htLang
Kay / Konesans / Sanisfè

Konesans

Vaksen yo pwovoke iminite selilè ki trè konsève pou SARS-CoV-2 Omicron

Nov 16, 2023

Yo montre varyant SARS-CoV-2 Omicron (B.1.1.529) ki gen anpil mitasyon nan evade yon fraksyon sibstansyèl nan repons antikò netralize ki soti nan vaksen aktyèl yo ki kode pwoteyin Spike WA1/2020 la. Repons iminitè selilè yo, patikilyèman repons selil CD8+ T, pwobableman kontribye nan pwoteksyon kont enfeksyon grav SARS-CoV-22–6. Isit la nou montre ke iminite selilè pwovoke pa vaksen aktyèl kont SARS-CoV-2 trè konsève nan SARS-CoV-2 Omicron Spike pwoteyin. Moun ki te resevwa vaksen Ad26.COV2.S oswa BNT162b2 yo te demontre repons dirab CD8+ ak CD4+ selil T ki espesifik pou Spike yo, ki te montre anpil reaktivite kwaze kont variantes Delta ak Omicron yo, tankou nan subpopulations selilè santral ak efèktè memwa. Medyàn Omicron Spike-espesifik CD8+ repons selil T yo te 82-84% nan WA1/2020 Spike-espesifik CD8+ repons selil T yo. Done sa yo bay yon kontèks iminolojik pou obsèvasyon ke vaksen aktyèl yo toujou montre pwoteksyon solid kont maladi grav ak SARS-CoV-2 Omicron variant malgre repons antikò netralize yo redwi anpil7,8.

Desert ginseng—Improve immunity (8)

cistanche tubulosa-amelyore sistèm iminitè

Klike la a pou w wè pwodwi Cistanche Enhance Immunity

【Mande plis】 Imèl:cindy.xue@wecistanche.com / Whats App: 0086 18599088692 / Wechat: 18599088692

Dènye etid yo te montre ke antikò netralizasyon vaksen yo (NAb) yo redwi anpil nan SARS-CoV-2 Omicron variant1 ki gen anpil mitasyon. Pou evalye kwa-reaktivite repons iminitè selilè vaksen yo te pwovoke kont varyant Omicron SARS-CoV-2, nou te evalye repons selil CD{8+ ak CD{4+ T nan 47 moun ki te pran vaksen an. ak vaksen Ad26.COV2.S ki baze sou vektè adenoviris9 (Johnson & Johnson; n=20) oswa vaksen BNT162b2 ki baze sou mRNA10 (Pfizer; n=27) nan Boston, MA, USA (Done Pwolonje Tablo 1).

Desert ginseng—Improve immunity (12)

benefis cistanche pou gason-ranfòse sistèm iminitè

Repons iminitè umoral

Tout moun yo te SARS-CoV-2 nayif nan istwa epi yo te gen tou repons negatif antikò nan nukleokapsid (Done Pwolonje Fig. 1). Apre vaksinasyon an ak BNT162b2, nou te obsève gwo repons WA1/2020-pseudovirus NAb espesifik nan mwa 1, ki te swiv pa yon gwo bès nan mwa 8 (P <0.{0001, de-ke). Tès Mann–Whitney), jan yo espere11,12 (Fig. 1a). Apre vaksinasyon ak Ad26.COV2.S, te gen premye repons WA1/2020-espesifik pseudovirus NAb ki pi ba anpil nan mwa 1, men repons sa yo te pi dirab e yo te pèsiste nan mwa 8 (ref. 11, 13) (Fig. 1a). Sepandan, yo te obsève minimòm kwa-reyaktif Omicron-espesifik NAb pou tou de vaksen yo (P <0.0001 pou tou de, tès Mann-Whitney de-ke) (Fig. 1a), ki konsistan avèk done ki sot pase yo nan absans la nan ranfòse adisyonèl1. Repons yo nan reseptè-obligatwa domèn-espesifik antikò obligatwa yo te evalye pa ELISA epi yo te montre tandans menm jan an, ak minimòm kwa-reyaktif Omicron reseptè-obligatwa domèn-espesifik antikò obligatwa (Fig. 1b, Pwolonje Done Fig. 2).

