Kev nyab xeeb thiab kev tiv thaiv kab mob ntawm ib qho AS03-adjuvanted SARS-CoV-2 Recombinant Protein Vaccine (CoV2 PreS DTM) hauv Cov Neeg Laus Noj Qab Haus Huv: Kev Tshawb Nrhiav Ib Ntus Los Ntawm Phase 2, Randomised, Dose-finding, Multicentre Study

Hu rau:joanna.jia@wecistanche.com/ WhatsApp: 008618081934791

Cov ntsiab lus

Keeb kwm

Peb soj ntsuam pebSARS-CoV-2prefusion spike recombinant protein vaccine (CoV2 preS dTM) nrog rau qhov sib txawv adjuvants, unadjuvanted, thiab nyob rau hauv ib lub sij hawm txhaj tshuaj ib zaug thiab ob-txhaj tshuaj nyob rau hauv ib tug yav dhau los theem 1-2 txoj kev tshawb no. Raws li cov txiaj ntsig ib ntus los ntawm txoj kev tshawb no, peb tau xaiv ob lub sijhawm txhaj tshuaj thiab AS03 adjuvant rau kev txhim kho kev kho mob ntxiv. Txawm li cas los xij, qis dua qhov xav tau cov tshuaj tiv thaiv kab mob, tshwj xeeb tshaj yog nyob rau hauv cov neeg laus, thiab siab dua li qhov xav tau reactogenicity tom qab txhaj tshuaj tiv thaiv zaum ob. Hauv txoj kev tshawb fawb tam sim no, peb tau soj ntsuam kev nyab xeeb thiab kev tiv thaiv kab mob ntawm kev ua kom zoo tshaj plaws ntawm CoV2 preS dTM adjuvanted nrog AS03 los qhia txog kev nce mus rau theem 3 kev sim tshuaj.

Cistanche kev paubntawmtiv thaiv kab mob

Cov txheej txheem

Qhov no theem 2, randomized, parallel-pab pawg, kev tshawb fawb ntau npaum li cas tau ua rau cov neeg laus (Ntau dua lossis sib npaug li 18 xyoo), suav nrog cov neeg mob uas twb muaj lawm, cov neeg uas muaj kev tiv thaiv kab mob (tshwj tsis yog cov neeg uas muaj kev hloov pauv hauv nruab nrog cev tsis ntev los no. los yog kws khomob), thiab cov uas muaj feem yuav muaj kev pheej hmoo lojCOVID-19, ntawm 20 lub chaw tshawb fawb soj ntsuam hauv Tebchaws Meskas thiab Honduras. Cov poj niam cev xeeb tub los yog lactating los yog, rau cov uas muaj peev xwm xeeb tub, tsis siv txoj kev zoo ntawm kev tiv thaiv kab mob los yog abstinence, thiab cov uas tau txais cov tshuaj tiv thaiv COVID-19, raug cais tawm. Cov neeg koom nrog tau raug muab tso ua ke (1: 1: 1) siv cov txheej txheem kev sib tham sib tham, nrog rau kev sib cais los ntawm hnub nyoog (18-59 xyoo thiab Ntau dua lossis sib npaug rau 60 xyoo), qhov kev xeem serodiagnostic sai (zoo lossis tsis zoo), thiab siab- muaj kev pheej hmoo kho mob (yog los yog tsis), kom tau txais ob koob tshuaj (hnub 1 thiab hnub 22) ntawm 5 µg (tsawg koob), 10 µg (medium dose), lossis 15 µg (siab koob tshuaj) CoV2 preS dTM antigen nrog cov ntsiab lus AS03 ruaj khov . Tag nrho cov neeg koom thiab cov neeg soj ntsuam cov txiaj ntsig tau raug npog rau kev ua haujlwm pab pawg; Cov neeg ua haujlwm tshawb fawb uas tsis tau npog ntsej muag koom nrog hauv kev npaj tshuaj tiv thaiv tsis koom nrog kev ntsuas kev nyab xeeb. Tag nrho cov neeg ua haujlwm hauv chaw kuaj mob ua qhov kev ntsuam xyuas tau npog ntsej muag rau kev kho mob. Lub hom phiaj tseem ceeb ntawm kev nyab xeeb yog piav qhia txog kev nyab xeeb ntawm txhua tus neeg koom nrog, rau txhua tus neeg sib tw tsim tshuaj tiv thaiv. Cov ntsiab lus ntawm kev nyab xeeb tau raug soj ntsuam rau txhua tus neeg koom nrog uas tau txais tsawg kawg ib koob tshuaj tiv thaiv kev kawm (kev tshuaj xyuas kev nyab xeeb), thiab tau nthuav tawm ntawm no rau lub sijhawm kawm ib ntus (txog hnub 43). Lub hom phiaj tseem ceeb ntawm kev tiv thaiv kab mob yog los piav txog cov tshuaj tiv thaiv kab mob nruab nrab rau D614G variant 14 hnub tom qab txhaj tshuaj thib ob (hnub 36) hauv cov neeg koom nrog.SARS-CoV-2naive leej twg tau txais ob qho tshuaj txhaj, muab cov qauv rau hnub 1 thiab hnub 36, tsis muaj cov txheej txheem sib txawv, thiab tsis tau txais daim ntawv tso cai COVID-19 tshuaj tiv thaiv ua ntej hnub 36. Cov tshuaj tiv thaiv kab mob tsis zoo raug ntsuas los ntawm kev soj ntsuam pseudovirus neutralization thiab nthuav tawm ntawm no mus txog 14 hnub tom qab koob thib ob. Raws li lub hom phiaj thib ob immunogenicity, peb tau soj ntsuam cov tshuaj tiv thaiv kab mob hauv cov neeg tsis yog haiv neeg. Qhov kev sim no tau sau npe nrog ClinicalTrials.gov (NCT04762680) thiab raug kaw rau cov neeg tuaj koom tshiab rau pawg pab pawg qhia ntawm no.

Kev tshawb pom

Ntawm 722 tus neeg koom nrog rau npe thiab muab tso rau thaum Lub Ob Hlis 24, 2021, thiab Lub Peb Hlis 8, 2021, 721 tau txais tsawg kawg ib qho kev txhaj tshuaj (tsawg koob=240, koob tshuaj nruab nrab=239, thiab koob tshuaj siab =242 ). Qhov feem pua ​​​​ntawm cov neeg koom qhia tsawg kawg yog ib qho kev tawm tsam tsis zoo (qhov chaw txhaj tshuaj lossis qhov systemic) hauv thawj 7 hnub tom qab txhaj tshuaj tiv thaiv zoo ib yam ntawm cov pab pawg kho mob (217 [91 feem pua] ntawm 238 hauv pawg tshuaj tsawg, 213 [90 feem pua] ntawm 237 hauv pawg koob tshuaj nruab nrab, thiab 218 [91 feem pua] ntawm 239 hauv pawg koob tshuaj siab); Cov kev cuam tshuam tsis zoo no tau hloov pauv, feem ntau me me mus rau nruab nrab ntawm kev siv zog, thiab tshwm sim ntawm ntau zaus thiab siv zog tom qab txhaj tshuaj thib ob. Plaub tus neeg koom tau tshaj tawm cov xwm txheej tsis txaus siab tam sim ntawd; ob (ib qho ntawm ib pab pawg tsawg thiab cov koob tshuaj nruab nrab) tau txiav txim siab los ntawm cov neeg tshawb xyuas los ntawm cov tshuaj tiv thaiv thiab ob (ib qho hauv pawg tshuaj tsawg thiab koob tshuaj siab) tau suav tias tsis cuam tshuam. Tsib tus neeg koom tau tshaj tawm xya qhov tshuaj tiv thaiv txog kev kho mob tau koom nrog cov xwm txheej tsis zoo (ob leeg hauv pab pawg tsawg, ib pawg hauv cov koob tshuaj nruab nrab, thiab plaub hauv pawg koob tshuaj siab). Tsis muaj tshuaj tiv thaiv kab mob tshwm sim loj heev thiab tsis muaj cov xwm txheej tsis zoo uas muaj kev txaus siab tshwj xeeb tau tshaj tawm. Ntawm cov neeg koom naive rauSARS-CoV-2nyob rau hnub 36, 158 (98 feem pua) ntawm 162 nyob rau hauv pawg neeg koob tshuaj tsawg, 166 (99 feem pua) ntawm 168 nyob rau hauv cov pab pawg neeg nruab nrab, thiab 163 (98 feem pua) ntawm 166 nyob rau hauv cov koob tshuaj muaj tsawg kawg yog ib tug ob-fold nce nyob rau hauv neutralizing antibody titers rau D614G variant los ntawm lub hauv paus. Neutralizing antibody geometric txhais tau tias titers (GMTs) ntawm hnub 36 rau cov neeg koom nrog uas tsis paub qab hau yog 2189 (95 feem pua ​​​​CI 1744–2746) rau pawg qis, 2269 (1792–2873) rau pawg nruab nrab koob, thiab 2895 (2294). -3654) rau pab pawg neeg siab. GMT piv (hnub 36: hnub 1) yog 107 (95 feem pua ​​​​CI 85–135) hauv pawg qis, 110 (87–140) hauv pawg nruab nrab koob, thiab 141 (111–179) hauv siab- koob tshuaj pab pawg. Neutralizing antibody titers nyob rau hauv cov neeg laus uas tsis yog haiv neeg 21 hnub tom qab ib qho kev txhaj tshuaj zoo li siab dua titers tom qab ob qho kev txhaj tshuaj rau cov neeg laus uas tsis paub qab hau, nrog GMTs 21 hnub tom qab ib qho kev txhaj tshuaj rau cov neeg koom nrog uas tsis yog haiv neeg yog 3143 (95% CI 836– 11 815) hauv pawg koob tshuaj tsawg, 2338 (593–9226) hauv pawg koob tshuaj nruab nrab, thiab 7069 (1361–{59}}) hauv pawg koob tshuaj siab.

