Sehlopha sa bo-rasaense se etelletsoeng pele ke Dr. Su-Jun Deng ho tloha biologics ea Jemincare R & D Center, le sehlopha se seng sa bo-rasaense ba SIMM ea CAS, e etelletsoeng ke Moprofesa H. Eric Xu le Dr. Wanchao Yin, ha baa ka ba tiisa feela hore ho tlama le pseudovirus neutralization. ts'ebetso ea JMB2002 khahlano le mofuta oa Omicron, empa hape e rarollotse meaho ea protheine ea Omicron spike e rarahaneng le ACE2 le JMB2002 ka ho latellana (Setšoantšo sa 1 le Setšoantšo sa 2). Boiteko bo kopaneng ba lipatlisiso bo senotse mekhoa ea ho eketseha ha ts'oaetso le ho phonyoha ha 'mele oa' mele oa mofuta oa Omicron maemong a limolek'hule, mme a bonts'a mokhoa o ikhethileng oa JMB2002 o fapaneng le NAbs tsohle tse tlalehiloeng. Liphuputso tse felletseng tsa likarolo tse ncha tsa mofuta oa Omicron le JMB2002 li phatlalalitsoe webosaeteng ea bioRxiv preprint (Reference 1).
Liphetho tsa morao-rao tsa lipatlisiso li bonts'itse hore JMB2002 e na le ts'ebetso e phahameng e tlamang ho mofuta oa Omicron mme e bonts'itse tšebetso e matla ea Omicron pseudovirus neutralization (Setšoantšo sa 2A, 2B). Hoa khothatsa ha ho nahanoa hore litlhare tse ngata tse amohetsoeng le tse maemong a kliniki tsa SARS-CoV-2 li lahlehetsoe ke ts'ebetso ea tsona ea ho se nke lehlakore kapa li bonts'itse phokotseho e kholo ea ho fokotsa matla ka lebaka la liphetoho tse ngata tsa protheine ea spike ho mofuta oa Omicron.
Lebaka le leng la ts'oaetso e matlafalitsoeng ea mofuta oa Omicron ke hore protheine ea eona ea spike RBD (Receptor Binding Domain) e na le bokhoni bo phahameng ba ho tlama ho SARS-CoV-2 receptor ACE2 ho feta ea mofuta o hlaha. Ho na le litlhoko tsa hang-hang tsa ho hlahisa li-antibodies tse tobileng tse lebisang ho mofuta oa Omicron. Bo-rasaense ba tsoang Jemincare ba fumane hore kamano e tlamang ea JMB2002 Fab ho protheine ea spike ea Omicron variant e phahame ka makhetlo a 4 ho feta ea WT (Figure 2A). Habohlokoa le ho feta, sehlopha sa moprofesa H. Eric Xu se rarollotse sebopeho sa motsoako oa Omicron spike trimer o tlameletsoeng ho JMB2002 (Figure 2C), sebopeho se bonts'a JMB2002 e tlama ka morao ho RBD, epitope e ikhethang e tlamang e nang le conformation ea libuka (Figure 2D) . E fana ka maikutlo a hore JMB2002 ke sehlopha se secha sa SARS-CoV-2 se thibelang likokoana-hloko se nang le mochine o tlamang o fapaneng le NAbs tsohle tse tlalehiloeng, tse khethollang e le sehlopha sa V NAb. Liphetho tse tsoang ho pseudovirus neutralization assay li bonts'a hore JMB2002 ke sethibela-mafu se pharalletseng se thibelang likokoana-hloko se shebileng bohle VOC ea WHO ntle le mofuta oa Delta.
JMB2002 e qetile teko ea bongaka ea phase I Chaena
Ka Phuptjane 2021, JMB2002 e qetile teko ea bongaka ea Phase I ho bafani ba phetseng hantle Chaena ba nang le polokeho e ntle le thepa e lakatsehang ea PK. Ka Hlakubele 2021, JMB2002 e amohetsoe bakeng sa teko ea bongaka US (IND 154745). Hajoale, Jemincare e hlahisitse sethethefatsi se lekaneng sa JMB2002 bakeng sa lipatlisiso tse ling tsa bongaka boemong ba 2000L bioreactor scale.
SEO U LOKELANG HO SE NKA HO SEHLOOHO ENA:
- Eric Xu’s group has solved the structure of the complex of Omicron spike trimer bound to JMB2002 (Figure 2C), the structure shows JMB2002 binds to the back of RBD, a unique binding epitope with novel conformation (Figure 2D).
- Wanchao Yin, not only confirmed the binding and pseudovirus neutralization activity of JMB2002 against Omicron variant, but also solved the structures of Omicron spike protein in complex with ACE2 and JMB2002 respectively (Figure 1 and Figure 2).
- Joint research efforts revealed the mechanisms of increased infectivity and immune escape of the Omicron variant at molecular level, and demonstrated the unique binding mechanism of JMB2002 differing from all reported NAbs.
