Superimmunity by pan-sarbecovirus nanobodies

Yufei 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

doi:https://doi.org/10.1016/j.celrep.2022.111004

Superimmunity by pan-sarbecovirus nanobodies

Yufei 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

Tel Aviv University, The Hebrew University of Jerusalem

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Article number	111004
Journal	Cell Reports
Volume	39
Issue number	13
DOIs	https://doi.org/10.1016/j.celrep.2022.111004
State	Published - 28 Jun 2022

Keywords

CP: Immunology
SARS-CoV-2
VH antibody
broadly neutralizing nanobody
inhalable bispecific nanobody PiN-31
pan-sarbecovirus neutralization
super immunity

All Science Journal Classification (ASJC) codes

General Biochemistry,Genetics and Molecular Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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https://doi.org/10.1016/j.celrep.2022.111004

Cite this

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title = "Superimmunity by pan-sarbecovirus nanobodies",

abstract = "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.",

keywords = "CP: Immunology, SARS-CoV-2, VH antibody, broadly neutralizing nanobody, inhalable bispecific nanobody PiN-31, pan-sarbecovirus neutralization, super immunity",

author = "Yufei Xiang and Wei Huang and Hejun Liu and Zhe Sang and Sham Nambulli and J{\'e}r{\^o}me Tubiana and Williams, {Kevin L.} and Duprex, {W. Paul} and Dina Schneidman-Duhovny and Wilson, {Ian A.} and Taylor, {Derek J.} and Yi Shi",

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T1 - Superimmunity by pan-sarbecovirus nanobodies

AU - Xiang, Yufei

AU - Huang, Wei

AU - Liu, Hejun

AU - Sang, Zhe

AU - Nambulli, Sham

AU - Tubiana, Jérôme

AU - Williams, Kevin L.

AU - Duprex, W. Paul

AU - Schneidman-Duhovny, Dina

AU - Wilson, Ian A.

AU - Taylor, Derek J.

AU - Shi, Yi

PY - 2022/6/28

Y1 - 2022/6/28

N2 - 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.

AB - 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.

KW - CP: Immunology

KW - SARS-CoV-2

KW - VH antibody

KW - broadly neutralizing nanobody

KW - inhalable bispecific nanobody PiN-31

KW - pan-sarbecovirus neutralization

KW - super immunity

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Superimmunity by pan-sarbecovirus nanobodies

Abstract

Keywords

All Science Journal Classification (ASJC) codes

UN SDGs

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