Science 13.08.2021

RESEARCH | REPORTS

68. D. Zhou et al., . Cell 184, 2348–2361.e6 (2021). 89. S. M. Kissler, C. Tedijanto, E. Goldstein, Y. H. Grad, M. Lipsitch, funding provided by the Coronavirus CARES Act. Author
69. G. Cerutti et al., Structure 29, 655–663.e4 (2021). Science 368, 860–868 (2020). contributions: M.Y., D.H., C.-C.D.L., N.C.W., and I.A.W. conceived
70. T. N. Starr et al., Nature 10.1038/s41586-021-03807-6 and designed the study; M.Y., C.-C.D.L., N.C.W., and H.L. expressed
90. J. Lan et al., Nature 581, 215–220 (2020). and purified the proteins for crystallization; S.M.R., H.P., and
(2021). 91. Structures used for the analysis: CC12.1 (PDB: 6XC3), CC12.3 J.K. provided CV05-163 and other antibody clones and sequences;
71. Binding and neutralization of IGHV3-66 antibodies were also M.J.v.G., R.W.S., and D.R.B. provided plasmids for some of the
(6XC4), COVA2-04 (7JMO), B38 (7BZ5), CB6 (7C01), CV30 antibodies reported in (11, 20), respectively; M.Y. and X.Z.
abolished by K417N, as shown by (62), where IGHV3-66 (6XE1), C105 (6XCN), BD-236 (7CHB), BD-604 (7CH4), performed the crystallization and x-ray data collection and
antibody CB6, which binds to RBD in IGHV3-53/3-66 binding BD-629 (7CH5), C102 (7K8M), C1A-B3 (7KFW), C1A-C2 (7KFX), determined and refined the x-ray structures; D.H., L.P., and
mode 1 (fig. S4), was not able to bind or neutralize K417N and C1A-B12 (7KFV), C1A-F10 (7KFY), P4A1 (7CJF), P2C-1F11 D.N. performed the neutralization assays; M.Y. and C.-C.D.L.
B.1.351 or P.1. (7CDI), LY-CoV481 (7KMI), LY-CoV488 (7KM8), 910-30 carried out the binding assays; A.M.J. and A.B.W. provided nsEM
72. The epitopes have been assigned on their interaction with a (7KS9), 222 (7NX6), S2H14 (7JX3), COVA2-39 (7JMP), C144 data and performed reconstructions; M.Y., C.-C.D.L., N.C.W., and
single RBD. Quaternary epitopes are not considered in these (7K90), BD23 (7BYR), 2-4 (6XEY), CV07-250 (6XKQ), I.A.W. wrote the paper; and all authors reviewed and/or edited the
assignments. REGN10933 (6XDG), C121 (7K8X), C002 (7K8S), P2C-1A3 paper. Competing interests: Related to this work, the German
73. Although the antibodies structurally characterized to date do (7CDJ), S2E12 (7K4N), S2M11 (7K43), S2H13 (7JV2), CT-P59 Center for Neurodegenerative Diseases (DZNE) and Charité–
not represent all of the antibodies in a polyclonal response, (7CM4), LY-CoV555 (7L3N), BD-368-2 (7CHH), P2B-2F6 Universitätsmedizin Berlin previously filed a patent application that
they do represent major families of antibodies that have been (7BWJ), CV07-270 (6XKP), C104 (7K8U), P17 (7CWO), C110 included anti-SARS-CoV-2 antibody CV05-163 first reported in (17).
found in the sera of convalescent SARS-CoV-2 patients. (7K8V), C119 (7K8W), REGN10987 (6XDG), CR3022 (6W41), Data and materials availability: The x-ray coordinates and
74. We originally referred these IGHV3-53/3-66 binding modes as COVA1-16 (7JMW), EY6A (6ZDG), S304 (7JW0), S2A4 (7JVA), structure factors have been deposited to the RCSB Protein Data
“A” and “B” in (9) and (75). To distinguish from “RBS-A” and DH1047 (7LD1), S309 (6WPS), C135 (7K8Z), and CV38-142 Bank under accession code 7LOP. The EM maps have been
“RBS-B”, these IGHV3-53/3-66 binding modes are referred to (7LM8). The paratope residues of the C104 3.8-Å structure deposited in the Electron Microscopy Data Bank (EMDB) under
as “IGHV3-53/3-66 binding mode 1” and “2” in this study. that were truncated due to weak electron density were accession codes EMD-23466 (one bound), EMD-23467 (two
Likewise, IGHV1-2 antibodies approach the RBD in two binding modeled as full side chains before performing calculations. bound), and EMD-23468 (three bound). This work is licensed under
modes, which are referred as “IGHV1-2 binding mode 1” a Creative Commons Attribution 4.0 International (CC BY 4.0)
and “2”. The definitions of the binding modes in these two ACKNOWLEDGMENTS license, which permits unrestricted use, distribution, and
germline-encoded antibodies differ from “class 1” and “class 2” reproduction in any medium, provided the original work is properly
in (10), which were defined as ACE2-blocking antibodies that We thank H. Tien for technical support with the crystallization cited. To view a copy of this license, visit https://creativecommons.
bind to “up-RBD only” and to “up/down RBD”, respectively. robot, J. Matteson and Y. Hua for their contributions to mammalian org/licenses/by/4.0/. This license does not apply to figures/
75. N. C. Wu et al., Cell Rep. 33, 108274 (2020). cell culture, W. Yu for insect cell culture, and R. Stanfield for photos/artwork or other content included in the article that is
76. S. D. Boyd et al., J. Immunol. 184, 6986–6992 (2010). assistance in data collection. Funding: Supported by Bill and credited to a third party; obtain authorization from the rights holder
77. M. Rapp et al., Cell Rep. 35, 108950 (2021). Melinda Gates Foundation grants OPP1170236 and INV-004923 before using such material.
78. H. Yao et al., Cell Res. 31, 25–36 (2021). INV (I.A.W., A.B.W., and D.R.B.); NIH grants R00 AI139445 (N.C.W.),
79. RBS-C antibodies CV07-270, BD-368-2, P2B-2F6, C104, and NIH P01 AI110657 (I.A.W., A.B.W., and R.W.S.), R01 AI132317 SUPPLEMENTARY MATERIALS
P17 are encoded by IGHV3-11, IGHV3-23, IGHV4-38-2, (D.N. and D.H.), and R01 AI142945 (L.P.); German Research
IGHV4-34, and IGHV3-30, respectively. Foundation grants PR 1274/3-1 and PR 1274/5-1, Helmholtz science.sciencemag.org/content/373/6556/818/suppl/DC1
80. H. Liu et al., Immunity 53, 1272–1280.e5 (2020). Association grants HIL-A03 and SO-097, and German Federal Materials and Methods
81. H. Liu et al., Cell Host Microbe 29, 806–818.e6 (2021). Ministry of Education and Research Connect-Generate grant Figs. S1 to S12
82. K. Wu et al., bioRxiv 427948 [preprint]. 25 January 2021. 01GM1908D (H.P.); and a Vici fellowship from the Netherlands Tables S1 to S3
Organisation for Scientific Research (NWO) (R.W.S.). This research References (92–110)
83. G. B. Karlsson Hedestam et al., Nat. Rev. Microbiol. 6, 143–155 used resources of the Advanced Photon Source, a US Department MDAR Reproducibility Checklist
(2008). of Energy (DOE) Office of Science User Facility, operated for the
DOE Office of Science by Argonne National Laboratory under 17 February 2021; accepted 12 May 2021
84. B. Choi et al., N. Engl. J. Med. 383, 2291–2293 (2020). contract DE-AC02-06CH11357. Extraordinary facility operations Published online 20 May 2021
85. K. Wu et al., N. Engl. J. Med. 384, 1468–1470 (2021). were supported in part by the DOE Office of Science through the 10.1126/science.abh1139
86. Y. Liu et al., N. Engl. J. Med. 384, 1466–1468 (2021). National Virtual Biotechnology Laboratory, a consortium of DOE
87. K. R. W. Emary et al., Lancet 397, 1351–1362 (2021). national laboratories focused on the response to COVID-19, with

