qis hauv qhov tshwm sim ntawm kev cog lus SARS-CoV-2 tom qab txhaj tshuaj [67]. Hauv kev tshawb fawb dav dav (n=550,232), cov pov thawj no tau qhia tias muaj kev pheej hmoo ntawm 0.1428 ntawm 65 hnub lossis ib qho 86 feem pua ​​​​kev pheej hmoo txo ​​qis tom qab koob thib ob lossis thib peb.

Yog li ntawd, kev tshawb fawb tsis ntev los no tau qhia meej tias, ua ntej thawj koob tshuaj BNT162b2 tau muab, cov neeg koom nrog cov kab mob ua ntej twb tau muaj cov tshuaj tiv thaiv kab mob IgG anti-S protein, thiab tom qab thawj koob tshuaj, cov tshuaj tiv thaiv kab mob no siab dua li cov neeg koom nrog uas tsis muaj tus kab mob. . Qhov kev tshawb pom no tau xav tias, nrog rau kev txhaj tshuaj tiv thaiv kab mob ua rau muaj kev txhawb nqa ntawm kev tiv thaiv ib txwm muaj.

Yog li, cov txiaj ntsig no qhia txog qhov muaj peev xwm ncua sijhawm txhaj tshuaj thib ob rau cov neeg uas muaj tus kab mob COVID-19 dhau los yuav muaj txiaj ntsig [54,56,68–71]. Hauv kev tshawb fawb tsis ntev los no (n=62), lwm tus kws sau ntawv tau txiav txim siab seb IgG anti-S protein puas tuaj yeem txo qis hauv cov lus teb rau qhov thib ob koob tshuaj BNT162b2 [72]. Ib koob ntawm BNT162b2 tau tshaj tawm tias muaj kev tiv thaiv SARS-CoV-2 rov ua dua tshiab hauv cov neeg mob yav dhau los [73]. BNT162b2 zoo nkaus li ua rau muaj qhov ua rau muaj kev ua siab zoo rau cov lus teb kom muaj nuj nqis hauv cov qauv ntshav, tab sis cov qaub ncaug qis IgG thiab txawm tias qis qis IgA cov tshuaj tiv thaiv. Cov qib ntshav IgA zoo li nce siab tom qab txhaj tshuaj ib zaug thiab tsis nce ntxiv tom qab txhaj tshuaj thib ob [52].

Tsis tas li ntawd, 8 lub hlis tom qab txhaj tshuaj tiv thaiv BNT162b2, cov neeg uas muaj thiab tsis muaj SARS-CoV-2 ua ntej kev kis kab mob tau pom cov qib zoo sib xws ntawm kev nco SARS-CoV-2- tshwj xeeb B cells [54,74]. Yog li ntawd, muab cov kev tshawb fawb saum toj no, nws zoo nkaus li tias cov tshuaj tiv thaiv kab mob S-S protein IgG cov tshuaj tiv thaiv kab mob tiv thaiv kab mob los ntawm 12 hnub, nce siab tom qab 2-3 lub hlis thiab poob ntawm 6 lub hlis hauv sera nrog qis IgM (ib qho cim ntawm kev kis mob ntxov) thiab zoo ib yam li qis qis ntawm secretory IgA hauv ob qho tib si kab mob / tshuaj tiv thaiv cov lus teb. Kev hloov pauv hauv S protein epitopes, suav nrog E484K thiab K417T/N, tau ua rau muaj kev sib kis ntau ntxiv; Yog li ntawd, cellular B cell teb tau soj ntsuam los ntawm kev ntsuas ntxiv B cell cim (CD21, CD27, CD71) los txiav txim qhov ua kom cov CD27 ntxiv rau CD38 ntxiv, CD71 ntxiv rau phenotypes [74]. D. Mileto et al. soj ntsuam cov lus teb los tiv thaiv S IgG ib hlis tom qab koob thib ob ntawm cov tshuaj tiv thaiv Alpha, Gamma, thiab Eta variants.

