Innovative Antibody Therapies Against COVID-19 (INATAC)

Utrecht University, Erasmus Medical center, and Harbour Antibodies develop a multi-specific antibody against SARS-CoV-2 that maintains neutralization efficacy against the new Delta and Omicron variants. Results from this project show that our strategy to couple single domains is an effective method to neutralize viruses, using SARSCoV-2 as a starting point.

The trimeric coronavirus ‘spike’ protein on the virus surface is responsible for entry in human cells. This makes it the only target for neutralizing antibodies or vaccines. The ongoing genetic drift of SARS-CoV-2 Variants Of Concern (VOCs) and the changes in spike jeopardizes the efficacy of vaccines and developed antibody therapeutics. This is illustrated by market withdrawal of all 7 (emergency) authorized and clinical stage antibodies that lost efficacy against BA.1 and/or BA.2 from Regeneron, Eli Lilly, AstraZeneca, and Vir Biotechnology. This demonstrates the need for a new technology to develop antibodies that maintain neutralization potency to VOCs of pandemic viruses.

Our innovative technology can provide avenues to alleviate the morbidity and mortality burdens of current and future pandemics. On the one hand, current vaccines prevent serious disease in most individuals but do not protect against infection, especially new omicron variants BA.4 and BA.5. In addition, there are still unvaccinated individuals for medical reasons or by choice whom would be the target group of antibody-based therapeutics.

The projects’ results are threefold: first, our muti-specific antibody which may be used to alleviate infection. Second, we identified conserved immunogenic and vulnerable sites on the coronavirus spike protein to expose the virus’ weak points. Third, this project’s proof of concept for a new pipeline to develop broadly-neutralizing antibodies will be very useful to quickly respond to new viruses with pandemic potential.