A multi-specific, multi-affinity antibody platform neutralizes sarbecoviruses and confers protection against SARS-CoV-2 in vivo

• DOI: 10.1126/scitranslmed.adf4549
• Publication Date: 2023-05-24T17:58:51Z
• Authors: Clare Burn Aschner; Krithika Muthuraman; Iga Kucharska; Hong Cui; Katherine Prieto; Manoj S. Nair; Maple Wang; Yaoxing Huang; Natasha Christie-...; Betty Poon; Jessica Lam; Azmiri Sultana; Robert Kozak; Samira Mubareka; John L. Rubinstein; Edurne Rujas; Bebhinn Treanor; David D. Ho; Arif Jetha; Jean-Philippe Julien
• Keywords: Avidity

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of disease 2019 (COVID-19), has been responsible for a global pandemic. Monoclonal antibodies (mAbs) have used as antiviral therapeutics; however, these therapeutics limited in efficacy by viral sequence variability emerging variants concern (VOCs) and deployment need high doses. In this study, we leveraged multi-specific, multi-affinity antibody (Multabody, MB) platform, derived from human apoferritin protomer, to enable multimerization fragments. MBs were shown be highly potent, neutralizing SARS-CoV-2 at lower concentrations than their corresponding mAb counterparts. mice infected with SARS-CoV-2, tri-specific MB targeting three regions within receptor binding domain was protective 30-fold dose cocktail mAbs. Furthermore, showed vitro that mono-specific potently neutralize VOCs leveraging augmented avidity, even when mAbs lose ability potently, expanded neutralization breadth beyond other sarbecoviruses. Our work demonstrates how avidity multi-specificity combined can confer protection resilience against diversity exceeds traditional monoclonal therapies.