Bispecific VH/Fab antibodies targeting neutralizing and non-neutralizing Spike epitopes demonstrate enhanced potency against SARS-CoV-2
| العنوان: | Bispecific VH/Fab antibodies targeting neutralizing and non-neutralizing Spike epitopes demonstrate enhanced potency against SARS-CoV-2 |
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| المؤلفون: | Graham Simmons, Josef A. Gramespacher, Irene Lui, Shion A. Lim, Colton J Bracken, Jing Jin, Kevin Leung, Xin X. Zhou, Jia Liu, Paige Solomon, James A. Wells, Susanna K. Elledge, Nicholas J. Rettko, Katarina Pance |
| المصدر: | mAbs article-version (VoR) Version of Record mAbs, vol 13, iss 1 |
| بيانات النشر: | Taylor & Francis, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Phage display, Antibodies, Viral, Epitope, Neutralization, Epitopes, 0302 clinical medicine, Antibodies, Bispecific, Immunology and Allergy, Viral, Neutralizing antibody, Neutralizing, Lung, knob-in-hole, 0303 health sciences, biology, Chemistry, neutralizing antibody, Pharmacology and Pharmaceutical Sciences, Spike Glycoprotein, 5.1 Pharmaceuticals, 030220 oncology & carcinogenesis, Spike Glycoprotein, Coronavirus, Pneumonia & Influenza, Public Health and Health Services, Bispecific, Antibody, Biotechnology, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Immunology, Virus, Antibodies, Vaccine Related, 03 medical and health sciences, Immunoglobulin Fab Fragments, Clinical Research, Biodefense, Report, Potency, Humans, 030304 developmental biology, SARS-CoV-2, Prevention, COVID-19, Pneumonia, Virology, Antibodies, Neutralizing, COVID-19 Drug Treatment, Coronavirus, HEK293 Cells, biology.protein, Immunization |
| الوصف: | 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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1942-0870 1942-0862 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8959f3f68f7b3aeb9f632d43f7a03e59 http://europepmc.org/articles/PMC7939556 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....8959f3f68f7b3aeb9f632d43f7a03e59 |
| قاعدة البيانات: | OpenAIRE |
PDF full text from Publisher | تدمد: | 19420870 19420862 |
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