Ithimba lososayensi eliholwa uDkt. Su-Jun Deng ovela ku-biologics ye-Jemincare R&D Center, kanye nelinye ithimba lososayensi abavela ku-SIMM ye-CAS, eliholwa nguProfesa H. Eric Xu kanye noDkt. Wanchao Yin, abaqinisekisanga nje kuphela ukubopha kanye ne-pseudovirus neutralization. umsebenzi we-JMB2002 ngokumelene nokuhluka kwe-Omicron, kodwa futhi yaxazulula izakhiwo ze-Omicron spike protein eyinkimbinkimbi nge-ACE2 ne-JMB2002 ngokulandelanayo (Umfanekiso 1 kanye noMfanekiso 2). Imizamo yocwaningo ehlanganyelwe yembule izindlela zokwanda kokutheleleka kanye nokuphunyuka kwamasosha omzimba okuhlukile kwe-Omicron ezingeni lamangqamuzana, futhi yabonisa indlela eyingqayizivele yokubopha ye-JMB2002 ehlukile kuwo wonke ama-NAbs abikiwe. Okutholakele okuningiliziwe kwezici zenoveli zokuhluka kwe-Omicron kanye ne-JMB2002 kushicilelwe kuwebhusayithi ye-bioRxiv preprint (Reference 1).
Imiphumela yakamuva yocwaningo ibonise ukuthi i-JMB2002 inomsebenzi obophayo ophezulu kokuhluka kwe-Omicron futhi yabonisa umsebenzi onamandla we-Omicron pseudovirus neutralization (Umfanekiso 2A, 2B). Kuyakhuthaza uma kucatshangelwa ukuthi izidakamizwa eziningi ezigunyazwe futhi ezisezingeni lomtholampilo ze-SARS-CoV-2 zilahlekelwe umsebenzi wazo wokungathathi hlangothi noma zibonise amandla anciphisa kakhulu ngenxa yokuguqulwa kaningi kweprotein ye-spike ekuhlukeni kwe-Omicron.
Esinye isizathu sokutheleleka okuthuthukisiwe kokuhluka kwe-Omicron ukuthi iphrotheni yayo eyi-spike i-RBD (Isizinda Esihlanganisa I-Receptor Binding) inekhono eliphakeme lokubopha i-SARS-CoV-2 receptor ACE2 kunaleyo yohlobo lwasendle. Kunezidingo ezisheshayo zokuthuthukisa amasosha omzimba athile okwelapha aqondise ukwahluka kwe-Omicron. Ososayensi abavela e-Jemincare bathola ukuthi ukuhlobana okubophezelayo kwe-JMB2002 Fab kuphrotheni ye-spike ye-Omicron ehlukile iphakeme ngokuphindwe ka-4 kunaleyo ye-WT (Umfanekiso 2A). Okubaluleke nakakhulu, iqembu likaprofesa H. Eric Xu lixazulule isakhiwo se-complex ye-Omicron spike trimer eboshelwe ku-JMB2002 (Umfanekiso 2C), isakhiwo sibonisa ukuthi i-JMB2002 ibophezela ngemuva kwe-RBD, isiqephu esibophezelayo esiyingqayizivele esine-conformation yenoveli (Figure 2D) . Iphakamisa ukuthi i-JMB2002 iyikilasi elisha le-SARS-CoV-2 evimbela amasosha omzimba asebenza ngendlela ebophayo ehlukile kuwo wonke ama-NAbs abikiwe, ahlukaniswa njengesigaba V NAb. Imiphumela evela ekuhlolweni kokungathathi hlangothi kwe-pseudovirus ibonisa ukuthi i-JMB2002 iyi-antibody engathathi hlangothi eqondise yonke i-WHO VOC ngaphandle kokuhlukile kwe-Delta.
I-JMB2002 iqede ukuhlolwa komtholampilo kwesigaba I e-China
NgoJuni 2021, i-JMB2002 iqede uhlolo lomtholampilo lweSigaba I kubanikeli abanempilo e-China ngokuphepha okuhle kakhulu kanye nezakhiwo ze-PK ezifiselekayo. NgoMashi 2021, i-JMB2002 igunyazelwe isilingo somtholampilo e-US (IND 154745). Okwamanje, i-Jemincare ikhiqize isidakamizwa esanele se-JMB2002 ukuze kuqhutshekwe nophenyo lomtholampilo esikalini se-bioreactor esingu-2000L.
LOKHO ONGAKUTHATHE KULESI SIHLOKO:
- Iqembu lika-Eric Xu lixazulule ukwakheka kwe-complex ye-Omicron spike trimer eboshelwe ku-JMB2002 (Umfanekiso 2C), isakhiwo sibonisa ukuthi i-JMB2002 ibophezela ngemuva kwe-RBD, isiqephu esiyingqayizivele esibophayo esine-conformation yenoveli (Umfanekiso 2D).
- I-Wanchao Yin, ayiqinisekisanga nje kuphela umsebenzi wokubopha kanye ne-pseudovirus wokungathathi hlangothi kwe-JMB2002 ngokumelene nokuhluka kwe-Omicron, kodwa futhi yaxazulula izakhiwo ze-Omicron spike protein eyinkimbinkimbi ne-ACE2 ne-JMB2002 ngokulandelanayo (Umfanekiso 1 kanye noMfanekiso 2).
- Imizamo yocwaningo ehlanganyelwe yembule izindlela zokwanda kokutheleleka kanye nokuphunyuka kwamasosha omzimba okuhlukile kwe-Omicron ezingeni lamangqamuzana, futhi yabonisa indlela eyingqayizivele yokubopha ye-JMB2002 ehlukile kuwo wonke ama-NAbs abikiwe.