Desert ginseng—Improve immunity (2)

cistanche tubulosa-amelyore sistèm iminitè

Repons iminitè selilè

Kontrèman ak repons antikò, repons iminitè selilè Spike-espesifik evalye pa pisin peptide IFN ELISPOT analiz te montre sibstansyèl kwa-reaktivite nan Omicron (Done pwolonje Fig. 3, Tablo siplemantè 1). Apre sa, nou te evalye repons CD8+ ak CD4+ T ki espesifik nan Spike-espesifik pa tès tach cytokine intraselilè (Done Pwolonje Fig. 4, 5, Tablo Siplemantè 1). Ad26.COV2.S pwovoke repons medyàn nan IFN CD8+ selil T yo nan 0.061%, 0.062% ak 0. {30}}.{051% kont WA1/202{0, Delta ak Omicron, respektivman, nan mwa 8 apre vaksinasyon an (Fig. 2a). BNT162b2 pwovoke medyàn Spike-espesifik IFN CD 8+ T selil repons nan 0.028% ak 0.023% kont WA1/2020 ak Omicron, respektivman, nan mwa 8 apre vaksinasyon an (Fig. 2a). Done sa yo sijere ke medyàn Omicron-espesifik CD8+ repons selil T yo te 82-84% kwa-reyaktif ak repons selil T WA1/{2020-espesifik CD{8+ T (valè P la pa t enpòtan ; tès Mann-Whitney de-ke). Spike-espesifik IFN CD4+ repons selil T yo te pwovoke pa Ad26.COV2.S yo te yon medyàn 0.026%, 0.030%, ak 0.029% kont WA1/2020, Delta, ak Omicron, respektivman, ak BNT162b2 te yon medyàn. nan 0.033% ak 0.027% kont WA1/2020 ak Omicron, respektivman, nan mwa 8, ki endike ke medyàn Omicron-espesifik CD4+ repons selil T yo te 82-100% kwa-reyaktif ak WA1/2020- repons espesifik CD4+ selil T (valè P la pa t enpòtan; tès Mann-Whitney de-ke) (figi 2b). Done sa yo montre anpil reaktivite selil CD8+ ak CD4+ T nan Omicron, byenke repons yo ka afekte plis nan kèk moun (figi 3a). Yo te obsève gwo reaktivite Omicron tou pou repons selil T ki sekrete IFN espesifik, ki sekre TNF ak IL-2-sekrete CD8+ ak CD4+ T (Done pwolonje Fig. 6) .

Fig. 1 | Humoral immune responses to Omicron. Antibody responses at months 1 and 8 following final vaccination with Ad26.COV2.S (n = 20) or BNT162b2 (n = 27). a Neutralizing antibody (NAb) titers by a luciferase-based pseudovirus neutralization assay. b, Receptor-binding domain (RBD)-specific binding antibody titers by ELISA. Responses were measured against the SARS-CoV-2 WA1/2020 (WA), B.1.617.2 (Delta), B.1.351 (Beta) and B.1.1.529 (Omicron) variants. Medians (red bars) are depicted and numerically shown.


Figi 1|Repons iminitè umoral nan Omicron. Repons antikò nan mwa 1 ak 8 apre vaksinasyon final la ak Ad26.COV2.S (n=20) oswa BNT162b2 (n=27). yon tit antikò netralize (NAb) pa yon tès netralizasyon pseudoviris ki baze sou luciferase. b, Reseptè-obligatwa domèn (RBD)-espesifik obligatwa antikò tit pa ELISA. Yo te mezire repons yo kont SARS-CoV-2 WA1/2020 (WA), B.1.617.2 (Delta), B.1.351 (Beta) ak B.1.1.529 (Omicron). Médians (bawo wouj) yo reprezante epi yo montre nimerikman.

