Characterization of MW06, a human monoclonal antibody with cross-neutralization activity against both SARS-CoV-2 and SARS-CoV

Jiang, Wen; Wang, Junchao; Jiao, Shasha; Gu, Cheng; Xu, Wei; Chen, Ben; Wang, Rongjuan; Chen, Huilin; Xie, Youhua; Wang, An; Li, Gang; Zeng, Dadi; Zhang, Jinchao; Zhang, Min; Wang, Shuang; Wang, Mingzhu; Gui, Xun

doi:10.1080/19420862.2021.1953683

Cited by 20 publications

(27 citation statements)

References 39 publications

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“…500 Ca. 500 ND ND ND [ 316 ] S2X259 RBD-6 74–213 ND 205 358 458 101 ~ 220 588 [ 262 , 406 ] DZIF-10c e UNK 10 (LV) ND 14 (LV) 170 (LV) ND ND ND ND [ 227 ] MAD0004J08 UNK 4 4 4 ND ND ND ND ND [ 221 ] CAB-B37 RBD-1 ND 63 46 25 34 82 ND 20 [ 413 ] ND no data, RBD receptor-binding domain, UNK unknown, LV authentic live virus assay instead of pseudovirus assay a All numbers converted to nearest integer, and where multiple data were available, ranges spanning those data are given. These numbers are from many different experiments, protocols, laboratories, and using different wild-type comparators (different wild-type viruses and sometimes D614G was used as control/comparator), so the specific numbers may not be exactly comparable.…”

Section: Descriptions Of Key Antibodies Targeting Sars-cov-2mentioning

confidence: 99%

“…Figure 5 A, Structure A. SARS-CoV-2 RBD (purple), with human ACE2 binding site identified (white) (PDB ID 7CH5); Epitope group RBD-1 antibodies: B. Etesevimab (LY-CoV016, CB6) Fab [ 204 , 276 ], PDB ID 7C01; C. Amubarvimab (BRII-196, P2C-1F11) Fab [ 211 , 212 ], PDB ID 7CDI; D. C102 Fab [ 276 ], PDB ID 7K8M; E. HFB30132A (P4A1-2A) Fab [ 235 ], PDB ID 7CJF; F. COR-101 Fab [ 236 , 389 ], PDB ID 73BO; G. BD-629 Fab [ 228 , 277 ], PDB ID 7CH5; H. CC12.3 Fab [ 257 , 277 ], PDB ID 6XC4; Epitope group RBD-2 antibodies: I. S2E12 Fv only [ 299 , 390 ], PDB ID 7K45; J. Casarivimab (REGN10933) Fab [ 205 , 323 ], PDB ID 6XDG; K. Tixagevimab (AZD8895; COV2-2196) Fab [ 210 , 211 , 390 ], PDB ID 7L7E; L. B1.182.1 Fab [ 391 ], PDB ID 7MLZ; M. C144 Fv only [ 217 , 276 ]; a second Fv is shown bound to the distal portion of the RBD as described in the text; PDB ID 7K90; N. HLX70 (P17) Fv only [ 242 , 243 ], PDB ID 7CWL; O. Bamlanivimab (LY3819253; LY-CoV555) Fab [ 203 , 326 ], 7KMG; P. Regdanvimab (CT-P59) Fab [ 206 ], PDB ID 7CM4; Q. LYCovMab BA4101 (CA521) Fv only [ 230 ], PDB ID 7E23; R. COVA2-39 Fab [ 277 , 393 , 394 ], PDB ID 7JMP; S. CV07-250 Fv only [ 277 , 395 ], PDB ID 6XKQ; T. Fab2-4 Fv only [ 277 , 396 ], PDB ID 6XEY. Figure 5 B, Epitope group RBD-4 antibodies: U. P2B-2F6 Fab [ 212 , 213 , 277 ], PDB ID 7BWJ; V. CV07-270 Fab [ 277 , 395 ], PDB ID 6XKP; W. MW05 Fab [ 224 , 316 ], PDB ID 7DK0; X. BD...…”