Saranya Sridhar, Arnel Joaquin, Matthew I Bonaparte, Agustin Bueso, Anne-Laure Chabanon, Aiying Chen, Roman M Chicz, David Diemert, Brandon J Essink, Bo Fu, Nicole A Grunenberg, Helene Janosczyk, Michael C Keefer, Doris M Rivera M , Ya Meng, Nelson L Michael, Sonal S Munsiff, Onyema Ogbuagu, Vanessa N Raabe, Randall Severance, Enrique Rivas, Natalya Romanyak, Nadine G Rouphael, Lode Schuerman, Lawrence D Sher, Stephen R Walsh, Judith White, Dalia von Barbier, Guy de Bruyn, Richard Canter, Marie-Helene Grillet, Maryam Keshtkar-Jahromi, Marguerite Koutsoukos, Denise Lopez, Roger Masotti, Sandra Mendoza, Catherine Moreau, Maria Angeles Ceregido, Shelly Ramirez, Ansoyta Said, Fernanda Tavares-DaayS Shi, Tina Tong, John Treanor, Carlos A Diazgranados*, Stephen Savarino*

Sanofi Pasteur, Nyeem Ntawv, UK (S Sridhar DPhil); Charles R Drew University of Medicine thiab Science, Los Angeles, CA, USA (A Joaquin MD); Sanofi Pasteur, Swiftwater, PA, USA (MI Bonaparte Ph.D., A Chen Ph.D., B Fu Ph.D., H Janosczyk MA, Y Meng PhD, N Romanyak PharmD, D von Barbier MS, G de Bruyn MD, R Canter BSc, D Lopez MSc, R Masotti MS, CA Diazgranados MD, S Savarino MD); Demedica, San Pedro Sula, Honduras (A Bueso MD); Sanofi Pasteur, Lyon, Fabkis (AL Chabanon PharmD, MH Grillet MD); Sanofi Pasteur, Cambridge, MA, USA (RM Chicz Ph.D.); George Washington Tsev Kawm Ntawv ntawm Tshuaj thiab Kev Noj Qab Haus Huv Sciences, Washington, DC, USA (D Diemert MD); Meridian Clinical Research, Omaha, NE, USA (BJ Essink MD); Fred Hutchinson Cancer Research Center, Seattle, WA, USA (NA Grunenberg MD, S Ramirez MS); University of Rochester, Tsev Kawm Ntawv Tshuaj thiab Kho Hniav, Rochester, NY, USA (MC Keefer MD, SS Munsiff MD); INVERIME, Tegucigalpa, Honduras (DM Rivera M MD); Walter Reed Army Institute of Research, Silver Spring, MD, USA (NL Michael MD); Yale University School of Medicine, New Haven, CT, USA (O Ogbuagu MD); New York University Grossman School of Medicine, New York, NY, USA (VN Raabe MD); Synexus Clinical Research Limited, Tempe, AZ, USA (R Severance MD); Sanofi Pasteur, Ciudad de México, Mexico (E Rivas MD); Emory University School of Medicine, Atlanta, GA, USA (Prof NG Rouphael MD); GlaxoSmithKline Vaccines, Wavre, Belgium (L Schuerman MD, M Koutsoukos MS, MA Ceregido PhD, F Tavares-Da-Silva MD); Peninsula Research Associates, Rolling Hills Estates, CA, USA (LD Sher MD); Harvard Medical School, Boston, MA, USA (SR Walsh MDCM); Synexus, Orlando, FL, USA (J White MD); National Institute of Health (NIH), Rockville, MD, USA (M Keshtkar-Jahromi MD) Sanofi Pasteur, Bogota, Colombia (S Mendoza BSc); Sanofi Pasteur, Marcy l'Etoile, Fabkis (C Moreau MSc, A Said BSc); TechData Service Company, King of Prussia, PA, USA (J Shi MS); Txhaj Tshuaj Txhais Lus Txhais Lus Tshawb Fawb, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD, USA (T Tong DrPH); Biomedical Advanced Research and Development Authority, Washington, DC, Tebchaws USA (J Treanor MD) Xa ntawv rau: Dr Saranya Sridhar, Sanofi Pasteur, Nyeem RG61PT, UK

cistanche lub cev tsimntawmtiv thaiv kab mob

Txhais lus

Ob qhov kev txhaj tshuaj ntawm CoV2 preS dTM-AS03 pom tau tias muaj kev nyab xeeb thiab reactogenicity, thiab muaj zog tiv thaiv kab mob hauv cov neeg laus.SARS-CoV-2naive thiab tsis naive. Cov txiaj ntsig no txhawb kev nce mus rau theem 3 kev ntsuas ntawm 10 µg antigen koob tshuaj rau thawj zaug txhaj tshuaj tiv thaiv thiab 5 µg antigen koob tshuaj rau kev txhaj tshuaj tiv thaiv kab mob.

Nyiaj txiag

Sanofi Pasteur thiab Biomedical Advanced Research thiab Development Authority

Taw qhia

COVID-19tau ua rau muaj kev mob tshwm sim tsis tau muaj dua thiab kev tuag thoob ntiaj teb thiab txuas ntxiv ua rau lub ntiaj teb kev noj qab haus huv thiab kev lag luam puas tsuaj ntau dua 2 xyoos txij li thaum nws tshwm sim.1,2 Kev siv zog tshwj xeeb hauv kev txhim kho, tsim khoom, thiab kev faib tawm ntawm COVID-19 cov tshuaj tiv thaiv tau ua rau ntau yam tshuaj tiv thaiv. tso cai rau kev siv xwm txheej ceev 3 lossis kev pom zoo tag nrho. Kev siv zog txuas ntxiv los tsim cov tshuaj tiv thaiv tseem tsim nyog los ua kom tau raws li qhov xav tau thoob ntiaj teb, muab cov kev xaiv tshuaj tiv thaiv lwm yam nrog cov txiaj ntsig kev pheej hmoo ua kom zoo rau ntau haiv neeg, thiab muab kev tiv thaiv dav dav rau cov kev hloov tshiab.

Sanofi Pasteur, koom tes nrog GlaxoSmithKline, tsim ib qho kev hloov khoSARS-CoV-2recombinant-protein tshuaj tiv thaiv siv baculovirus kev qhia-vector system los qhia txog kev ruaj khovSARS-CoV-2prefusion spike (S) protein (CoV2 preS dTM).4 Kev siv cov tshuaj tiv thaiv kab mob ntxiv muaj qhov zoo ntawm cov tshuaj tiv thaiv kab mob thiab kev tiv thaiv ntau dua.5 Hauv theem 1-2 txoj kev tshawb fawb, kev nyab xeeb thiab kev tiv thaiv kab mob ntawm CoV2 preS dTM cov tshuaj tiv thaiv. adjuvanted nrog AS03 (CoV2 preS dTM-AS03; GlaxoSmithKline) los yog AF03 (Sanofi Pasteur) ntawm ob koob tshuaj antigen (5 µg rau koob tshuaj qis thiab 15 µg rau cov koob tshuaj siab) tau soj ntsuam hauv cov neeg laus noj qab haus huv hnub nyoog 18 xyoo lossis tshaj saud.4 Ib ntus cov ntaub ntawv los ntawm txoj kev tshawb no tau ua rau kev xaiv ob lub sijhawm txhaj tshuaj thiab AS03 adjuvant rau kev txhim kho kho mob ntxiv. Txawm li cas los xij, cov tshuaj tiv thaiv qis dua li qhov xav tau, tshwj xeeb tshaj yog rau cov neeg laus (Ntau dua lossis sib npaug li 60 xyoo), thiab siab dua qhov xav tau reactogenicity tom qab txhaj tshuaj tiv thaiv zaum ob. Theem 1-2 kev soj ntsuam cov qauv tshuaj ntsuam xyuas tau qis dua li qhov xav tau antigen concentrations (1·3 µg rau cov koob tshuaj qis thiab 2·6 µg rau cov koob tshuaj siab), uas peb xav tias ua rau txo qis cov tshuaj tiv thaiv kab mob. Qhov nce reactogenicity tau xav tias yog tshwm sim los ntawm ntau dua li kev cia siab ntawm cov tswv tsev-cell protein cov ntsiab lus nyob rau hauv cov tshuaj tiv thaiv formulations.4 Nyob rau hauv txoj kev tshawb no, peb tsom mus soj ntsuam kev nyab xeeb, reactogenicity, thiab immunogenicity ntawm peb optimized formulations ntawm CoV2 preS dTM-AS03. .

cistanche amazonntawmtiv thaiv kab mob

Cov txheej txheem

Kawm tsim thiab koom nrog

Qhov no yog ib ntus txuas ntxiv 2, randomized, hloov kho ob qhov muag tsis pom kev, sib luag-pab pawg, kev tshawb fawb ntau npaum li cas, ua tiav hauv 20 lub chaw tshawb fawb soj ntsuam hauv Tebchaws Meskas thiab Honduras, nrog rau lub sijhawm teem sijhawm kwv yees li 13 lub hlis. Ntawm no, peb nthuav tawm cov ntaub ntawv kev nyab xeeb ib ntus thiab cov ntaub ntawv reactogenicity mus txog hnub kawm 43, 3 lub lis piam tom qab txhaj tshuaj thib ob, thiab cov ntaub ntawv tiv thaiv kab mob mus txog rau hnub 36.