Kontrèman, moun ki pa pran vaksen yo, moun ki pa enfekte yo te gen yon repons neglijab pou piki espesifik CD8+ ak CD4+ T selil (figi 2a, b). Repons selil T Omicron-espesifik CD8+ ki gen rapò ak repons selil T espesifik WA1/2020- CD{8+ T pou vaksen Ad26.COV2.S pou tou de pwen tan yo (R=0 .78, P < 0.00{01, pant=0.75) ak vaksen BNT162b2 (R=0.56). , P < 0.0001, pant=0.81), byenke de moun te gen yon CD ki pa detekte espesifik pou Omicron8+ Repons selil T apre vaksinasyon ak BNT162b2 (figi 3b). Menm jan an tou, repons selil CD4+ T espesifik Omicron yo te gen rapò ak repons selil T WA1/2020-espesifik CD4+ T pou tou de vaksen Ad26.COV2.S (R=0. 79, P < 0.00{{80}}1, pant=0.83) ak vaksen BNT162b2 (R {{45} }}.90, P <0.0001, pant=0.88) (Fig. 3c). Spike-espesifik IFN CD8+ ak CD{4+ selil T santral (CD45RA− CD{{27+ ) ak efektè (CD45RA− CD27− ) memwa sou-popilasyon Ad26.COV2.S te montre tou anpil kwa-reaktivite nan Delta ak Omicron variants. Nan mwa 8, repons memwa santral selil CD8+ T yo te 0.076%, 0.054%, ak 0.075%, CD8+ repons memwa efektè selil T yo te 0.168%, 0.143% ak 0.146%, CD{{ 77}} Repons memwa santral selil T yo te 0.030%, 0.035% ak 0.038%, ak CD4+ repons memwa efektè selil T yo te 0.102%, 0.094% ak ​​0.083% kont WA1/202, Delta ak Omicron, respektivman ( Fig. 4).

Desert ginseng—Improve immunity (23)

cistanche tubulosa-amelyore sistèm iminitè

Diskisyon

Done nou yo demontre ke Ad26.COV2.S ak BNT162b2 pwovoke iminite selilè kwa-reyaktif kont varyant SARS-CoV-2 ki gen ladan Omicron. Konsistans obsèvasyon sa yo atravè de teknoloji platfòm vaksen diferan (vektè viral ak mRNA) sijere jeneralizasyon rezilta sa yo. Gwo reaktivite kwa-reaktivite nan repons Omicron-espesifik CD8+ ak CD4+ T selil yo diferansye sevè ak rediksyon ki make nan repons antikò espesifik Omicron yo. Done sa yo konsistan avèk etid anvan yo ki te montre pi gwo reyaktivite kwaze repons iminitè selilè vaksen yo pase repons iminitè umoral kont SARS-CoV-2 Alpha, Beta ak Gamma14. Repons selil T yo vize plizyè rejyon nan pwoteyin Spike a, ki konsistan avèk repons iminitè selilè lajman konsève nan Omicron6,14. Reyaktivite kwaze 82-84% repons selil CD8+ T yo bay Omicron an konsistan tou ak prediksyon teyorik ki baze sou mitasyon Omicron yo. Limit etid nou an gen ladan yo sèvi ak gwo dòz peptides ak costimulation nan tès intraselilè cytokine tach, ak mank nan evalye efè a nan mitasyon sou pwosesis antijèn. Etid preklinik yo montre ke selil CD8+ T yo kontribye nan pwoteksyon kont SARS-CoV-2 nan makak rhesus, sitou lè repons antikò yo pa pi bon5. Yo rapòte tou repons CD8+ ak CD4+ T dirab apre enfeksyon ak vaksinasyon2–4,6,11,13,15,16. Etandone wòl selil CD8+ T yo nan elimine enfeksyon viral, li posib ke iminite selilè kontribye anpil nan pwoteksyon vaksen kont maladi SARS-CoV-2 grav. Sa a ka patikilyèman enpòtan pou Omicron, ki dramatikman evade repons antikò netralize yo. Dènye etid yo te montre ke Ad26.COV2.S ak BNT162b2 te bay 85% ak 70% pwoteksyon, respektivman, kont entène lopital akòz Variant Omicron nan Lafrik di sid7,8. Done nou yo bay kontèks iminolojik pou obsèvasyon ke vaksen aktyèl yo toujou bay pwoteksyon solid kont maladi grav akòz varyant Omicron SARS-CoV-2 malgre repons antikò netralize yo redwi anpil.