Lawv pom, hauv kev tshuaj ntsuam xyuas tsis zoo, tias cov lus teb los tiv thaiv S IgG tiv thaiv SARS-CoV-2, nrog cov epitopes tam sim no nyob rau hauv Beta thiab Delta hom kab mob uas ua rau pom kev tiv thaiv ib nrab ntawm kev tiv thaiv kab mob [75]. Lwm qhov kev siv cov kev tshuaj ntsuam transcriptomic tau txiav txim siab tias ib koob ntawm BNT162b2 elicited rov qab cov lus teb ntawm IgA plasmablasts tsom rau S2 protein subunit, nrog IgG plasmablasts nthuav dav rau lub hom phiaj S1 RBD los ntawm naive B cell pool [76]. Cov lus teb no tau txhawb zog los ntawm koob thib ob thiab xa nAbs tawm tsam SARS-CoV-2, concurring that the original Wuhan-Hu-1 variant evoked a stronger immune response of IgG anti-S SARS-CoV{{ 15}} ib. Txawm li cas los xij, qhov kev tiv thaiv kev tiv thaiv kab mob no ntawm SARS-CoV-2 variants tuaj yeem tiv thaiv los ntawm ob koob ntawm BNT162b2, txhawb kev tsim cov hlwb B thiab RBD-cov tshuaj tiv thaiv tshwj xeeb txhawm rau tshem tawm SARS-CoV-2 variants [ 76] ib.

Cov pov thawj tsis ntev los no tau qhia tias Alpha thiab Delta variants tsis muaj peev xwm khiav tawm nAbs, piv rau Beta thiab Omicron variants [77]. Yog li ntawd, B cell txoj kev loj hlob, kev tsim cov tshuaj tiv thaiv kab mob, thiab cov kab mob tom ntej tuaj yeem tsim cov tshuaj tiv thaiv kab mob los ntawm kev tsim cov tshuaj tiv thaiv S protein RBD antigen-specific B hlwb. Tseeb tiag, ib qho tseem ceeb ntawm cov tshuaj tiv thaiv zoo yog tib neeg lub cim xeeb B cell compartment [78]. Raws li tau tham ua ntej, tom qab BNT162b2, lub cim xeeb B hlwb raug tsim thiab tsim cov tshuaj tiv thaiv sib npaug rau cov uas tsav cov lus teb thawj zaug [55]. Nco B hlwb tsim IgA, IgM, thiab IgG isotypes, uas tau pom tias tiv thaiv cov teebmeem ntawm cov ntshav qab zib ntuj poob [53,74]. Lwm qhov kev tshawb nrhiav ntev ntev tau pom tias kev nco B hlwb tseem nyob, txawm hais tias pom tseeb cov tshuaj tiv thaiv txo rau rau lub hlis tom qab BNT162b2 tau muab kev tiv thaiv mus ntev [78–80].

Nyob rau hauv txoj kev tshawb no, Ciabattini li al., (n=145) piv rau cov chav kawm-hloov pauv thiab nco cell cim, raws li ntsuas nyob rau hauv B cell plasmablasts, los txiav txim siab spike protein tshwj xeeb thiab chav kawm-hloov tiv thaiv kab mob rov qab cov lus teb rau spike antigens. Lawv ntsuas sub-sets ntawm B cells (CD19 plus) los ntsuas qhov qhia ntawm CD19 plus , CD24 plus , CD27 plus , and CD38 plus -specific SARS-CoV-2 B cells. Qhov kev tshawb nrhiav tseem ceeb no tau pom tias cov B hlwb no tau tsim cov lus teb feem ntau IgG1 thiab IgG3 thiab tsis muaj IgG2 thiab IgG4 thiab tias qhov kev rov qab nco txog lub cev tiv thaiv kab mob no tau tshwm sim nrog kev nce ntxiv hauv cov protein tshwj xeeb B-cell ua IgG thiab ruaj khov IgA-ua. B hlwb, txog li 6 lub hlis-nrog IgG lub cim xeeb B hlwb ntsuas ntawm 66 feem pua, tab sis kuj tseem muaj IgM cov B hlwb ntawm 100 feem pua ​​​​hauv vitro [78].

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