Cov neeg laus hnub nyoog 18 xyoo thiab laus dua tau tsim nyog rau kev koom nrog hauv txoj kev tshawb no. Cov poj niam cev xeeb tub los yog lactating los yog, rau cov me nyuam muaj peev xwm, tsis siv txoj kev zoo ntawm kev tiv thaiv kab mob los yog abstinence los ntawm tsawg kawg yog 4 lub lis piam ua ntej thawj koob mus txog rau tsawg kawg yog 12 lub lis piam tom qab koob thib ob, thiab cov neeg uas tau txais tus kab mob COVID{ {3}} tshuaj tiv thaiv, tsis suav nrog. Txhawm rau tso cai rau kev ntsuas kev ua tau zoo ntawm cov tshuaj tiv thaiv hauv pab pawg uas muaj kev pheej hmoo siab, cov tib neeg uas muaj kev kho mob ua ntej, cov neeg uas muaj kev tiv thaiv kab mob (tshwj tsis yog cov uas tau txais cov khoom siv hauv nruab nrog cev lossis cov pob txha pob txha hloov hauv 180 hnub dhau los lossis tshuaj kho mob hauv 90 hnub dhau los) , thiab cov uas muaj peev xwm ua rau muaj kev pheej hmoo ntau ntxiv rau COVID-196 tau txais kev koom tes hauv txoj kev tshawb no. Cov txheej txheem suav nrog thiab tsis suav nrog, thiab cov npe ntawm cov kev mob nkeeg uas suav tias yog cuam tshuam nrog kev pheej hmoo ntawm tus mob coronavirus hnyav ntxiv-19, tau piav qhia tag nrho hauv daim ntawv ntxiv (p 4).

Txoj kev tshawb no tau ua tiav raws li International Conference on Harmonization cov txheej txheem rau Kev Kho Mob Zoo thiab cov hauv paus ntsiab lus ntawm Kev Tshaj Tawm ntawm Helsinki. Cov txheej txheem thiab cov kev hloov kho tau pom zoo los ntawm cov neeg ua haujlwm ywj pheej ntawm kev coj ncaj ncees hauv pawg tswj hwm kev tshuaj xyuas thiab cov koom haum tswj hwm, raws li cov cai hauv zos. Kev sau ntawv pom zoo tau txais los ntawm cov neeg koom ua ntej cov txheej txheem kawm tiav.

Randomization thiab daim npog qhov ncauj

Ib daim ntawv teev npe randomization tau tsim los ntawm ib pab pawg neeg ywj pheej nrog kev npaj randomization thiab ib qho kev sib tham sib tham hauv tshuab ua ntej pib kev tso npe. Qhov randomization muaj peb yam stratification, suav nrog pawg hnub nyoog (18–59 xyoo thiab Ntau dua lossis sib npaug li 60 xyoo), lub hauv paus kab mob SARS-CoV-2 ceev serodiagnostic test positivity (zoo lossis tsis zoo los ntawm COVID-19 immunoglobulin [Ig]G thiab IgM Rapid Test Cassette; Healgen Scientific, Houston, TX, TEB CHAWS USA), thiab muaj kev pheej hmoo siab kho mob (yog lossis tsis yog). Nyob rau hauv txhua lub stratum, cov neeg tuaj koom tau muab tso rau hauv qhov sib piv 1: 1: 1, nrog rau qhov loj me ntawm rau, kom tau txais ob txoj kev txhaj tshuaj (hnub 1 thiab hnub 22) ntawm 5 ug (tsawg koob), 10 ug (nruab nrab koob) , los yog 15 ug (siab koob tshuaj) ntawm CoV2 preS dTM antigen, nrog rau cov koob tshuaj tas li ntawm AS03 adjuvant. Ib pawg ntawm cov neeg koom nrog uas tau kuaj qhov tsis zoo nrog SARS-CoV-2 kev kuaj serodiagnostic sai tau ntxiv rau cov hnub nyoog thiab pab pawg kawm thiab tau muab cov qauv rau kev soj ntsuam ntawm cov cell-mediated immunity thiab mucosal antibodies.

Tag nrho cov neeg koom thiab cov neeg soj ntsuam cov txiaj ntsig tau raug npog rau kev ua haujlwm pab pawg; Cov neeg ua haujlwm tshawb fawb uas tsis tau npog ntsej muag koom nrog hauv kev npaj tshuaj tiv thaiv tsis koom nrog kev ntsuas kev nyab xeeb. Tsis tas li ntawd, tag nrho cov neeg ua haujlwm hauv chaw kuaj mob ua cov tshuaj ntsuam xyuas rau txoj kev tshawb no tau npog lub luag haujlwm rau kev kho mob.

Cov txheej txheem

Cov recombinant protein antigen CoV2 preS dTM yog tsim los siv Sanofi Pasteur proprietary kab-cell baculovirus kev qhia vector system, raws li S-protein sequence los ntawm Wuhan-Hu -1 (D614) siv hom, raws li tau piav qhia yav dhau los .4 Lub AS03 adjuvant system (GlaxoSmithKline Vaccines, Rixensart, Belgium) yog cov roj-hauv-dej emulsion uas muaj 11·86 mg tocopherol thiab 10·69 mg squalene per 0·5 mL tshuaj tiv thaiv dose.4,7 CoV2 preS dTM-AS03 cov tshuaj tiv thaiv cov qauv tau nthuav tawm hauv ob lub vials cais, ib lub vial multidose uas muaj AS03 (tsawg rau kaum koob) thiab ib koob tshuaj ib zaug uas muaj ib qho ntawm peb cov tshuaj tiv thaiv antigen. Ib qho sib npaug ntawm cov emulsion adjuvant tau ntxiv rau lub vial uas muaj cov antigen thiab sib xyaw ua ntej txhaj tshuaj. Kev txhaj tshuaj tiv thaiv (0·5 mL ib koob tshuaj) tau tswj hwm los ntawm cov neeg ua haujlwm tsim nyog thiab tau txais kev cob qhia los ntawm kev txhaj tshuaj intramuscular mus rau thaj tsam deltoid ntawm sab caj npab.

Cov ntshav kuaj thiab cov nasopharyngeal swabs tau sau ua ntej txhua qhov tshuaj tiv thaiv txhawm rau txheeb xyuas seb cov neeg koom nrog yav dhau los lossis tam sim no SARS-CoV-2 kab mob (tsis paub lossis tsis paub). Cov neeg koom nrog raug cais raws li neeg tsis paub qab hau lossis tsis yog haiv neeg nyob rau hnub 1 thiab hnub 22 lossis hnub 1 lossis hnub 22 los ntawm kev soj ntsuam cov qauv ntshav siv Eecsys electrochemiluminescence immunoassays txhawm rau kuaj pom cov tshuaj tiv thaiv S (Elecsys Anti-SARS-CoV-2 S assay; Roche, Indianapolis, IN, USA) ntawm kev kawm hnub 1 thiab rau kev kuaj pom cov tshuaj tiv thaiv nucleocapsid antibodies (Elecsys Anti-SARS-CoV-2 N; Roche) ntawm hnub kawm 1 thiab 22; and detection of SARS-CoV-2 nucleic acids in nasopharyngeal swabs using nucleic-acid amplification tests (NAAT; Abbott RealTime SARS-CoV-2 assay; Abbott Molecular, Des Plaines, IL, USA) nyob rau hnub kawm 1 thiab 22. Kev tshuaj xyuas tau ua tiav raws li cov neeg tsim khoom cov lus qhia. Peb txhais tau tias cov neeg koom nrog ua tsis ncaj rau SARS-CoV-2 ntawm hnub kawm 1 thiab 22 yog tias lawv kuaj tsis zoo rau cov tshuaj tiv thaiv S antibodies rau hnub kawm 1 thiab rau ob qho tib si anti-nucleocapsid cov tshuaj tiv thaiv thiab SARS-CoV-2 nucleic acids nyob rau hnub 1 thiab 22; peb txhais tau tias cov neeg koom tsis yog haiv neeg yog tias lawv tau kuaj pom qhov zoo ntawm tsawg kawg yog ib qho ntawm peb qhov kev xeem nyob rau hnub kawm 1, 22, lossis ob qho tib si (saib ntxiv p 5).

Cov ntshav kuaj yuav raug sau los ntawm cov neeg tuaj koom ntawm txhua qhov kev mus ntsib mus txog hnub 387 rau kev ntsuas kev tiv thaiv kab mob; Kev ntsuam xyuas immunogenicity ntawm hnub 1, hnub 22, thiab hnub 36 tau nthuav tawm ntawm no. SARS-CoV-2 neutralizing-antibody titers tawm tsam D614G variant thiab beta (B.1.351) variant tau ntsuas nrog pseudovirus neutralization assay, siv HIV-1 pseudovirions nthuav qhia qhov ntev S protein ntawm sib txawv, 8 ntawm Monogram Biosciences LabCorp (South San Francisco, CA, USA). pseudovirus neutralization assay tau piav qhia meej hauv daim ntawv ntxiv p 6. Neutralizing antibody titers raug xam raws li qhov sib npaug ntawm cov ntshav dilution uas ua rau 50 feem pua ​​neutralization. Binding antibody profiles raug soj ntsuam los ntawm kev ntsuas SARS-CoV-2 anti-S protein IgG cov tshuaj tiv thaiv nrog kev tsis ncaj ELISA (Nexelis, Laval, Canada), raws li tau piav qhia yav dhau los.4 Tus qauv siv (006/GCN4/Std/01/ 2020) tau npaj los ntawm kev sib sau plaub 5 mL cov qauv ntawm COVID-19 convalescent serum (Quebec, Canada) los ntawm cov neeg mob uas tsis muaj tsos mob tsawg kawg 14 hnub tom qab kis kab mob. Peb tau tsim kev sib koom ua ke hauv EU / mL, raws li qhov ntsuas geometric ntawm ib nrab-qhov siab tshaj plaws concentration (EC50) los ntawm 69 tus qauv siv tau, raws li qhov tsis txaus ntseeg ntawm 1142 EU / mL. Neutralizing antibody thiab binding antibody teb rau D614G tau ntsuas nyob rau hauv tag nrho cov neeg koom rau hnub 1, hnub 22, thiab hnub 36.

