tetano
Editor, Senior Moderator
Nat Immunol
. 2021 Oct 29.
doi: 10.1038/s41590-021-01068-z. Online ahead of print.
Low-dose in vivo protection and neutralization across SARS-CoV-2 variants by monoclonal antibody combinations
Vincent Dussupt[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Rajeshwer S Sankhala[SUP] #[/SUP][SUP] 1 3 [/SUP], Letzibeth Mendez-Rivera[SUP] 2 3 [/SUP], Samantha M Townsley[SUP] 2 3 [/SUP], Fabian Schmidt[SUP] 4 [/SUP], Lindsay Wieczorek[SUP] 2 3 [/SUP], Kerri G Lal[SUP] 1 2 3 [/SUP], Gina C Donofrio[SUP] 2 3 [/SUP], Ursula Tran[SUP] 2 3 [/SUP], Nathaniel D Jackson[SUP] 1 2 3 [/SUP], Weam I Zaky[SUP] 2 3 [/SUP], Michelle Zemil[SUP] 2 3 [/SUP], Sarah R Tritsch[SUP] 5 [/SUP], Wei-Hung Chen[SUP] 1 3 [/SUP], Elizabeth J Martinez[SUP] 1 3 [/SUP], Aslaa Ahmed[SUP] 6 [/SUP], Misook Choe[SUP] 1 3 [/SUP], William C Chang[SUP] 1 3 [/SUP], Agnes Hajduczki[SUP] 1 3 [/SUP], Ningbo Jian[SUP] 2 3 [/SUP], Caroline E Peterson[SUP] 1 3 [/SUP], Phyllis A Rees[SUP] 1 3 [/SUP], Magdalena Rutkowska[SUP] 4 [/SUP], Bonnie M Slike[SUP] 2 3 [/SUP], Christopher N Selverian[SUP] 7 [/SUP], Isabella Swafford[SUP] 2 3 [/SUP], I-Ting Teng[SUP] 8 [/SUP], Paul V Thomas[SUP] 1 3 [/SUP], Tongqing Zhou[SUP] 8 [/SUP], Clayton J Smith[SUP] 9 [/SUP], Jeffrey R Currier[SUP] 6 [/SUP], Peter D Kwong[SUP] 8 [/SUP], Morgane Rolland[SUP] 2 3 [/SUP], Edgar Davidson[SUP] 7 [/SUP], Benjamin J Doranz[SUP] 7 [/SUP], Christopher N Mores[SUP] 5 [/SUP], Theodora Hatziioannou[SUP] 4 [/SUP], William W Reiley[SUP] 10 [/SUP], Paul D Bieniasz[SUP] 4 11 [/SUP], Dominic Paquin-Proulx[SUP] 2 3 [/SUP], Gregory D Gromowski[SUP] 6 [/SUP], Victoria R Polonis[SUP] 2 [/SUP], Nelson L Michael[SUP] 12 [/SUP], Kayvon Modjarrad[SUP] 1 [/SUP], M Gordon Joyce[SUP] 13 14 [/SUP], Shelly J Krebs[SUP] 15 16 17 [/SUP]
Affiliations
Abstract
Prevention of viral escape and increased coverage against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern require therapeutic monoclonal antibodies (mAbs) targeting multiple sites of vulnerability on the coronavirus spike glycoprotein. Here we identify several potent neutralizing antibodies directed against either the N-terminal domain (NTD) or the receptor-binding domain (RBD) of the spike protein. Administered in combinations, these mAbs provided low-dose protection against SARS-CoV-2 infection in the K18-human angiotensin-converting enzyme 2 mouse model, using both neutralization and Fc effector antibody functions. The RBD mAb WRAIR-2125, which targets residue F486 through a unique heavy-chain and light-chain pairing, demonstrated potent neutralizing activity against all major SARS-CoV-2 variants of concern. In combination with NTD and other RBD mAbs, WRAIR-2125 also prevented viral escape. These data demonstrate that NTD/RBD mAb combinations confer potent protection, likely leveraging complementary mechanisms of viral inactivation and clearance.
