Recently, the research paper on Covid-19 neutralizing antibody finished by the team led by professor Zhao Jincun with the SKLRD in cooperation with such organizations as the Boan Biotech, the Cryoelectron Microscopy Center of Shenzhen Southern University of Science and Technology and National Institutes for Food and Drug Control, was officially published on the sub-journal Cell Discovery of Nature (IF: 38.079) with the title of “Biparatopic antibody BA7208/7125 effectively neutralizes SARS-CoV-2 variants including Omicron BA.1-BA.5”. According to the research findings, the Covid-19 neutralizing antibody BA7208/7125 developed by the team boasts a broad spectrum of neutralizing activity for 18 strains including Omicron BA.1-BA.5, implying that it has the potential to become a candidate drug for the intervention with the Covid-19.

BA7208/7125 are 1+1 biparatopic antibodies, boasting excellent druggability, of which the mAbs BA7208 and BA7125 were acquired through the sequential immunity and sequential screening of spike proteins of multiple variants by means of genetically modified mice of the all human antibody transgenic gene and the phage display technology with independent domestic intellectual property rights.

According to the pseudovirus test in vitro, the antibodies BA7208/7125 boast a broad spectrum of neutralizing activity for the 18 strains including the early variants of the novel coronavirus and the variants of Omicron BA.1-BA.5 detected. The true viral pharmacodynamics research conducted in the mice showed that administered in the forms of injection, nasal spray or atomization, the BA7208/7125 can effectively prevent or treat the infection of Omicron BA.1/BA.2, significantly reduce the pulmonary live virus titer in the animal infection model, basically clear the virus from the lungs and boast an excellent protection effect.

Structural analysis revealed that BA7208 and BA7125 bind to conserved epitope of the RBD, avoiding most mutation-sensitive sites in the spike protein receptor domain (RBD) on the surface of SARS-CoV-2, greatly reducing the risk of losing neutralizing activity against SARS-CoV-2 variants.

Fig. 1 A broad spectrum of neutralizing antibodies are acquired through sequential immunity and screening strategies

Fig. 2 The preventive or therapeutic effect of BA7208/7125 in the mouse infection model by injection, nasal spray or atomization

Fig. 3 Cryoelectron microscopy structure of the trimer compound of BA7208, BA7125 Fab and SARS-CoV-2 Spike

Since the outbreak of the Covid-19, its impact on global health and economy has remained unabated today. With the mutation of virus, the effectiveness of existing neutralizing antibodies and vaccines has declined, so it is an urgent task to develop a broader spectrum of effective neutralizing antibodies. Compared with the mono-therapy, the cocktail therapy (integrating two or more neutralizing monoclonal antibodies (nmAbs)) generally boasts better efficacy and better resistance to the viral escape. The biparatopic antibodies integrating two mAbs boast advantages such as a low production cost, convenience for pre-clinical and clinical development compared with the cocktail therapy.

Original paper：https://www.nature.com/articles/s41421-022-00509-9