Section: Descriptions Of Key Antibodies Targeting Sars-cov-2mentioning

confidence: 99%

See 1 more Smart Citation

Passive Immunotherapy Against SARS-CoV-2: From Plasma-Based Therapy to Single Potent Antibodies in the Race to Stay Ahead of the Variants

Strohl

et al. 2022

BioDrugs

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The COVID-19 pandemic is now approaching 2 years old, with more than 440 million people infected and nearly six million dead worldwide, making it the most significant pandemic since the 1918 influenza pandemic. The severity and significance of SARS-CoV-2 was recognized immediately upon discovery, leading to innumerable companies and institutes designing and generating vaccines and therapeutic antibodies literally as soon as recombinant SARS-CoV-2 spike protein sequence was available. Within months of the pandemic start, several antibodies had been generated, tested, and moved into clinical trials, including Eli Lilly’s bamlanivimab and etesevimab, Regeneron’s mixture of imdevimab and casirivimab, Vir’s sotrovimab, Celltrion’s regdanvimab, and Lilly’s bebtelovimab. These antibodies all have now received at least Emergency Use Authorizations (EUAs) and some have received full approval in select countries. To date, more than three dozen antibodies or antibody combinations have been forwarded into clinical trials. These antibodies to SARS-CoV-2 all target the receptor-binding domain (RBD), with some blocking the ability of the RBD to bind human ACE2, while others bind core regions of the RBD to modulate spike stability or ability to fuse to host cell membranes. While these antibodies were being discovered and developed, new variants of SARS-CoV-2 have cropped up in real time, altering the antibody landscape on a moving basis. Over the past year, the search has widened to find antibodies capable of neutralizing the wide array of variants that have arisen, including Alpha, Beta, Gamma, Delta, and Omicron. The recent rise and dominance of the Omicron family of variants, including the rather disparate BA.1 and BA.2 variants, demonstrate the need to continue to find new approaches to neutralize the rapidly evolving SARS-CoV-2 virus. This review highlights both convalescent plasma- and polyclonal antibody-based approaches as well as the top approximately 50 antibodies to SARS-CoV-2, their epitopes, their ability to bind to SARS-CoV-2 variants, and how they are delivered. New approaches to antibody constructs, including single domain antibodies, bispecific antibodies, IgA- and IgM-based antibodies, and modified ACE2-Fc fusion proteins, are also described. Finally, antibodies being developed for palliative care of COVID-19 disease, including the ramifications of cytokine release syndrome (CRS) and acute respiratory distress syndrome (ARDS), are described. Supplementary Information The online version contains supplementary material available at 10.1007/s40259-022-00529-7.

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Section: Descriptions Of Key Antibodies Targeting Sars-cov-2mentioning

confidence: 99%

Section: Descriptions Of Key Antibodies Targeting Sars-cov-2mentioning

confidence: 99%

Passive Immunotherapy Against SARS-CoV-2: From Plasma-Based Therapy to Single Potent Antibodies in the Race to Stay Ahead of the Variants

Strohl

et al. 2022

BioDrugs

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“… Human IgG1 B cells of convalescent pts RBD/NTD Potent neutralizing activity against all major SARS-CoV-2 variants - 75 910–30 Human IgG1 B cells of a convalescent pt RBD - - 76 hSARS2-02 hSARS2-38 Chimeric IgG1 Mouse RBD - - 77 2–36 Human IgG1 B cells of infected pts RBD Cross-reactivity against SARS-CoV-1, SARS-CoV-2, and all current SARS-CoV-2 variants - 20 , 78 58G6, etc. Human IgG B cells of convalescent pts RBD - - 79 MW06 Human IgG1 B cells of a convalescent pt RBD Cross-reactivity against SARS-CoV-1 and SARS-CoV-2; form a cocktail with MW05 against SARS-CoV-2 - 80 1H1, etc. Rabbit IgG Immunized rabbit RBD - - 81 ZRC3308-A7 ...…”

Section: Sars-cov-2 and Conventional Igg Mabsmentioning

confidence: 99%

Therapeutic antibodies for COVID-19: is a new age of IgM, IgA and bispecific antibodies coming?

