Abstract
Neutralizing antibodies (nAbs) that target the SARS-CoV-2 spike protein have received emergency use approval for treatment of COVID-19. However, with the emergence of variants of concern, there is a need for new treatment options. We report a format that enables modular assembly of bi-paratopic tetravalent nAbs with antigen-binding sites from two distinct nAbs. The tetravalent nAb purifies in high yield and exhibits biophysical characteristics that are comparable to those of clinically used therapeutic antibodies. The tetravalent nAb binds to the spike protein trimer at least 100-fold more tightly than bivalent IgGs (apparent K D < 1 pM) and neutralizes a broad array of SARS-CoV-2 pseudoviruses, chimeric viruses, and authentic viral variants with high potency. Together, these results establish the tetravalent diabody-Fc-Fab as a robust, modular platform for rapid production of drug-grade nAbs with potencies and breadth of coverage that greatly exceed those of conventional bivalent IgGs.
Keywords: CP: Immunology; CP: Microbiology; RBD; S protein; SARS-CoV-2; antibody; bi-paratopic; bispecific; mutational escape; neutralization; passive immunotherapy; virus variant.
【저자키워드】 SARS-CoV-2, S protein, antibody, neutralization, RBD, CP: Immunology, CP: Microbiology, Passive immunotherapy, bi-paratopic, bispecific, mutational escape, virus variant., 【초록키워드】 COVID-19, Treatment, viruses, immunology, antibodies, Microbiology, S protein, Neutralizing antibodies, antibody, neutralization, variant, variants of concern, virus, variants, Spike protein, Coverage, Viral, Characteristics, SARS-CoV-2 spike protein, therapeutic, viral variant, platform, NAb, breadth, Emergency use, chimeric, pseudoviruses, high potency, treatment of COVID-19, NAbs, approval, trimer, IgGs, tetravalent, SARS-CoV-2 pseudoviruses, neutralizes, format, neutralize, bivalent IgG, robust, bind, clinically, the spike protein, comparable, exhibit, the SARS-CoV-2, 【제목키워드】 SARS-CoV-2 variant,