Bispecific VH/Fab antibodies targeting neutralizing and non-neutralizing Spike epitopes demonstrate enhanced potency against SARS-CoV-2

• Հիմնական հեղինակներ: Shion A. Lim (Հեղինակ), Josef A. Gramespacher (Հեղինակ), Katarina Pance (Հեղինակ), Nicholas J. Rettko (Հեղինակ), Paige Solomon (Հեղինակ), Jing Jin (Հեղինակ), Irene Lui (Հեղինակ), Susanna K. Elledge (Հեղինակ), Jia Liu (Հեղինակ), Colton J. Bracken (Հեղինակ), Graham Simmons (Հեղինակ), Xin X. Zhou (Հեղինակ), Kevin K. Leung (Հեղինակ), James A. Wells (Հեղինակ)
• Ձևաչափ: Գիրք
• Հրապարակվել է: Taylor & Francis Group, 2021-01-01T00:00:00Z.
• Խորագրեր: article
• Առցանց հասանելիություն: Connect to this object online.

Ամփոփում

Numerous neutralizing antibodies that target SARS-CoV-2 have been reported, and most directly block binding of the viral Spike receptor-binding domain (RBD) to angiotensin-converting enzyme II (ACE2). Here, we deliberately exploit non-neutralizing RBD antibodies, showing they can dramatically assist in neutralization when linked to neutralizing binders. We identified antigen-binding fragments (Fabs) by phage display that bind RBD, but do not block ACE2 or neutralize virus as IgGs. When these non-neutralizing Fabs were assembled into bispecific VH/Fab IgGs with a neutralizing VH domain, we observed a ~ 25-fold potency improvement in neutralizing SARS-CoV-2 compared to the mono-specific bi-valent VH-Fc alone or the cocktail of the VH-Fc and IgG. This effect was epitope-dependent, reflecting the unique geometry of the bispecific antibody toward Spike. Our results show that a bispecific antibody that combines both neutralizing and non-neutralizing epitopes on Spike-RBD is a promising and rapid engineering strategy to improve the potency of SARS-CoV-2 antibodies.

Նյութի նկարագրություն

10.1080/19420862.2021.1893426
1942-0870
1942-0862