Zhang

Sun

2022

mAbs

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Early humoral immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are dominated by IgM and IgA antibodies, which greatly contribute to virus neutralization at mucosal sites. Given the essential roles of IgM and IgA in the control and elimination of SARS-CoV-2 infection, the mucosal immunity could be exploited for therapeutic and prophylactic purposes. However, almost all neutralizing antibodies that are authorized for emergency use and under clinical development are IgG antibodies, and no vaccine has been developed to boost mucosal immunity for SARS-CoV-2 infection. In addition to IgM and IgA, bispecific antibodies (bsAbs) combine specificities of two antibodies in one molecule, representing an important alternative to monoclonal antibody cocktails. Here, we summarize the latest advances in studies on IgM, IgA and bsAbs against SARS-CoV-2. The current challenges and future directions in vaccine design and antibody-based therapeutics are also discussed.

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“…The receptor binding domain (RBD) within the S1 region of the S protein exhibits a high degree of mutational plasticity and is prone to accumulate mutations that lead to partial immune-escape [27–33]. The World Health Organization (WHO) has designated several SARS-CoV-2 lineages as Variants of Concern (VOCs), which are more transmissible, more pathogenic, and/or can partially evade host immunity, including the Alpha, Beta, Gamma, Delta variants and the recently identified Omicron variant [27, 34–39]. Some pan-sarbecovirus mAbs have been demonstrated to retain their neutralization activity against these VOCs [40, 41].…”

Section: Introductionmentioning

confidence: 99%

“…The World Health Organization (WHO) has designated several SARS-CoV-2 lineages as Variants of Concern (VOCs), which are more transmissible, more pathogenic, and/or can partially evade host immunity, including the Alpha, Beta, Gamma, Delta variants and the recently identified Omicron variant [27,[34][35][36][37][38][39]. Some pan-sarbecovirus mAbs have been demonstrated to retain their neutralization activity against these VOCs [40,41].…”

Section: Introductionmentioning

confidence: 99%

Potent Neutralization of Omicron and other SARS-CoV-2 Variants of Concern by Biparatopic Human VH Domains

Chen

Martinez

Marti

et al. 2022

Preprint

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The emergence of SARS-CoV-2 variants of concern (VOCs) requires the development of next-generation biologics that are effective against a variety of strains of the virus. Herein, we characterize a human VH domain, F6, which we generated by sequentially panning large phage displayed VH libraries against receptor binding domains (RBDs) containing VOC mutations. Cryo-EM analyses reveal that F6 has a unique binding mode that spans a broad surface of the RBD and involves the antibody framework region. Attachment of an Fc region to a fusion of F6 and ab8, a previously characterized VH domain, resulted in a construct (F6-ab8-Fc) that neutralized Omicron pseudoviruses with a half-maximal neutralizing concentration (IC50) of 4.8 nM in vitro. Additionally, prophylactic treatment using F6-ab8-Fc reduced live Beta (B.1.351) variant viral titers in the lungs of a mouse model. Our results provide a new potential therapeutic against SARS-CoV-2 VOCs - including the recently emerged Omicron variant - and highlight a vulnerable epitope within the spike protein RBD that may be exploited to achieve broad protection against circulating variants.

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Characterization of MW06, a human monoclonal antibody with cross-neutralization activity against both SARS-CoV-2 and SARS-CoV

Cited by 20 publications

References 39 publications

Passive Immunotherapy Against SARS-CoV-2: From Plasma-Based Therapy to Single Potent Antibodies in the Race to Stay Ahead of the Variants

Passive Immunotherapy Against SARS-CoV-2: From Plasma-Based Therapy to Single Potent Antibodies in the Race to Stay Ahead of the Variants

Therapeutic antibodies for COVID-19: is a new age of IgM, IgA and bispecific antibodies coming?

Potent Neutralization of Omicron and other SARS-CoV-2 Variants of Concern by Biparatopic Human VH Domains

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