tetano
Editor, Senior Moderator
MAbs
. Jan-Dec 2021;13(1):1958663.
doi: 10.1080/19420862.2021.1958663.
Development of potent and effective synthetic SARS-CoV-2 neutralizing nanobodies
Maxwell A Stefan[SUP] 1 [/SUP], Yooli K Light[SUP] 1 [/SUP], Jennifer L Schwedler[SUP] 2 [/SUP], Peter R McIlroy[SUP] 2 [/SUP], Colleen M Courtney[SUP] 2 [/SUP], Edwin A Saada[SUP] 1 [/SUP], Christine E Thatcher[SUP] 2 [/SUP], Ashlee M Phillips[SUP] 3 [/SUP], Feliza A Bourguet[SUP] 3 [/SUP], Catherine M Mageeney[SUP] 1 [/SUP], Summer A McCloy[SUP] 3 [/SUP], Nicole M Collette[SUP] 3 [/SUP], Oscar A Negrete[SUP] 2 [/SUP], Joseph S Schoeniger[SUP] 1 [/SUP], Dina R Weilhammer[SUP] 3 [/SUP], Brooke Harmon[SUP] 1 [/SUP]
Affiliations
Abstract
The respiratory virus responsible for coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected nearly every aspect of life worldwide, claiming the lives of over 3.9 million people globally, at the time of this publication. Neutralizing humanized nanobody (V[SUB]H[/SUB]H)-based antibodies (V[SUB]H[/SUB]H-huFc) represent a promising therapeutic intervention strategy to address the current SARS-CoV-2 pandemic and provide a powerful toolkit to address future virus outbreaks. Using a synthetic, high-diversity V[SUB]H[/SUB]H bacteriophage library, several potent neutralizing V[SUB]H[/SUB]H-huFc antibodies were identified and evaluated for their capacity to tightly bind to the SARS-CoV-2 receptor-binding domain, to prevent binding of SARS-CoV-2 spike (S) to the cellular receptor angiotensin-converting enzyme 2, and to neutralize viral infection. Preliminary preclinical evaluation of multiple V[SUB]H[/SUB]H-huFc antibody candidates demonstrate that they are prophylactically and therapeutically effective in vivo against wildtype SARS-CoV-2. The identified and characterized V[SUB]H[/SUB]H-huFc antibodies described herein represent viable candidates for further preclinical evaluation and another tool to add to our therapeutic arsenal to address the COVID-19 pandemic.
Keywords: COVID-19; Nanobody; SARS-CoV-2; neutralizing antibody; phage display.
. Jan-Dec 2021;13(1):1958663.
doi: 10.1080/19420862.2021.1958663.
Development of potent and effective synthetic SARS-CoV-2 neutralizing nanobodies
Maxwell A Stefan[SUP] 1 [/SUP], Yooli K Light[SUP] 1 [/SUP], Jennifer L Schwedler[SUP] 2 [/SUP], Peter R McIlroy[SUP] 2 [/SUP], Colleen M Courtney[SUP] 2 [/SUP], Edwin A Saada[SUP] 1 [/SUP], Christine E Thatcher[SUP] 2 [/SUP], Ashlee M Phillips[SUP] 3 [/SUP], Feliza A Bourguet[SUP] 3 [/SUP], Catherine M Mageeney[SUP] 1 [/SUP], Summer A McCloy[SUP] 3 [/SUP], Nicole M Collette[SUP] 3 [/SUP], Oscar A Negrete[SUP] 2 [/SUP], Joseph S Schoeniger[SUP] 1 [/SUP], Dina R Weilhammer[SUP] 3 [/SUP], Brooke Harmon[SUP] 1 [/SUP]
Affiliations
- PMID: 34348076
- DOI: 10.1080/19420862.2021.1958663
Abstract
The respiratory virus responsible for coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected nearly every aspect of life worldwide, claiming the lives of over 3.9 million people globally, at the time of this publication. Neutralizing humanized nanobody (V[SUB]H[/SUB]H)-based antibodies (V[SUB]H[/SUB]H-huFc) represent a promising therapeutic intervention strategy to address the current SARS-CoV-2 pandemic and provide a powerful toolkit to address future virus outbreaks. Using a synthetic, high-diversity V[SUB]H[/SUB]H bacteriophage library, several potent neutralizing V[SUB]H[/SUB]H-huFc antibodies were identified and evaluated for their capacity to tightly bind to the SARS-CoV-2 receptor-binding domain, to prevent binding of SARS-CoV-2 spike (S) to the cellular receptor angiotensin-converting enzyme 2, and to neutralize viral infection. Preliminary preclinical evaluation of multiple V[SUB]H[/SUB]H-huFc antibody candidates demonstrate that they are prophylactically and therapeutically effective in vivo against wildtype SARS-CoV-2. The identified and characterized V[SUB]H[/SUB]H-huFc antibodies described herein represent viable candidates for further preclinical evaluation and another tool to add to our therapeutic arsenal to address the COVID-19 pandemic.
Keywords: COVID-19; Nanobody; SARS-CoV-2; neutralizing antibody; phage display.