Neutralizing antibody teb rau cov beta variant tau ntsuas nyob rau hnub 36. Tag nrho cov ntshav kuaj tau txhawb nqa ex vivo nrog SARS-CoV-2 S antigen (spike-GCN4; Nexelis), siv TruCulture system (Rules-Based Medicine, Austin , TX, USA) raws li tau piav qhia yav dhau los.4 Ib qho microsphere-based multiplex immunoassay (TruCulture OptiMAP assay; Rules-Based Medicine) tau siv los ntsuas qhov tshwj xeeb ntawm interferon (IFN ), qog necrosis factor (TNF ), interleukin (IL){ {9}}, IL-4, IL-5, thiab IL-13 ntawm validated cytokine-profiling panels. Cov paib tshuaj tiv thaiv tau txheeb xyuas ntawm Luminex platform (Luminex Corporation, Austin, Texas, USA), thiab cytokine concentrations tau suav nrog cov software hloov kho (Rules-Based Medicine plate reader version 2.1.5.8; phaj saib version 5.1.1.2) siv tus qauv nkhaus rau kev tsim cytokine tshwj xeeb ntawm txhua lub sijhawm.

Participants were provided a diary card to capture solicited and unsolicited adverse events for up to 21 days after the second injection; serious adverse events (SAEs), adverse events of special interest, and medically attended adverse events are being collected over the duration of the study. Adverse events were graded for intensity (from 1 [no interference with usual activities; ≥25 mm to ≤50 mm for injection site erythema and swelling; or ≥38·0°C to ≤38·4°C for fever] to 3 [severe and prevents usual activities; >100 mm rau txhaj tshuaj erythema thiab o; los yog siab dua lossis sib npaug li 39·0 degree rau kub taub hau]) thiab tau raug soj ntsuam los ntawm tus kws tshawb fawb txog qhov mob hnyav thiab muaj feem cuam tshuam nrog kev tshawb fawb tshuaj tiv thaiv. Phau Ntawv Txhais Lus Kho Mob rau Kev Tswj Xyuas Kev Ua Si (MedDRA) cov kab ke hauv nruab nrog cev thiab cov lus nyiam raug kaw rau cov xwm txheej tsis zoo. Cov xwm txheej tsis zoo uas suav tias yog tshuaj tiv thaiv muaj feem cuam tshuam tau raug sau tseg tias muaj kev cuam tshuam tsis zoo.

Cov txiaj ntsig

Lub hom phiaj tseem ceeb ntawm kev nyab xeeb yog piav qhia txog kev nyab xeeb ntawm txhua tus neeg koom nrog, rau txhua tus neeg sib tw tsim tshuaj tiv thaiv. Hauv qhov kev soj ntsuam ib ntus no, peb piav qhia txog cov ntsiab lus tseem ceeb ntawm kev nyab xeeb mus txog hnub 43 (21 hnub tom qab txhaj tshuaj thib ob), uas suav nrog cov xwm txheej tsis zoo hauv 30 feeb ntawm txhua qhov kev txhaj tshuaj, thov kev txhaj tshuaj rau qhov chaw (mob, erythema, thiab o), thiab thov cov tshuaj tiv thaiv kab mob (ua npaws, mob taub hau, malaise, myalgia, arthralgia, thiab chills) mus txog 7 hnub tom qab txhua qhov kev txhaj tshuaj, cov xwm txheej tsis txaus siab txog li 21 hnub tom qab txhaj tshuaj kawg, thiab kho mob mus koom cov xwm txheej tsis zoo, SAEs, thiab cov xwm txheej tsis zoo ntawm kev txaus siab tshwj xeeb thoob plaws qhov kev kawm. Cov xwm txheej tsis zoo ntawm kev txaus siab tshwj xeeb suav nrog cov tshuaj tiv thaiv anaphylactic, kev ua rau muaj kev cuam tshuam dav dav, thrombocytopenia, thiab muaj peev xwm tiv thaiv kab mob sib kis.9 Lub hom phiaj kev nyab xeeb thib ob (kom nthuav tawm lwm qhov) tau kuaj pom cov tsos mob ntawm COVID-19 thiab serologically lees paub SARS-CoV{{ 11}} kab mob.

Lub hom phiaj tseem ceeb ntawm kev tiv thaiv kab mob yog los piav qhia cov tshuaj tiv thaiv kab mob nruab nrab rau D614G variant 14 hnub tom qab txhaj tshuaj thib ob (hnub 36) hauv cov neeg koom nrog SARS-CoV-2 naive. Lub hom phiaj thib ob ntawm immunogenicity suav nrog kev ntsuam xyuas cov lus teb cov tshuaj tiv thaiv kab mob hauv cov neeg tsis paub lus thiab khi cov tshuaj tiv thaiv kab mob thiab ua rau cov tshuaj tiv thaiv tsis zoo hauv cov neeg koom nrog uas tsis yog neeg tsis paub qab hau. Cov lus teb tshuaj tiv thaiv kab mob tau piav qhia los ntawm lub hauv paus ntawm geometric txhais tau tias titers (GMTs) rau neutralizing antibodies lossis geometric mean concentrations (GMCs) rau khi cov tshuaj tiv thaiv. Peb suav GMT ratios (GMTRs) thiab GMC ratios (GMCRs) rau tom qab txhaj tshuaj tiv thaiv (hnub 36) piv rau prevaccination (hnub 1), feem ntawm cov neeg koom nrog tsawg kawg yog ob zaug lossis plaub-fold nce hauv cov tshuaj tiv thaiv kab mob los ntawm lub hauv paus ntawm txhua lub sijhawm tom qab txhaj tshuaj. , thiab proportions ntawm teb. Ntawm cov neeg koom nrog uas muaj qhov tsis zoo ntawm cov tshuaj tiv thaiv kab mob hauv qab qhov qis qis ntawm kev ntsuas (LLOQ) ntawm qhov pib, cov neeg teb tau txhais tias yog cov neeg uas muaj tsawg kawg yog ob npaug ntawm cov titers tom qab txhaj tshuaj tiv thaiv hnub 1. Hauv cov neeg koom nrog cov hauv paus titers siab dua LLOQ , cov neeg teb yog cov uas muaj tsawg kawg yog plaub npaug ntawm titers tom qab txhaj tshuaj tiv thaiv cov txheeb ze rau hnub 1. Prevaccination titers hauv qab qhov kev ntsuam xyuas LLOQ (1:40) tau muab tus nqi ntawm ib nrab ntawm LLOQ.

Rau cov lus teb ntawm cov tshuaj tiv thaiv kab mob ntawm tes (ib lub hom phiaj tshawb nrhiav), fold nce hauv ib tus neeg cytokines ntawm hnub 36 los ntawm hnub 1 thiab hnub 22 los ntawm hnub 1 tau suav los ntawm kev faib hnub 22 lossis hnub 36 kev ntsuas los ntawm hnub 1 kev ntsuas; qhov sib piv ntawm fold nce rau cytokine khub (piv txwv li, IFN rau IL-4) ​​thiab lawv 95 feem pua ​​​​CIs raug xam. Lwm lub hom phiaj ntawm kev soj ntsuam immunogenicity, yuav tsum tau nthuav tawm rau lwm qhov, suav nrog kev soj ntsuam ntawm qhov sib piv ntawm qhov nruab nrab rau kev khi cov tshuaj tiv thaiv kab mob thiab kev ntsuam xyuas cov tshuaj tiv thaiv mucosal. Peb kuj tau soj ntsuam cov tshuaj tiv thaiv kab mob nruab nrab rau hnub 36 rau cov beta variant raws li lub hom phiaj tshawb nrhiav.

Hauv kev soj ntsuam tom qab hoc, neutralizing antibody thiab binding antibody teb tawm tsam D614G variant tau ntsuas nyob rau hauv ib lub vaj huam sib luag ntawm tib neeg convalescent-serum kuaj (Sanguine Biobank, Waltham, MA, USA; iSpecimen, Lexington, MA, USA; PPD, Wilmington, NC, TEB CHAWS USA; 79 cov qauv) siv tib qhov kev ntsuam xyuas uas tau siv rau ntawm cov neeg koom nrog cov ntshav kuaj ntshav, hauv tib lub chaw kuaj mob, thiab nyob rau hauv ib lub sij hawm ib ntus kom txo qis qhov kev ntsuam xyuas sib txawv raws sij hawm. Convalescent qauv tau txais los ntawm cov neeg pub dawb uas tau rov zoo los ntawm COVID-19 (nrog rau kev kho mob hnyav txij li mob me mus rau qhov hnyav) thiab cov uas tsis muaj tsos mob thaum lub sijhawm sau cov qauv, raws li tau piav qhia dhau los.4 Qhov sib piv ntawm cov tshuaj tiv thaiv kab mob tiv thaiv kab mob titers rau convalescent serum titers raug xam rau txhua pawg antigen-dose, los ntawm pawg hnub nyoog.