Fig. 2 | Cellular immune responses to Omicron. T cell responses at months 1 and 8 following final vaccination with Ad26.COV2.S (n = 20) or BNT162b2 (n = 27). a, b, Pooled peptide spike-specific IFNγ CD8+ T cell responses (a) and CD4+ T cell responses (b) by intracellular cytokine staining assays. Responses were measured against the SARS-CoV-2 WA1/2020, B.1.617.2 (Delta) and B.1.1.529 (Omicron) variants. Responses in five unvaccinated, uninfected individuals are also shown. Media backgrounds were subtracted from the specific values. Medians (red bars) are depicted and numerically shown.

Figi 2|Repons iminitè selilè nan Omicron. Repons selil T nan mwa 1 ak 8 apre vaksinasyon final la ak Ad26.COV2.S (n = 20) oswa BNT162b2 (n = 27). a, b, IFN peptide Spike-espesifik CD8+ repons selil T (a) ak repons selil T CD4+ (b) pa tès tach cytokine intraselilè. Repons yo te mezire kont SARS-CoV-2 WA1/2020, B.1.617.2 (Delta) ak B.1.1.529 (Omicron). Yo montre tou repons nan senk moun ki pa vaksinen e ki pa enfekte. Orijin medya yo te soustraksyon nan valè espesifik yo. Médians (bawo wouj) yo reprezante epi yo montre nimerikman.

Fig. 3 | Correlations of variant-specific and WA1/2020-specific cellular immune responses.a, Ratio of Omicron to WA1/2020 CD8+ (top) and CD4+ (bottom) T cell responses in individual participants. b, c, Correlations of log Delta-specific and Omicron-specific to log WA1/2020-specific CD8+ T cell responses (b) and CD4+ T cell responses (c) by intracellular cytokine staining assays. Two-sided unadjusted P and R values for linear regression correlations are shown, and lines of best fit and slopes are depicted.

Figi 3|Korelasyon varyant espesifik ak repons iminitè selilè WA1/2020-espesifik yo.a, Pwopòsyon Omicron ak WA1/2020 CD8+ (anwo) ak CD4+ (anba) repons selil T nan patisipan endividyèl yo. b, c, Korelasyon nan log Delta-espesifik ak Omicron-espesifik nan mòso WA1/2020-espesifik CD8+ repons selil T (b) ak CD4+ repons selil T (c) pa tès tach cytokine intraselilè. Yo montre valè P ak R ki pa ajiste de bò pou korelasyon regression lineyè, epi yo montre liy pi bon anfòm ak pant yo.

Fig. 4 | Cellular immune memory subpopulations to Omicron. Pooled peptide spike-specific IFNγ CD8+ and CD4+ central memory (CD45RA− CD27+ ) and effector memory (CD45RA− CD27− ) T cell responses by intracellular cytokine staining assays at months 1 and 8 following final vaccination with Ad26.COV2.S (n = 20). Responses were measured against the SARS-CoV-2 WA1/2020, B.1.617.2 (Delta), and B.1.1.529 (Omicron) variants. Medians (red bars) are depicted and numerically shown.


Figi 4|Sou-populasyon memwa iminitè selilè nan Omicron. Memwa santral IFN CD8+ ak CD4+ (CD45RA−CD27+) ak memwa efèktè (CD45RA−CD27−) ak memwa efektè (CD45RA−CD27−) IFN espesifik peptides espesifik yo pa tès tach intraselilè cytokine nan mwa. 1 ak 8 apre vaksinasyon final la ak Ad26.COV2.S (n=20). Repons yo te mezire kont SARS-CoV-2 WA1/2020, B.1.617.2 (Delta), ak B.1.1.529 (Omicron). Médians (bawo wouj) yo reprezante epi yo montre nimerikman.