88. T. Moyo-Gwete et al., N. Engl. J. Med. NEJMc2104192 (2021).

SCIENCE sciencemag.org 13 AUGUST 2021 ¥ VOL 373 ISSUE 6556 823

LIFE SCIENCE TECHNOLOGIES Produced by the Science/AAAS Custom Publishing Office

new products gDNA Removal Columns

Mounting Medium -
EverBrite TrueBlack Hardset is

-

-
-

Biotium Chromatrap
3D Liver Spheroid Kit Breath Biopsy Panel for Respiratory Diseases

-
-

Corning Life Sciences -
Cryopreservation Media Owlstone Medical
Radiation-Resistant Lenses for CCTV Cameras

-
-

-
Resolve Optics

AMS Biotechnology

Electronically submit your new product description or product literature information! Go to www.sciencemag.org/about/new-products-section for more information.

Newly offered instrumentation, apparatus, and laboratory materials of interest to researchers in all disciplines in academic, industrial, and governmental organizations are featured in this
space. Emphasis is given to purpose, chief characteristics, and availability of products and materials. Endorsement by Science or AAAS of any products or materials mentioned is not
implied. Additional information may be obtained from the manufacturer or supplier.

824 13 AUGUST 2021 • VOL 373 ISSUE 6556 sciencemag.org/custom-publishing SCIENCE