Monoclonal antibodies targeting two immunodominant epitopes on the Spike protein neutralize emerging SARS-CoV-2 variants of concern

The emergence of new SARS-CoV-2 variants that harbor mutations in the viral S protein raised concern about activity of current vaccines and therapeutic antibodies. CCP participated in the research study aiming to find new tools for COVID-19 therapy based on the novel monoclonal antibodies. The results were recently published in EBioMedicine belonging to the Lancet journals.

Kovacech B, Fialova L, Filipcik P, Skrabana R, Zilkova M, Paulenka-Ivanovova N, Kovac A, Palova D, Rolkova GP, Tomkova K, Csokova NT, Markova K, Skrabanova M, Sinska K, Basheer N, Majerova P, Hanes J, Parrak V, Prcina M, Cehlar O, Cente M, Piestansky J, Fresser M, Novak M, Slavikova M, Borsova K, Cabanova V, Brejova B, Vinař T, Nosek J, Klempa B, Eyer L, Hönig V, Palus M, Ruzek D, Vyhlidalova T, Strakova P, Mrazkova B, Zudova D, Koubkova G, Novosadova V, Prochazka J, Sedlacek R, Zilka N, Kontsekova E. Monoclonal antibodies targeting two immunodominant epitopes on the Spike protein neutralize emerging SARS-CoV-2 variants of concern. EBioMedicine. 2022 Jan 22;76:103818. doi: 10.1016/j.ebiom.2022.103818. Epub ahead of print. PMID: 35078012; PMCID: PMC8782626.

Summary of findings: Newly developed second-generation antibodies were specifically selected for their ability to neutralize the new variants of SARS-CoV-2. AX290 and AX677, two monoclonal antibodies with non-overlapping epitopes, exhibit subnanomolar or nanomolar affinities to the receptor binding domain of the viral Spike protein carrying amino acid substitutions found in the circulating virus variants. The antibodies showed excellent neutralization of an authentic SARS-CoV-2 virus representing strains circulating in Europe in spring 2020 and also the variants of concern B.1.1.7 (Alpha), B.1.351 (Beta) and B.1.617.2 (Delta). In addition, AX677 is able to bind Omicron Spike protein just like the wild type Spike. The combination of the two antibodies prevented the appearance of escape mutations of the authentic SARS-CoV-2 virus. Prophylactic administration of AX290 and AX677, either individually or in combination, effectively reduced viral burden and inflammation in the lungs, and prevented disease in a mouse model of SARS-CoV-2 infection.

A full text is available at eBioMedicine.