Kontni sou entènèt

Desert ginseng—Improve immunity (13)

cistanche tubulosa-amelyore sistèm iminitè

Nenpòt metòd, referans adisyonèl, rapò rechèch lanati, done sous, done pwolonje, enfòmasyon siplemantè, rekonesans, enfòmasyon revizyon kanmarad; detay sou kontribisyon otè ak enterè konpetisyon; ak deklarasyon done ak disponiblite kòd yo disponib nan https://doi.org/10.1038/s41586-022-04465-y.

Referans

1. Cele, S. et al. Omicron anpil men enkonplètman chape Pfizer BNT162b2 netralizasyon. Nature 602, 654–656 (2022).

2. Dann, JM et al. Memwa iminolojik pou SARS-CoV-2 evalye pou jiska 8 mwa apre enfeksyon. Syans 371, eabf4063 (2021).

3. Sette, A. & Crotty, S. Iminite adaptatif pou SARS-CoV-2 ak COVID-19.Selil184, 861–880 (2021). 

4. Goel, RR et al. Vaksen mRNA pwovoke memwa iminitè dirab pou SARS-CoV-2 ak varyant enkyetid.Syans374, abm0829 (2021).

5. McMahan, K. et al. Korele nan pwoteksyon kont SARS-CoV-2 nan makak rhesus.Lanati590, 630–634 (2021). 

6. Grifoni, A. et al. Objektif repons selil T a coronavirus SARS-CoV-2 nan moun ki gen maladi COVID-19 ak moun ki pa ekspoze.Selil181, 1489–1501.e15 (2020) Detay sou kontribisyon otè ak enterè konpetisyon; ak deklarasyon sou disponiblite done ak kòd yo disponib nanhttps://doi.org/10.1038/s{{2}y.

7. Collie, S., Champion, J., Moultrie, H., Bekker, LG & Gray, G. Efikasite vaksen BNT162b2 kont Variant Omicron nan Lafrik di sid.N. Engl. J. Med.386, 494–496 (2022). 

8. Gray, GE et al. Efikasite vaksen kont admisyon lopital nan travayè swen sante Sid Afriken yo ki te resevwa yon rapèl omològ Ad26.COV2 pandan yon vag Omicron COVID-19: rezilta preliminè etid Sisonke 2 la. Preprint nanmedRxivhttps://doi.org/10.1101/2021.12.28.21268436 (2021).

9. Sadoff, J. et al. Sekirite ak efikasite vaksen yon sèl dòz Ad26.COV2.S kont Covid-19.N. Engl. J. Med.384, 2187–2201 (2021).

10. Polack, FP et al. Sekirite ak efikasite vaksen BNT162b2 mRNA Covid-19 la.N. Engl. J. Med.383, 2603–2615 (2020).

11. Collier, AY et al. Diferans sinetik repons iminitè vaksen Covid-19.N. Engl. J. Med.385, 2010–2012 (2021). 

12. Falsey, AR et al. Netralizasyon SARS-CoV-2 ak dòz vaksen BNT162b2 3.N. Engl. J. Med.385, 1627–1629 (2021). 

13. Barouch, DH et al. Repons iminitè umoral ak selilè dirab 8 mwa apre vaksinasyon Ad26.COV2.S.N. Engl. J. Med.385, 951–953 (2021). 

14. Alter, G. et al. Iminojenisite vaksen Ad26.COV2.S kont varyant SARS-CoV-2 nan imen.Lanati596, 268–272 (2021). 

15. Poon, MML et al. Enfeksyon SARS-CoV-2 jenere memwa iminolojik lokalize nan tisi nan imen.Sci. Imunol.6, eabl9105 (2021).

16. Vidal, SJ et al. Korele nan netralizasyon kont SARS-CoV-2 varyant enkyetid pa seri pandemi bonè.J. Virol.95, e0040421 (2021).

Ou ka renmen tou