. 2021 Oct 29.
doi: 10.1038/s41590-021-01068-z. Online ahead of print.
Low-dose in vivo protection and neutralization across SARS-CoV-2 variants by monoclonal antibody combinations
Vincent Dussupt[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Rajeshwer S Sankhala[SUP] #[/SUP][SUP] 1 3 [/SUP], Letzibeth Mendez-Rivera[SUP] 2 3 [/SUP], Samantha M Townsley[SUP] 2 3 [/SUP], Fabian Schmidt[SUP] 4 [/SUP], Lindsay Wieczorek[SUP] 2 3 [/SUP], Kerri G Lal[SUP] 1 2 3 [/SUP], Gina C Donofrio[SUP] 2 3 [/SUP], Ursula Tran[SUP] 2 3 [/SUP], Nathaniel D Jackson[SUP] 1 2 3 [/SUP], Weam I Zaky[SUP] 2 3 [/SUP], Michelle Zemil[SUP] 2 3 [/SUP], Sarah R Tritsch[SUP] 5 [/SUP], Wei-Hung Chen[SUP] 1 3 [/SUP], Elizabeth J Martinez[SUP] 1 3 [/SUP], Aslaa Ahmed[SUP] 6 [/SUP], Misook Choe[SUP] 1 3 [/SUP], William C Chang[SUP] 1 3 [/SUP], Agnes Hajduczki[SUP] 1 3 [/SUP], Ningbo Jian[SUP] 2 3 [/SUP], Caroline E Peterson[SUP] 1 3 [/SUP], Phyllis A Rees[SUP] 1 3 [/SUP], Magdalena Rutkowska[SUP] 4 [/SUP], Bonnie M Slike[SUP] 2 3 [/SUP], Christopher N Selverian[SUP] 7 [/SUP], Isabella Swafford[SUP] 2 3 [/SUP], I-Ting Teng[SUP] 8 [/SUP], Paul V Thomas[SUP] 1 3 [/SUP], Tongqing Zhou[SUP] 8 [/SUP], Clayton J Smith[SUP] 9 [/SUP], Jeffrey R Currier[SUP] 6 [/SUP], Peter D Kwong[SUP] 8 [/SUP], Morgane Rolland[SUP] 2 3 [/SUP], Edgar Davidson[SUP] 7 [/SUP], Benjamin J Doranz[SUP] 7 [/SUP], Christopher N Mores[SUP] 5 [/SUP], Theodora Hatziioannou[SUP] 4 [/SUP], William W Reiley[SUP] 10 [/SUP], Paul D Bieniasz[SUP] 4 11 [/SUP], Dominic Paquin-Proulx[SUP] 2 3 [/SUP], Gregory D Gromowski[SUP] 6 [/SUP], Victoria R Polonis[SUP] 2 [/SUP], Nelson L Michael[SUP] 12 [/SUP], Kayvon Modjarrad[SUP] 1 [/SUP], M Gordon Joyce[SUP] 13 14 [/SUP], Shelly J Krebs[SUP] 15 16 17 [/SUP]
Affiliations
- PMID: 34716452
- DOI: 10.1038/s41590-021-01068-z
Abstract
Prevention of viral escape and increased coverage against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern require therapeutic monoclonal antibodies (mAbs) targeting multiple sites of vulnerability on the coronavirus spike glycoprotein. Here we identify several potent neutralizing antibodies directed against either the N-terminal domain (NTD) or the receptor-binding domain (RBD) of the spike protein. Administered in combinations, these mAbs provided low-dose protection against SARS-CoV-2 infection in the K18-human angiotensin-converting enzyme 2 mouse model, using both neutralization and Fc effector antibody functions. The RBD mAb WRAIR-2125, which targets residue F486 through a unique heavy-chain and light-chain pairing, demonstrated potent neutralizing activity against all major SARS-CoV-2 variants of concern. In combination with NTD and other RBD mAbs, WRAIR-2125 also prevented viral escape. These data demonstrate that NTD/RBD mAb combinations confer potent protection, likely leveraging complementary mechanisms of viral inactivation and clearance.