SARS-CoV-2 neutralization

On the 11th of March 2020 the World Health Organization declared the coronavirus outbreak a pandemic. The coronavirus, or more specifically SARS-CoV-2, causing the respiratory illness COVID-19 was spreading worldwide. The symptoms of COVID-19 are highly variable ranging from a mild cough to sever respiratory failure. So far millions of patients all over the world have died, indicating the severeness of the pandemic.

SARS-CoV-2 has four structural proteins, namely the spike, envelope, membrane, and nucleocapsid proteins. Whereas the nucleocapsid protein holds the RNA genome inside the virus, the other three proteins form the outside viral envelop. The spike proteins within the envelop are able to bind ACE2 proteins, which are present on human cells, and thereby enable viral entry. Once inside, the virus releases its RNA and forces the cell to produce copies of the virus to infect more cells. Due to the abundant ACE2 expression on type II alveolar cells in the lungs, the respiratory tract is severely affected resulting in many of the COVID-19 symptoms.

Monoclonal antibodies have shown their therapeutic value in neutralizing viruses and thereby prevent viral replication. By binding the spike protein within the SARS-CoV-2 envelop, the antibody can prevent binding to cellular ACE2 and entry into the human cell. Immunotherapy can thereby result in a decrease in viral load, reduce the severity of symptoms and even prevent death. Since the virus continuously evolves and new SARS-CoV-2 mutants are emerging which express variants of the spike protein it is important to target multiple virus variants. Within this program at AbSano we aim to develop antibodies which will aid in the global fight against COVID-19. We believe that these antibodies have great therapeutic value and will significantly benefit COVID-19 patients.

In SARS-CoV-2 project 1, we have generated a convalescent SARS-CoV-2 patient phage-display library. Using this library we have identified antibodies which are able to interfere with spike-ACE2 binding. Within our antibody discovery pipeline, we have developed neutralizing antibody cocktails reactive against the original SARS-CoV-2 as well as its variants (PCT/EP2022/062777).

In SARS-CoV-2 project 2, we have isolated spike protein specific B-cells from over 50 convalescent SARS-CoV-2 patients. The B-cells were cultured and cells producing antibodies with binding and neutralizing properties were selected against different SARS-CoV-2 variants including Delta and Omicron. The sequences of the antibodies were elucidated, and antibodies expressed and further analyzed. Using this method, we have developed a large set of strongly neutralizing antibodies reactive against SARS-CoV-2 virus variants that show superior activity versus state of the art published antibodies (patent application filing initiated).