Tiger team: a panel of human neutralizing mAbs targeting SARS-CoV-2 spike at multiple epitopes

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IIBR is a governmental, cutting-edge applicable research institute, specializing in the fields of biology, chemistry and environmental sciences.
As a governmental research institute, our biology division’s activities are concentrated around applied biomedical research. We focus on the critical needs of healthcare systems, especially during crisis and emergency situations.​​

Our in-depth understanding of the underlining pathology of biological agents, combined with advanced treatment modalities and state-of-the-art antibody engineering, enable our engineering team to develop unique antibody-based solutions for passive therapy against dangerous pathogens. This platform can be applied to any infectious disease agent, by tailoring the best immunization strategies and isolating the antibodies with the desired specificities.

Our skills and expertise enable systematic process development starting from proof of concept material generation for preclinical programs to clinical trials according to international regulatory guidelines.​

When news started to emerge about the COVID-19 pandemic caused by SARS-Cov-2, we were prepared. In fact, for years, we were concerned with the idea of a coming worldwide crossing borders pandemic. We therefore sought to establish strong capabilities in advance to be used in such a scenario. Indeed, by February 2020, we were assigned by Israeli PM Netanyahu, to develop antibodies and a vaccine against SARS-Cov-2 for the Israeli population.

Our first strategy was to attract antibodies from vaccinated animals using single cell sorting and apply human adjustments afterward. We are a small group of scientists but a very committed one. Each and every one of us worked, in shifts, around the clock. Each and every one of us brought “to the bench” his/her own personality, scientific knowledge and experience but we all had the same goal - to protect the population of Israel and we performed like a highly skilled Orchestra.

And so, in a very short time, we managed to arrange all the required reagents that were necessary for the isolation and characterization of SARS-Cov-2 specific antibodies. In less than a month, the SARS-Cov-2 trimeric spike glycoprotein (S), subunits S1 and S2, the receptor binding domain (RBD) and S1-N-terminal domain (NTD) were successfully expressed in mammalian cells, purified and were functionally evaluated.

But unlike his other family members, SARS-Cov-2 had his own strategy and made a swift “Aliyah” to Israel which allowed us to form a new strategy and use human patients’ samples.

We chose phage display strategy for the enrichment and isolation of antibodies from patients’ samples. We performed the enrichment against the variety of SARS-Cov-2 spike related antigens and by May 2020 we managed to develop a panel of monoclonal neutralizing antibodies. These neutralizing antibodies were shown to recognize distinct epitopes on the viral spike RBD, therefore they represent a promising basis for the design of efficient combined treatment of COVID-19 patients or for prophylactic immunization.

As of September 2020, a patent application was filed and selected antibodies are now in the process of mass production.

To be continued……

The full article can be found at https://www.nature.com/articles/s41467-020-18159-4

Learn more about IIBR https://iibr.gov.il/Pages/home.aspx

Shmuel Yitzhaki, Ph.D.

Head of Biology Division, IIBR

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