Kev txheeb xyuas txheeb cais Tag nrho cov kev ntsuam xyuas npaj tau piav qhia. Ib qho piv txwv loj ntawm 160 cov neeg koom nrog uas tsis paub meej rau SARS-CoV-2 ib pab pawg tau kwv yees kom ua kom muaj qhov tsawg kawg nkaus pom GTR ntawm pawg tshuaj tiv thaiv ntawm 0·73, piv txwv li GMTR tiag ntawm 1 thiab SD ntawm 0·67 (kwv yees rau qhov kev ntsuam xyuas pseudovirus neutralization) nrog 95 feem pua ​​​​qhov yuav tshwm sim. Piv txwv tias tus nqi attrition ntawm 15 feem pua ​​​​thiab capping qhov feem ntawm cov kev kuaj pom zoo los ntawm SARS-CoV-2 ceev serodiagnostic test ntawm 20 feem pua ​​​​ntawm cov neeg kawm, tag nrho cov kev kawm loj ntawm 720 tus neeg koom (240 hauv txhua pab pawg) yog npaj.

Cov ntsiab lus ntawm kev nyab xeeb tau raug soj ntsuam nyob rau hauv qhov kev ntsuam xyuas kev nyab xeeb, uas suav nrog txhua tus neeg koom nrog uas tau txais yam tsawg kawg ib koob tshuaj tiv thaiv kev kawm thiab cov ntaub ntawv raug tshuaj xyuas raws li cov tshuaj tiv thaiv tau txais. Immunogenicity tau raug soj ntsuam nyob rau hauv cov txheej txheem kev tshuaj ntsuam xyuas ib zaug, uas suav nrog cov neeg koom nrog uas tau txais ob qho tshuaj txhaj, muab cov ntshav kuaj rau hnub 1 thiab hnub 36, tsis muaj cov txheej txheem ua ntej sib txawv, thiab tsis tau txais kev tso cai COVID-19 tshuaj tiv thaiv ua ntej hnub 36; cov ntaub ntawv tau raug tshuaj xyuas raws li pawg tshuaj tiv thaiv uas cov neeg koom nrog raug muab tso rau hauv random.

Cov kev ntsuam xyuas tag nrho suav nrog txhua tus neeg koom nrog uas tau txais tsawg kawg ib qho kev txhaj tshuaj. Cell-mediated immunity tau soj ntsuam nyob rau hauv ib qho randomly xaiv subset ntawm ib-protocol tsom xam teeb. Txhawm rau xam qhov feem pua ​​​​ntawm cov neeg koom nrog qhov kawg ntawm qhov kawg, tus naj npawb ntawm cov neeg koom los ntawm kev txheeb xyuas teeb tsa nrog cov ntaub ntawv muaj rau qhov kawg ntawd tau siv los ua tus lej. Kev tshuaj ntsuam xyuas pab pawg ua ntej rau qhov tseem ceeb ntawm kev nyab xeeb yog ua los ntawm pab pawg hnub nyoog (18–59 xyoo thiab Ntau dua lossis sib npaug rau 60 xyoo), lub hauv paus kab mob SARS-CoV-2 naive status (naive at day 1 and non-naive at day 1), thiab muaj kev pheej hmoo siab kho mob (yog lossis tsis yog).

Immunogenicity subgroup ntsuam xyuas tau ua los ntawm pawg hnub nyoog thiab muaj kev pheej hmoo kho mob siab. 95 feem pua ​​​​CIs rau GMTs, GMCs, GMTRs, thiab GMCRs tau suav nrog siv qhov kwv yees li qub ntawm cov log hloov pauv titers. 95 feem pua ​​​​CIs rau qhov kev faib ua feem ntawm cov neeg koom nrog tsawg kawg yog ob zaug lossis plaub zaug nce lossis cov neeg teb tau suav nrog txoj kev Clopper-Pearson.10

95 feem pua ​​​​CIs rau qhov sib txawv ntawm cov neeg koom nrog tsawg kawg yog ob zaug lossis plaub zaug nce ntxiv thiab cov neeg teb tau suav nrog siv Newcombe-Wilson cov qhab nia yam tsis muaj kev kho txuas ntxiv.10 Kev txheeb xyuas txheeb cais tau ua tiav siv SAS version 9.4 lossis tom qab ntawd.

Cov txiaj ntsig

Ntawm 722 tus neeg koom nrog rau npe thiab muab tso rau ib qho ntawm peb pawg kev tshawb fawb thaum Lub Ob Hlis 24, 2021, thiab Lub Peb Hlis 8, 2021, 721 tau txais tsawg kawg ib qho kev txhaj tshuaj (pawg koob tshuaj qis 240, pab pawg koob tshuaj nruab nrab 239, thiab pawg koob tshuaj siab. 242). Tag nrho ntawm 22 tus neeg tuaj koom tsis tau txiav txim siab txoj kev tshawb fawb los ntawm hnub 43, tsis muaj dab tsi vim yog qhov tshwm sim tsis zoo (daim duab 1). Cov neeg koom nrog hauv kev tsom xam kev nyab xeeb yog hnub nyoog 18–95 xyoo (360 hnub nyoog 18–59 xyoo, 361 hnub nyoog Ntau dua lossis sib npaug rau 60 xyoo); Cov yam ntxwv ntawm cov pej xeem hauv paus tau sib npaug ntawm cov pab pawg kho mob (table 1) thiab hnub nyoog strata (appendix pp 7–8). Zuag qhia tag nrho, 437 (61 feem pua) ntawm 721 tus neeg koom muaj tsawg kawg yog ib qho kev mob nkeeg uas muaj kev pheej hmoo siab (tag nrho tsom xam; daim ntawv txuas ntxiv p 9).

Qhov feem pua ​​​​ntawm cov neeg koom qhia tsawg kawg yog ib qho kev tawm tsam tsis zoo (qhov chaw txhaj tshuaj lossis qhov systemic) hauv thawj 7 hnub tom qab txhaj tshuaj tiv thaiv zoo ib yam ntawm cov pab pawg kho mob, rau ib qho kev siv zog (217 [91 feem pua] ntawm 238 hauv cov pab pawg tsawg, 213 [90 feem pua] ntawm 237 nyob rau hauv pab pawg nruab nrab koob, thiab 218 [91 feem pua] ntawm 239 nyob rau hauv pawg high-dose) thiab rau qib 3 siv (52 [22 feem pua] ntawm 238 nyob rau hauv cov low-dose pab pawg, 49 [ 21 feem pua] ntawm 237 nyob rau hauv pawg nruab nrab koob, thiab 45 [19 feem pua] ntawm 239 nyob rau hauv pawg high-dose; appendix pp 10–12). Qhov feem ntau tshaj tawm hais txog kev txhaj tshuaj-qhov tshuaj tiv thaiv yog qhov mob ntawm qhov chaw txhaj tshuaj (daim duab 2A), thiab feem ntau tshaj tawm cov lus qhia txog kev mob tshwm sim yog malaise, mob taub hau, thiab myalgia (daim duab 2B). Qib 3 qhov kev xav tau tshwm sim tsis tu ncua, feem ntau tshwm sim rau hnub ntawm, lossis hnub tom qab, txhaj tshuaj tiv thaiv (appendix pp 28–31) thiab daws tsis pub dhau 2 hnub yam tsis tas yuav kho mob.

Zuag qhia tag nrho, plaub qhov xwm txheej tsis txaus siab tam sim ntawd tau tshaj tawm hauv plaub tus neeg koom nrog (cov ntawv txuas ntxiv pp 10–12): ob qhov kev soj ntsuam los ntawm tus neeg soj ntsuam kom muaj cov tshuaj tiv thaiv (qib 1 lymphadenopathy nyob rau hauv pawg qis thiab qib 1 paraesthesia hauv pawg nruab nrab koob. , nyob rau tib sab ntawm qhov chaw txhaj tshuaj) thiab ob qho tib si tsis cuam tshuam (qib 1 presyncope hauv pawg qis thiab qib 3 mob ntshav siab hauv pawg neeg siab). Cov ntaub ntawv ntawm lymphadenopathy daws nrog tshuaj tsis pub dhau 5 hnub, thaum lwm cov xwm txheej tsis zoo daws tau tshwm sim hauv 1 hnub.

Qhov feem pua ​​​​ntawm cov neeg koom qhia tsawg kawg yog ib qho kev tshwm sim tsis zoo (lossis cov tshuaj tiv thaiv tsis zoo) txog li 21 hnub tom qab txhaj tshuaj tiv thaiv zoo ib yam ntawm cov tshuaj antigen (cov ntawv txuas ntxiv pp 10–12). Qib 3 cov xwm txheej tsis txaus siab tau tshaj tawm ntau zaus hauv pawg koob tshuaj siab (19 [8 feem pua] ntawm 241 vs tsib [2 feem pua] ntawm 240 hauv pawg koob tshuaj qis thiab rau [3 feem pua] ntawm 240 hauv cov koob tshuaj nruab nrab pab pawg), raws li qib 3 cov kev tsis txaus siab tsis txaus siab (ib qho [<1%] of="" 240="" in="" the="" low-dose="" group,="" three="" [1%]="" of="" 240="" in="" the="" medium-dose="" group,="" and="" five="" [2%]="" of="" 241="" in="" the="" high-dose="" group).="" unsolicited="" adverse="" events="" and="" adverse="" reactions="" tended="" to="" be="" reported="" more="" frequently="" among="" younger="" adults="" than="" older="" adults="" in="" the="" low-dose="" and="" medium-dose="" groups,="" but="" not="" in="" the="" high-dose="" group="" (appendix="" pp="" 10–12).="" the="" majority="" of="" unsolicited="" adverse="" reactions="" were="" compatible="" with="" reactogenicity="" symptoms="" (appendix="" p="" 13),="" were="" of="" grade="" 1="" or="" 2="" intensity,="" occurred="" within="" the="" first="" 4="" days="" after="" injection,="" and="" generally="" resolved="" within="" 7="">

