Nanobody Repertoires for Exposing Vulnerabilities of SARS-CoV-2.

Autor: Mast FD; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, Washington, USA., Fridy PC; Laboratory of Cellular and Structural Biology, The Rockefeller University, New York, New York 10065, USA., Ketaren NE; Laboratory of Cellular and Structural Biology, The Rockefeller University, New York, New York 10065, USA., Wang J; Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, New York, New York 10065, USA., Jacobs EY; Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, New York, New York 10065, USA., Olivier JP; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, Washington, USA., Sanyal T; Department of Bioengineering and Therapeutic Sciences, Department of Pharmaceutical Chemistry, California Institute for Quantitative Biosciences, Byers Hall, 1700 4th Street, Suite 503B, University of California, San Francisco, San Francisco, CA 94158, USA., Molloy KR; Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, New York, New York 10065, USA., Schmidt F; Laboratory of Retrovirology, The Rockefeller University, New York, New York 10065, USA., Rutkowska M; Laboratory of Retrovirology, The Rockefeller University, New York, New York 10065, USA., Weisblum Y; Laboratory of Retrovirology, The Rockefeller University, New York, New York 10065, USA., Rich LM; Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, Washington, USA., Vanderwall ER; Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, Washington, USA., Dambrauskas N; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, Washington, USA., Vigdorovich V; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, Washington, USA., Keegan S; Center for Health Informatics and Bioinformatics, New York University School of Medicine, New York, NY, USA., Jiler JB; Laboratory of Cellular and Structural Biology, The Rockefeller University, New York, New York 10065, USA., Stein ME; Laboratory of Cellular and Structural Biology, The Rockefeller University, New York, New York 10065, USA., Olinares PDB; Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, New York, New York 10065, USA., Hatziioannou T; Laboratory of Retrovirology, The Rockefeller University, New York, New York 10065, USA., Sather DN; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, Washington, USA.; Department of Pediatrics, University of Washington, Seattle, Washington, USA., Debley JS; Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, Washington, USA.; Department of Pediatrics, University of Washington, Seattle, Washington, USA.; Division of Pulmonary and Sleep Medicine, Seattle Children's Hospital, Seattle, Washington, USA., Fenyö D; Center for Health Informatics and Bioinformatics, New York University School of Medicine, New York, NY, USA., Sali A; Department of Bioengineering and Therapeutic Sciences, Department of Pharmaceutical Chemistry, California Institute for Quantitative Biosciences, Byers Hall, 1700 4th Street, Suite 503B, University of California, San Francisco, San Francisco, CA 94158, USA., Bieniasz PD; Laboratory of Retrovirology, The Rockefeller University, New York, New York 10065, USA.; Howard Hughes Medical Institute, The Rockefeller University, New York, New York 10065, USA., Aitchison JD; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, Washington, USA.; Department of Pediatrics, University of Washington, Seattle, Washington, USA.; Department of Biochemistry, University of Washington, Seattle, Washington, USA., Chait BT; Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, New York, New York 10065, USA., Rout MP; Laboratory of Cellular and Structural Biology, The Rockefeller University, New York, New York 10065, USA.
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2021 Apr 10. Date of Electronic Publication: 2021 Apr 10.
DOI: 10.1101/2021.04.08.438911
Abstrakt: Despite the great promise of vaccines, the COVID-19 pandemic is ongoing and future serious outbreaks are highly likely, so that multi-pronged containment strategies will be required for many years. Nanobodies are the smallest naturally occurring single domain antigen binding proteins identified to date, possessing numerous properties advantageous to their production and use. We present a large repertoire of high affinity nanobodies against SARS-CoV-2 Spike protein with excellent kinetic and viral neutralization properties, which can be strongly enhanced with oligomerization. This repertoire samples the epitope landscape of the Spike ectodomain inside and outside the receptor binding domain, recognizing a multitude of distinct epitopes and revealing multiple neutralization targets of pseudoviruses and authentic SARS-CoV-2, including in primary human airway epithelial cells. Combinatorial nanobody mixtures show highly synergistic activities, and are resistant to mutational escape and emerging viral variants of concern. These nanobodies establish an exceptional resource for superior COVID-19 prophylactics and therapeutics.
Databáze: MEDLINE