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A panel of nanobodies recognizing conserved hidden clefts of all SARS-CoV-2 spike variants including Omicron.

ABSTRACT: We are amid the historic coronavirus infectious disease 2019 (COVID-19) pandemic. Imbalances in the accessibility of vaccines, medicines, and diagnostics among countries, regions, and populations, and those in war crises, have been problematic. Nanobodies are small, stable, customizable, and inexpensive to produce. Herein, we present a panel of nanobodies that can detect the spike proteins of five SARS-CoV-2 variants of concern (VOCs) including Omicron. Here we show via ELISA, lateral flow, kinetic, flow cytometric, microscopy, and Western blotting assays that our nanobodies can quantify the spike variants. This panel of nanobodies broadly neutralizes viral infection caused by pseudotyped and authentic SARS-CoV-2 VOCs. Structural analyses show that the P86 clone targets epitopes that are conserved yet unclassified on the receptor-binding domain (RBD) and contacts the N-terminal domain (NTD). Human antibodies rarely access both regions; consequently, the clone buries hidden crevasses of SARS-CoV-2 spike proteins that go undetected by conventional antibodies.

SUBMITTER: Maeda R

PROVIDER: S-EPMC9257560 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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A panel of nanobodies recognizing conserved hidden clefts of all SARS-CoV-2 spike variants including Omicron.

Maeda Ryota R Fujita Junso J Konishi Yoshinobu Y Kazuma Yasuhiro Y Yamazaki Hiroyuki H Anzai Itsuki I Watanabe Tokiko T Yamaguchi Keishi K Kasai Kazuki K Nagata Kayoko K Yamaoka Yutaro Y Miyakawa Kei K Ryo Akihide A Shirakawa Kotaro K Sato Kei K Makino Fumiaki F Matsuura Yoshiharu Y Inoue Tsuyoshi T Imura Akihiro A Namba Keiichi K Takaori-Kondo Akifumi A

Communications biology 20220706 1

We are amid the historic coronavirus infectious disease 2019 (COVID-19) pandemic. Imbalances in the accessibility of vaccines, medicines, and diagnostics among countries, regions, and populations, and those in war crises, have been problematic. Nanobodies are small, stable, customizable, and inexpensive to produce. Herein, we present a panel of nanobodies that can detect the spike proteins of five SARS-CoV-2 variants of concern (VOCs) including Omicron. Here we show via ELISA, lateral flow, kine ...[more]

PMID: 35794202

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Project description:BackgroundSARS-CoV-2 transmission in India in 2020-2022 was driven predominantly by Wild (Wuhan-Hu-1and D614G), Delta, and Omicron variants. The aim of this study was to examine the effect of infections on the humoral immune response and cross-reactivity to spike proteins of Wuhan-Hu-1, Delta, C.1.2., and Omicron.ObjectivesResidual archival sera (N=81) received between January 2020 and March 2022 were included. Infection status was inferred by a positive SARS-CoV-2 RT-PCR and/or serology (anti-N and anti-S antibodies) and sequencing of contemporaneous samples (N=18) to infer lineage. We estimated the levels and cross-reactivity of infection-induced sera including Wild, Delta, Omicron as well as vaccine breakthrough infections (Delta and Omicron).ResultsWe found ~2-fold increase in spike-specific IgG antibody binding in post-Omicron infection compared to the pre-Omicron period, whilst the change in pre- and post-Delta infections were similar. Further investigation of Omicron-specific humoral responses revealed primary Omicron infection as an inducer of cross-reactive antibodies against predecessor variants, in spite of weaker degree of humoral response compared to Wuhan-Hu-1 and Delta infection. Intriguingly, Omicron vaccine-breakthrough infections when compared with primary infections, exhibited increased humoral responses against RBD (7.7-fold) and Trimeric S (Trimeric form of spike protein) (34.6-fold) in addition to increased binding of IgGs towards previously circulating variants (4.2 - 6.5-fold). Despite Delta breakthrough infections showing a higher level of humoral response against RBD (2.9-fold) and Trimeric S (5.7-fold) compared to primary Delta sera, a demonstrably reduced binding (36-49%) was observed to Omicron spike protein.ConclusionsOmicron vaccine breakthrough infection results in increased intensity of humoral response and wider breadth of IgG binding to spike proteins of antigenically-distinct, predecessor variants. This article is protected by copyright. All rights reserved.

Dataset Information

A panel of nanobodies recognizing conserved hidden clefts of all SARS-CoV-2 spike variants including Omicron.

Publications

A panel of nanobodies recognizing conserved hidden clefts of all SARS-CoV-2 spike variants including Omicron.

Similar Datasets

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