Rau tus neeg koom nrog hauv pawg neeg koob tshuaj ntau thiab ib tus hauv pawg neeg tsawg tau tshaj tawm cov xwm txheej tsis zoo nrog MedDRA nyiam cov ntsiab lus ntawm cov ntshav siab, siab systolic ntshav siab, qhov tseem ceeb kub siab, lossis kub siab. Cov xwm txheej tsis zoo no tshwm sim sai tom qab txhaj tshuaj tiv thaiv, kho tus kheej hauv 1-2 hnub, thiab tshwm sim tsis muaj lwm yam tsos mob tshwm sim hauv txhua qhov tab sis ib kis; ib tus neeg koom nrog qib 3 mob ntshav siab muaj qhov ua pob liab liab thiab mob taub hau (txhua qhov kev ntsuam xyuas muaj feem cuam tshuam nrog kev tshawb fawb tshuaj tiv thaiv) thiab kev ntxhov siab (kuaj raws li tsis cuam tshuam). Kev kho mob tau tuaj koom cov xwm txheej tsis zoo tau tshaj tawm hauv 62 (9 feem pua) ntawm 721 tus neeg koom, tsis muaj qhov sib txawv ntawm pawg kho mob (appendix pp 10–12). Ntawm cov no, xya qib 3 cov xwm txheej tsis zoo (qhia los ntawm tsib tus neeg koom) raug soj ntsuam los ntawm tus neeg tshawb xyuas kom muaj feem cuam tshuam nrog cov tshuaj tiv thaiv (ob leeg hauv pawg neeg tsawg, ib pawg hauv cov koob tshuaj nruab nrab, thiab plaub hauv pawg neeg koob tshuaj siab. ) thiab peb (tsis muaj feem cuam tshuam) tau raug soj ntsuam kom hnyav (ob leeg hauv pawg tshuaj nruab nrab thiab ib qho hauv pawg tshuaj siab). Qib 3 kev kho mob tau tuaj koom cov xwm txheej tsis zoo feem ntau tshwm sim nyob rau hauv pawg koob tshuaj siab (yim [3 feem pua] ntawm 241) dua li ntawm pawg koob tshuaj qis (plaub [2 feem pua] ntawm 240) thiab pab pawg tshuaj nruab nrab (ob [<1%] of="" 240);="" these="" grade="" 3="" events="" included="" two="" events="" of="" grade="" 3="" hypertension="" assessed="" as="" related="" to="" the="" study="" vaccine.="" no="" adverse="" events="" led="" to="" study="" discontinuation,="" and="" no="" adverse="" events="" of="" special="" interest="" were="" reported.="" four="" saes="" were="" reported="" (two="" in="" each="" of="" the="" medium-dose="" and="" high-dose="" groups),="" none="" of="" which="" were="" considered="" by="" the="" investigator="" or="" the="" sponsor="" to="" be="" related="" to="" the="" study="" vaccine.="" solicited="" reactions="" and="" unsolicited="" adverse="" events="" and="" reactions="" tended="" to="" be="" reported="" less="" frequently="" in="" participants="" with="" at="" least="" one="" high-risk="" medical="" condition="" compared="" with="" those="" without="" any="" high-risk="" medical="" condition="" (appendix="" pp="" 17–19).="" the="" safety="" and="" reactogenicity="" profiles="" were="" similar="" between="" participants="" who="" were="" sars-cov-2="" naive="" on="" day="" 1="" and="" those="" who="" were="" non-native="" on="" day="" 1="" (appendix="" pp="">

Ntawm 611 tus neeg koom nrog hauv cov txheej txheem kev tshuaj xyuas ib zaug, 598 (98 feem pua) muaj cov ntaub ntawv txaus los txiav txim siab SARS-CoV-2 tsis zoo nyob rau hnub 1 thiab hnub 22: 521 (85 feem pua) tsis paub thiab 77 (13 feem pua. ) tsis paub. Cov naj npawb ntawm cov neeg tsis paub lus thiab tsis paub tsis meej yog sib npaug ntawm cov pab pawg kho mob: 168 (84 feem pua) ntawm 201 tus neeg koom hauv pab pawg tsawg, 177 (86 feem pua) ntawm 207 hauv pawg tshuaj nruab nrab, thiab 176 (87 feem pua) ntawm 203 nyob rau hauv cov koob tshuaj siab ntau yog cov neeg tsis paub qab hau, thiab 28 (14 feem pua) hauv pab pawg tsawg, 26 (13 feem pua) hauv pawg nruab nrab, thiab 23 (11 feem pua) hauv cov qib siab- pawg koob tshuaj tsis yog-naive.

Ntawm cov neeg koom nrog hauv kev tshuaj xyuas ib tus txheej txheem uas yog SARS-CoV-2 naive, neutralizing antibody GMTs rau D614G variant 14 hnub tom qab txhaj thib ob (hnub 36) yog 2189 (95 feem pua ​​​​CI 1744-2746) hauv Cov koob tshuaj tsawg, 2269 (1792–2873) hauv pawg tshuaj nruab nrab, thiab 2895 (2294–3654) hauv pawg koob tshuaj siab. GMTRs piv rau hnub 36 nrog hnub 1 yog 107 (95 feem pua ​​​​CI 85–135) hauv pawg qis, 11{{70}} (87–140) hauv nruab nrab- pawg koob tshuaj, thiab 141 (111–179) hauv pawg koob tshuaj siab. 158 (98 feem pua) ntawm 162 tus neeg koom yog cov neeg teb (ob zaug lossis ntau dua qhov nce hauv qhov nruab nrab ntawm cov tshuaj tiv thaiv kab mob los ntawm cov hauv paus ntsiab lus) hauv cov pab pawg tsawg dua piv rau 166 (99 feem pua) ntawm 168 hauv pawg nruab nrab koob thiab 163 (98 feem pua) ntawm 166 nyob rau hauv pab pawg neeg siab (table 2). Neutralizing antibody titers tom qab txhaj tshuaj thib ob (hnub 36) zoo li nce nrog cov tshuaj antigen hauv cov hnub nyoog yau tab sis tsis yog rau cov neeg laus; titers tau siab dua rau cov neeg laus dua li cov neeg laus hauv txhua pawg koob tshuaj (daim duab 3A), qhov feem pua ​​​​ntawm cov neeg koom nrog tsawg kawg yog ob zaug lossis plaub zaug nce ntxiv hauv cov tshuaj tiv thaiv kab mob tsis zoo sib xws ntawm cov hnub nyoog (Table 2). Hauv kev soj ntsuam tom qab hoc, qhov loj ntawm neutralizing antibody titers nyob rau hnub 36 zoo ib yam li titers pom nyob rau hauv convalescent sera vaj huam sib luag (2140, 95 feem pua ​​​​CI 1543-2967; table 2), nrog rau qhov sib piv ntawm cov tshuaj tiv thaiv-induced neutralizing-antibody titers rau titers nyob rau hauv lub convalescent vaj huam sib luag ntawm 1·38, 1·85, thiab 2·40 ntawm cov neeg laus thiab 0·76, 0·65, thiab 0·81 ntawm cov neeg laus rau cov koob tshuaj qis, nruab nrab, thiab siab. - koob tshuaj pawg, ntsig txog. Hnub 22 tom qab thawj zaug txhaj tshuaj, neutralizing antibody titers pom qhov tsawg kawg nkaus nce los ntawm lub hauv paus, tsis hais pawg antigen koob, rau ob lub hnub nyoog strata (daim duab 3A; appendix p 20).

Ntawm cov neeg koom nrog uas yog SARS-CoV-2 naive nrog tsawg kawg ib qho kev mob nkeeg uas muaj kev pheej hmoo siab, neutralizing antibody titers rau D614G variant yog zoo ib yam nyob rau hauv antigen-dose pawg nyob rau hauv ob lub hnub nyoog strata. Ntawm cov neeg koom nrog uas tsis paub meej yam tsis muaj kev pheej hmoo siab kho mob, siab dua neutralizing-antibody titers nrog nce koob tshuaj antigen tau pom hauv cov neeg laus. Tom qab ob koob tshuaj, neutralizing antibody titers ntawm cov uas tsis muaj kev pheej hmoo siab yog siab dua cov uas muaj tsawg kawg yog ib qho kev pheej hmoo kho mob nyob rau hauv cov pab pawg nruab nrab thiab cov koob tshuaj siab, tshwj xeeb tshaj yog nyob rau hauv cov hluas hnub nyoog stratum; Qhov kev tshawb pom no tsis tau pom nyob rau hauv pawg neeg tsawg (appendix p 21).

Kev khi cov tshuaj tiv thaiv kab mob hauv 14 hnub tom qab txhaj tshuaj thib ob (hnub 36) ntawm cov neeg koom nrog tsis txaus ntseeg hauv cov txheej txheem kev tshuaj ntsuam xyuas ib txwm muaj siab thoob plaws pawg tshuaj tiv thaiv kab mob, nrog kev nce tsawg tsawg pom tom qab txhaj tshuaj thawj zaug (hnub 21) thiab ntau dua binding-antibody concentrations hauv pawg hnub nyoog yau dua li cov hnub nyoog laus dua rau txhua pawg antigen-dose (appendix pp 22–23; daim duab 4A).

