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TitleSuperimmunity by pan-sarbecovirus nanobodies.
Journal, issue, pagesCell Rep, Vol. 39, Issue 13, Page 111004, Year 2022
Publish dateJun 28, 2022
AuthorsYufei Xiang / Wei Huang / Hejun Liu / Zhe Sang / Sham Nambulli / Jérôme Tubiana / Kevin L Williams / W Paul Duprex / Dina Schneidman-Duhovny / Ian A Wilson / Derek J Taylor / Yi Shi /
PubMed AbstractVaccine boosters and infection can facilitate the development of SARS-CoV-2 antibodies with improved potency and breadth. Here, we observe superimmunity in a camelid extensively immunized with the ...Vaccine boosters and infection can facilitate the development of SARS-CoV-2 antibodies with improved potency and breadth. Here, we observe superimmunity in a camelid extensively immunized with the SARS-CoV-2 receptor-binding domain (RBD). We rapidly isolate a large repertoire of specific ultra-high-affinity nanobodies that bind strongly to all known sarbecovirus clades using integrative proteomics. These pan-sarbecovirus nanobodies (psNbs) are highly effective against SARS-CoV and SARS-CoV-2 variants, including Omicron, with the best median neutralization potency at single-digit nanograms per milliliter. A highly potent, inhalable, and bispecific psNb (PiN-31) is also developed. Structural determinations of 13 psNbs with the SARS-CoV-2 spike or RBD reveal five epitope classes, providing insights into the mechanisms and evolution of their broad activities. The highly evolved psNbs target small, flat, and flexible epitopes that contain over 75% of conserved RBD surface residues. Their potencies are strongly and negatively correlated with the distance of the epitopes from the receptor binding sites.
External linksCell Rep / PubMed:35738279 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution1.71 - 3.6 Å
Structure data

27061

8cxn

EMDB-27061, PDB-8cxn:
SARS-CoV-2 Spike protein in complex with a pan-sarbecovirus nanobody 2-57
Method: EM (single particle) / Resolution: 2.9 Å

27067

8cxq

EMDB-27067, PDB-8cxq:
SARS-CoV-2 Spike protein in complex with a pan-sarbecovirus nanobody 1-22
Method: EM (single particle) / Resolution: 2.3 Å

27068

8cy6

EMDB-27068, PDB-8cy6:
SARS-CoV-2 Spike protein in complex with a pan-sarbecovirus nanobody 2-65
Method: EM (single particle) / Resolution: 3.2 Å

27069

8cy7

EMDB-27069, PDB-8cy7:
SARS-CoV-2 Spike protein in complex with a pan-sarbecovirus nanobody 2-34
Method: EM (single particle) / Resolution: 2.9 Å

27071

8cy9

EMDB-27071, PDB-8cy9:
SARS-CoV-2 Spike protein in complex with a pan-sarbecovirus nanobody 1-23
Method: EM (single particle) / Resolution: 2.9 Å

27072

8cya

EMDB-27072, PDB-8cya:
SARS-CoV-2 Spike protein in complex with a pan-sarbecovirus nanobody 2-67
Method: EM (single particle) / Resolution: 2.7 Å

27073

8cyb

EMDB-27073, PDB-8cyb:
SARS-CoV-2 Spike protein in complex with a pan-sarbecovirus nanobody 1-8
Method: EM (single particle) / Resolution: 2.7 Å

27074

8cyc

EMDB-27074, PDB-8cyc:
SARS-CoV-2 Spike protein in complex with a pan-sarbecovirus nanobody 2-34
Method: EM (single particle) / Resolution: 2.9 Å

27075

8cyd

EMDB-27075, PDB-8cyd:
SARS-CoV-2 Spike protein in complex with a pan-sarbecovirus nanobody 2-45
Method: EM (single particle) / Resolution: 2.6 Å

27080

8cyj

EMDB-27080, PDB-8cyj:
RBD of SARS-CoV-2 Spike protein in complex with pan-sarbecovirus nanobodies 2-10, 2-67, 2-62 and 1-25
Method: EM (single particle) / Resolution: 3.6 Å

PDB-8cwu:
Crystal structure of SARS-CoV-2 spike protein receptor-binding domain in complex with a cross-neutralizing nanobody 1-21
Method: X-RAY DIFFRACTION / Resolution: 1.71 Å

PDB-8cwv:
Crystal structure of SARS-CoV-2 spike protein receptor-binding domain in complex with a cross-neutralizing nanobody 2-31 and a human antibody CC12.1 Fab
Method: X-RAY DIFFRACTION / Resolution: 2.51 Å

Chemicals

ChemComp-HOH:
WATER

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-AH2:
1-deoxy-alpha-D-mannopyranose

Source
  • lama glama (llama)
  • severe acute respiratory syndrome coronavirus 2
  • homo sapiens (human)
KeywordsIMMUNE SYSTEM / cross-neutralizing antibody; nanobody; SARS-CoV-2; Sarbecovirus; IMMUNE SYSTEM; VHH / cross-neutralizing antibody; nanobody; SARS-CoV-2; Sarbecovirus; IMMUNE SYSTEM; VHH; CC12.1 / VIRAL PROTEIN / SARS-CoV-2 / Spike protein / nanobody / broad binding

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