A team of scientists led by Dr. Su-Jun Deng from biologics of Jemincare R&D Center, and another team of scientists from SIMM of CAS, led by Professor H. Eric Xu and Dr. 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. Detailed findings of novel features of Omicron variant and JMB2002 have been published on bioRxiv preprint website (Reference 1).

The latest research results indicated that JMB2002 had high binding activity to the Omicron variant and showed potent Omicron pseudovirus neutralization function (Figure 2A, 2B). It is encouraging considering that most approved and clinical-stage SARS-CoV-2 neutralizing antibody drugs have lost their neutralization activity or have shown significantly reduced neutralizing potency due to multiple mutations of the spike protein in Omicron variant. 

One reason of the enhanced infectivity of Omicron variant is that its spike protein RBD (Receptor Binding Domain) has higher binding ability to the SARS-CoV-2 receptor ACE2 than that of wild type. There are immediate needs for developing specific therapeutic antibodies targeting Omicron variant. Scientists from Jemincare found that the binding affinity of JMB2002 Fab to the spike protein of Omicron variant is 4-fold higher than that of WT (Figure 2A). More importantly, professor H. 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). It suggests that JMB2002 is a new class of SARS-CoV-2 neutralizing antibody with a binding mechanism different from all reported NAbs, classifying as class V NAb. The results from pseudovirus neutralization assay indicate that JMB2002 is a broad-spectrum neutralizing antibody targeting all WHO VOC except the Delta variant (Reference 1).