Ntawm cov neeg koom nrog hauv cov txheej txheem kev tshuaj xyuas ib qho uas tsis yog haiv neeg nyob rau hnub 1 lossis hnub 22, lossis ob qho tib si, ua rau cov tshuaj tiv thaiv kab mob tsis zoo (daim duab 3B; cov ntawv ntxiv pp 24-25) thiab khi cov tshuaj tiv thaiv kab mob (daim duab 4B) rau D614G variant nce. ntau tshaj kaum zaug hauv ob lub hnub nyoog strata 21 hnub tom qab txhaj tshuaj ib zaug (hnub 22) hauv txhua pawg tshuaj antigen, xws li hauv txhua pawg tshuaj antigen hnub 22 titers hauv cov neeg koom nrog uas tsis yog haiv neeg siab dua cov neeg tuaj koom uas tau mus txog. tsis muaj qab hau tom qab ob koob tshuaj (hnub 36). Cov titers siab dua thiab nce ntau dua tau pom nyob rau hauv cov hnub nyoog qis dua li cov laus hnub nyoog stratum. GMTs tau nce ntxiv tom qab kev txhaj tshuaj thib ob, txawm hais tias tsawg dua, nrog ze li txhua tus neeg koom hauv txhua pab pawg tau txais tsawg kawg plaub zaug nce hauv cov tshuaj tiv thaiv kab mob titers thiab khi cov tshuaj tiv thaiv kab mob los ntawm hnub 36 (appendix pp 22–25).

Qhov nruab nrab cov tshuaj tiv thaiv kab mob rau cov beta variant tau soj ntsuam nyob rau hnub 36 nkaus xwb (appendix pp 26, 32). Hauv cov neeg koom nrog tsis txaus ntseeg hauv cov txheej txheem kev tshuaj ntsuam xyuas ib zaug, GMTs tau zoo sib xws ntawm cov koob tshuaj qis thiab nruab nrab ntawm pawg, thiab me ntsis siab dua hauv pawg neeg siab, nrog titers kwv yees li kaum npaug qis dua rau D614G variant. Tus qauv ntawm neutralizing antibody cov lus teb rau cov beta variant nrog lub hnub nyoog zoo ib yam li qhov uas tau pom nrog cov lus teb rau D614G variant, nrog cov titers siab dua hauv cov neeg laus dua cov laus. Hauv cov neeg koom nrog uas tsis yog neeg tsis paub qab hau, cov beta-variant GMTs kuj zoo ib yam ntawm cov koob tshuaj qis thiab nruab nrab, nrog cov titers siab dua rau cov pab pawg neeg siab (appendix pp 26 thiab 32).

Ntawm 120 tus neeg koom nrog random muab rau kev ntsuam xyuas ntawm kev tiv thaiv kab mob ntawm tes, cov ntaub ntawv tau muaj rau ib pawg ntawm 104: 36 tus neeg koom nrog hauv pawg neeg tsawg, 31 hauv pawg tshuaj nruab nrab, thiab 37 hauv pawg neeg siab. Kev nce hauv Th1 thiab Th2 cytokines tau pom tom qab txhaj tshuaj tiv thaiv, nrog kev nce ntxiv hauv cytokines tom qab txhaj tshuaj thib ob dua li tom qab thawj zaug (appendix p 27). Kev nce hauv IFN , IL-2, thiab TNF cytokines los ntawm ua ntej txhaj tshuaj tiv thaiv rau hnub 22 thiab hnub 36 tau ntau dua qhov nce rau IL-4, IL-5, thiab IL-13 , nrog rau qhov sib piv ntawm Th1:Th2 cytokines siab dua 1, qhia tias tsis muaj Th2-cell bias nyob rau hauv lub cell-mediated teb (appendix pp 33–34).

maca ginseng cistanchentawmtiv thaiv kab mob

Kev sib tham

Hauv qhov kev tshawb fawb no, ob qhov kev txhaj tshuaj ntawm AS03-adjuvanted SARS-CoV-2 recombinant-protein vaccine, CoV2 preS dTM-AS03, tau qhia txog kev nyab xeeb thiab reactogenicity profile, thiab muaj txiaj ntsig zoo rau cov tshuaj tiv thaiv kab mob thiab cov tshuaj tiv thaiv kab mob ntawm tes. nyob rau hauv cov neeg laus uas yog SARS-CoV-2 naive thiab non-naive, rau tag nrho peb pawg antigen koob tshuaj, thiab nyob rau hauv ob leeg hluas (18–59 xyoo) thiab laus dua (Ntau tshaj los yog sib npaug rau 60 xyoo) muaj hnub nyoog strata.

Tsis muaj kev txhawj xeeb txog kev nyab xeeb raug txheeb xyuas thaum lub sijhawm kawm ib ntus. Hauv txoj kev tshawb fawb tam sim no, cov kev tawm tsam hauv zos thiab cov txheej txheem tau tshaj tawm ntau zaus tom qab txhaj tshuaj thib ob thiab hauv cov hnub nyoog qis dua, ua raws li peb cov kev soj ntsuam dhau los4 thiab nrog rau lwm cov tshuaj tiv thaiv COVID-19.11–14 Cov tshuaj tiv thaiv tsis zoo tau tshaj tawm tsawg dua. nquag thiab mob me dua nrog cov qauv tsim kho hauv txoj kev tshawb fawb tam sim no dua li cov qauv tshuaj ntsuam xyuas hauv theem 1-2 kev sim dhau los.4 Peb tau pom qhov zoo sib xws ntawm cov reactogenicity profile ntawm cov tib neeg uas tsis paub thiab tsis paub, los ntawm kev sib piv nrog cov lus ceeb toom los ntawm lwm cov tshuaj tiv thaiv. ntawm tus nqi siab dua ntawm kev thov cov tshuaj tiv thaiv kab mob seropositive.15,16 AS03-cov tshuaj tiv thaiv kho mob tau pom zoo tsis tu ncua ua rau cov tshuaj tiv thaiv reactogenicity piv nrog cov tshuaj tiv thaiv tsis zoo sib xws, rau cov tshuaj tiv thaiv kab mob khaub thuas sib kis17 thiab rau CoV2 preS dTM hauv peb cov txheej txheem dhau los. 2 txoj kev tshawb no.4 Ntawm kev ceeb toom, qhov sib npaug ntawm cov neeg koom nrog hauv zos thiab cov kab mob tsis zoo tom qab ob koob tshuaj tiv thaiv yog h igher hauv peb txoj kev tshawb fawb dua li yav dhau los tau pom nrog AS03- adjuvanted pandemic influenza vaccines18,19 thiab hauv theem 1 kev sim ntawm AS03-adjuvanted SARS-CoV-2 virus-like particle vaccine14 thiab AS 03-adjuvanted recombinant full-length S protein cov tshuaj tiv thaiv uas tsim tawm hauv CHO hlwb; 13 txawm li cas los xij, qhov kev faib ua feem tau zoo ib yam li cov tau pom hauv kev tshawb fawb soj ntsuam ntawm SARS-CoV-2 mRNA-1273 tshuaj tiv thaiv tom qab ob koob tshuaj tiv thaiv.20 Txawm hais tias peb txoj kev tshawb fawb tsis suav nrog pab pawg placebo, uas yuav cuam tshuam rau kev tshaj tawm ntawm reactogenicity, cov kev soj ntsuam no tau coj los ua ke los qhia tias kev sib xyaw ntawm adjuvant thiab antigen pab txhawb rau cov reactogenicity profile ntawm tus neeg sib tw SARS-CoV{{ 33}} tshuaj tiv thaiv. Cov xwm txheej tsis tu ncua, kev daws tus kheej ntawm cov ntshav siab tsis cuam tshuam nrog cov tsos mob (tshwj tsis yog hauv ib tus neeg koom nrog) tau pom sai tom qab txhaj tshuaj tiv thaiv, uas tuaj yeem ua raws li tus txheej txheem cuam tshuam nrog noradrenergic tawm ib puag ncig lub sijhawm txhaj tshuaj.21,22

Yuav luag txhua tus (Ntau dua lossis sib npaug li 97 feem pua) cov neeg koom nrog uas yog SARS-CoV-2 naive tau nce plaub zaug hauv cov tshuaj tiv thaiv kab mob tsis zoo rau D614G variant ntawm hnub 36, tsis hais hnub nyoog li cas, muaj qhov siab. -Risk kho mob, los yog antigen koob tshuaj. Qhov loj ntawm neutralizing antibody teb tau pom nyob rau hnub 36 nyob rau hauv cov neeg tsis ncaj ncees txoj kev tshawb no yog zoo ib yam li uas tau pom rau ib tug vaj huam sib luag ntawm tib neeg convalescent sera. Cov kev tshawb fawb thaum ntxov ntawm lwm tus neeg sib tw SARS-CoV-2 cov tshuaj tiv thaiv kuj tau pom cov txiaj ntsig zoo sib xws rau cov tshuaj tiv thaiv cov tshuaj tiv thaiv kab mob titers thiab cov ntsuas hauv cov qauv ntshav convalescent, 23–26 uas txhawb nqa lawv txoj kev kho mob ntxiv mus rau kev sim ua tau zoo; Txawm li cas los xij, kev sib piv ncaj qha nrog rau lwm cov tshuaj tiv thaiv SARS-CoV-2 tsis tuaj yeem ua tau nyob rau lub sijhawm no vim tias muaj ntau lub chaw soj nstuam thiab kev ntsuas sib txawv tau siv.

