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Low-dose in vivo protection and neutralization across SARS-CoV-2 variants by monoclonal antibody combinations.

Vincent Dussupt | Rajeshwer S Sankhala | Letzibeth Mendez-Rivera | Samantha M Townsley | Fabian Schmidt | Lindsay Wieczorek | Kerri G Lal | Gina C Donofrio | Ursula Tran | Nathaniel D Jackson | Weam I Zaky | Michelle Zemil | Sarah R Tritsch | Wei-Hung Chen | Elizabeth J Martinez | Aslaa Ahmed | Misook Choe | William C Chang | Agnes Hajduczki | Ningbo Jian | Caroline E Peterson | Phyllis A Rees | Magdalena Rutkowska | Bonnie M Slike | Christopher N Selverian | Isabella Swafford | I-Ting Teng | Paul V Thomas | Tongqing Zhou | Clayton J Smith | Jeffrey R Currier | Peter D Kwong | Morgane Rolland | Edgar Davidson | Benjamin J Doranz | Christopher N Mores | Theodora Hatziioannou | William W Reiley | Paul D Bieniasz | Dominic Paquin-Proulx | Gregory D Gromowski | Victoria R Polonis | Nelson L Michael | Kayvon Modjarrad | M Gordon Joyce | Shelly J Krebs
Nature immunology | 2021

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.

Pubmed ID: 34716452 RIS Download

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IgBLAST (tool)

RRID:SCR_002873

THIS RESOURCE IS NO LONGER IN SERVICE.Documented on January 4,2023. IgBLAST was developed at NCBI to facilitate analysis of immunoglobulin V region sequences in GenBank. In addition to performing a regular BLAST search, IgBLAST has several additional functions: - Reports the germline V, D and J gene matches to the query sequence. - Annotates the immunoglobulin domains (FWR1 through FWR3). - Matches the returned hits (for databases other than germline genes) to the closest germline V genes, making it easier to identify related sequences. - Reveals the V(D)J junction details such as nucleotide homology between the ends of V(D)J segments and N nucleotide insertions. D and J gene reporting is only for nucleotide sequence search and requires a stretch of five or more nucleotide identity between the query and D or J genes. Sponsors: This resource is supported by the National Center for Biotechnology Information, a division of the U.S. National Library of Medicine.

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