Ntawm cov neeg laus uas tsis yog haiv neeg hauv peb txoj kev tshawb fawb, ib qho kev txhaj tshuaj tau nce D614G neutralizing-antibody titers rau qhov siab dua li cov uas tau pom tom qab ob qhov kev txhaj tshuaj rau cov neeg laus uas tsis paub qab hau thiab tshaj qhov ntsuas hauv convalescent sera. Peb qhov kev tshawb pom tau ua raws li cov lus teb muaj zog ntawm cov tshuaj tiv thaiv kab mob yav dhau los tau pom tom qab ib koob tshuaj BNT162b2 lossis mRNA-1273 SARS-CoV-2 cov tshuaj tiv thaiv hauv cov neeg mob uas yog SARS-CoV-2 seropositive.16 ,27–29 Nws yog qhov nthuav kom nco ntsoov qhov sib txawv ntawm cov lus teb tom qab thawj koob tshuaj rau cov neeg koom nrog uas tsis yog haiv neeg, uas yog vim muaj qhov sib txawv ntawm kev kis kab mob yav dhau los thiab priming, nrog rau lub sijhawm ntawm kev kis kab mob thiab tshuaj tiv thaiv. Cov ntaub ntawv hais txog kev sib raug zoo ntawm kev tiv thaiv tsis tshua muaj.30

Txawm li cas los xij, kev ua haujlwm tsis ntev los no tau ua qauv piv txwv ntawm qhov sib piv ntawm qhov sib piv ntawm cov tshuaj tiv thaiv kab mob hauv cov tshuaj tiv thaiv rau convalescent sera thiab cov tshuaj tiv thaiv tau pom zoo los suav rau qhov sib txawv ntawm kev soj ntsuam thiab convalescent sera.31,32 Hauv cov qauv no, qhov sib piv ntawm 1 cuam tshuam nrog kev siv tshuaj tiv thaiv. ntawm 80–9{13}} feem pua ​​thiab qhov piv ntawm 0·8 cuam tshuam nrog kev siv tshuaj tiv thaiv ntawm 70–80 feem pua. Cov qauv no tau ua raws li cov lus teb tsis zoo ntawm cov tshuaj tiv thaiv kab mob thiab kev ua tau zoo ntawm homologous variants, los yog variants nrog me me drifts. Nyob rau hauv txoj kev tshawb no tam sim no, qhov piv ntawm neutralizing antibody titers rau convalescent sera ranges ntawm 1·38 mus rau 2·40 nyob rau hauv cov pab pawg neeg ntawm cov neeg laus uas tsis paub qab hau, thiab ntawm 0·65 thiab 0·81 ntawm cov laus uas tsis paub qab hau.

Cov lus teb qis dua rau qhov sib txawv ntawm beta pom hauv peb txoj kev tshawb fawb, ua raws li cov ntaub ntawv los ntawm lwm cov tshuaj tiv thaiv kab mob uas tau tso cai los yog tshawb xyuas, 33-35 qhia tias tsis muaj tshuaj tiv thaiv kab mob titers thiab kwv yees tias cov tshuaj tiv thaiv kev ua tau zoo tiv thaiv kab mob heterologous muaj feem yuav qis dua.32 Cov kev sib piv no nrog convalescent sera yuav tsum raug txhais nrog ceev faj vim lawv yog cov kev tshawb nrhiav thiab peb muaj cov ntaub ntawv tsis txaus ntawm cov neeg pub dawb ntawm convalescent sera siv hauv txoj kev tshawb no. Raws li cov ntaub ntawv ib ntus tau piav qhia ntawm no, CoV2 preS dTM-AS03 cov tshuaj tiv thaiv tus neeg sib tw tau nce mus rau theem 3 kev ntsuas kev ua tau zoo (NCT04904549). Raws li cov reactogenicity thiab kev nyab xeeb profiles zoo ib yam nyob rau hauv antigen koob tshuaj pab pawg, kev xaiv ntawm antigen koob tshuaj mus rau theem 3 kev ntsuam xyuas kev ua tau zoo yog feem ntau nyob ntawm qhov soj ntsuam immunogenicity profile nyob rau hauv cov neeg laus uas tsis paub qab hau. Kev xaiv ntawm 10 µg S antigen koob tshuaj rau cov tshuaj tiv thaiv monovalent, tshaj li 5 µg koob tshuaj, tuaj yeem txo qhov muaj peev xwm ntawm kev sib txawv vim tias nws muab ntau dua cov tshuaj tiv thaiv kab mob sib kis tiv thaiv kab mob sib txawv hauv cov tib neeg uas tsis paub qab hau, txawm tias peb tsis tau. saib xyuas kev sib raug zoo ntawm koob tshuaj rau cov beta variant.

Raws li cov qauv uas tau hais los saum toj no ntawm qhov kev kwv yees ua tau zoo ntawm cov tshuaj tiv thaiv kab mob, peb yuav cia siab tias yuav muaj qhov sib txawv ntawm kev tiv thaiv tshuaj tiv thaiv ntawm pawg tshuaj antigen kom txwv. Tsis tas li ntawd, nyob rau hauv cov ntsiab lus ntawm kev sib kis, qhov qis dua cov tshuaj tiv thaiv kab mob yuav hloov mus rau qhov nce ntau hauv cov tshuaj tiv thaiv. Hauv theem 3 txoj kev tshawb fawb, ib qho tshuaj tiv thaiv bivalent AS03-adjuvanted vaccine uas muaj 5 µg D614G antigen thiab 5 µg beta antigen raug soj ntsuam. Vim tias koob tshuaj 5 µg hauv cov neeg tsis paub lus hauv txoj kev tshawb no tau muab cov lus teb homologous neutralizing-antibody zoo ib yam li convalescent sera, nws xav tias cov lus teb zoo sib xws yuav raug tshem tawm los ntawm beta feem ntawm cov tshuaj tiv thaiv bivalent.

Kev faib tawm ntawm cov koob tshuaj tau qhia tias yog lub tswv yim tseem ceeb rau kev ua kom tau raws li qhov xav tau tshuaj tiv thaiv thoob ntiaj teb, 36 tshwj xeeb rau cov tshuaj tiv thaiv kab mob. Cov lus teb tsis zoo ntawm cov tshuaj tiv thaiv kab mob muaj zog tau pom tom qab kev txhaj tshuaj ib zaug ntawm 5 µg antigen-dose formulation hauv cov neeg koom nrog uas yog SARS-CoV-2 non-naive qhia tias ib koob tshuaj ntawm 5 µg CoV2 preS dTM antigen nrog AS03 adjuvant tej zaum yuav yog. txaus rau boosting yav tas los primed cov neeg. Qhov kev tshawb fawb theem 2 no tau raug hloov kho kom suav nrog cov pab pawg ntawm cov tib neeg uas tau txhaj tshuaj tiv thaiv yav dhau los los tshuaj xyuas ib zaug 5 µg antigen koob tshuaj tiv thaiv kab mob.

Tus naj npawb ntawm cov neeg koom hauv txoj kev tshawb fawb no txwv tsis pub muaj kev soj ntsuam ntawm SAEs tsawg thiab cov xwm txheej tsis zoo uas muaj kev txaus siab tshwj xeeb, txawm hais tias txuas ntxiv mus ntxiv thiab cov qauv loj uas tau txais rau qib 3 txoj kev tshawb fawb tom ntej yuav muab cov ntaub ntawv muaj zog rau kev soj ntsuam kev nyab xeeb ntxiv. Txawm hais tias peb tshaj tawm cov lus teb rau cov tshuaj tiv thaiv kab mob rau cov beta variant, qhov sib txawv loj ntawm kev txhawj xeeb thaum lub sij hawm peb tsim txoj kev tshawb no, peb lees paub tias peb tsis tau soj ntsuam cov tshuaj tiv thaiv kab mob rau cov delta variant los yog omicron variant, uas txij li thaum los ua tus tseem ceeb. circulating variants ntawm kev txhawj xeeb. Lwm qhov kev txwv muaj xws li cov ntaub ntawv hais txog kev ua kom lub cev tiv thaiv kab mob tsis muaj los ntawm qhov kev soj ntsuam ib ntus no, thiab cov tshuaj antigen qis dua 5 µg, uas tuaj yeem muaj txiaj ntsig zoo rau kev txhawb nqa cov tib neeg, tsis raug ntsuas ntawm no.

Hauv cov ntsiab lus, ob koob tshuaj ntawm CoV2 preS dTM-AS03 tus neeg sib tw txhaj tshuaj tiv thaiv tau pom tias muaj kev nyab xeeb thiab muaj kev tiv thaiv kab mob hauv cov neeg laus uas tsis paub qab hau rau SARS-CoV-2, suav nrog rau cov neeg muaj hnub nyoog 60 xyoo thiab laus dua thiab cov neeg muaj siab- pheej hmoo kho mob. Raws li cov txiaj ntsig ntawm cov txiaj ntsig no, ob lub qauv ntawm CoV2 preS dTM-AS03 cov tshuaj tiv thaiv tus neeg sib tw, monovalent D614G, thiab bivalent D614G thiab tshuaj tiv thaiv beta variant, tab tom ua qhov kev ntsuas kev ua tau zoo hauv theem 3 kev sim. Tsis tas li ntawd, qhov siab nruab nrab ntawm cov titers thiab kev nyab xeeb tau txais tom qab ib koob tshuaj tiv thaiv ib zaug pom hauv cov neeg koom nrog cov pov thawj ntawm yav dhau los SARS-CoV-2 tus kab mob qhia tau tias muaj peev xwm tsim cov tshuaj tiv thaiv qis dua, thiab kev txhaj tshuaj ib zaug. , siv los ua ib qho kev txhawb zog rau cov neeg laus uas tau ua ntej primed.

cistanche wrkungntawmtiv thaiv kab mob

Cov ntaub ntawv

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