Monoclonal antibodies targeting sites in respiratory syncytial virus attachment G protein provide protection against RSV-A and RSV-B in mice

Abstract Currently, only Palivizumab and Nirsevimab that target the respiratory syncytical virus (RSV) fusion protein are licensed for pre-treatment of infants. Glycoprotein-targeting antibodies may also provide protection against RSV. In this study, we generate monoclonal antibodies from mice immun...

Full description

Bibliographic Details
Main Authors: Youri Lee, Laura Klenow, Elizabeth M. Coyle, Gabrielle Grubbs, Hana Golding, Surender Khurana
Format: Article
Language:English
Published: Nature Portfolio 2024-04-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-024-47146-2
_version_ 1797219753719234560
author Youri Lee
Laura Klenow
Elizabeth M. Coyle
Gabrielle Grubbs
Hana Golding
Surender Khurana
author_facet Youri Lee
Laura Klenow
Elizabeth M. Coyle
Gabrielle Grubbs
Hana Golding
Surender Khurana
author_sort Youri Lee
collection DOAJ
description Abstract Currently, only Palivizumab and Nirsevimab that target the respiratory syncytical virus (RSV) fusion protein are licensed for pre-treatment of infants. Glycoprotein-targeting antibodies may also provide protection against RSV. In this study, we generate monoclonal antibodies from mice immunized with G proteins from RSV-A2 and RSV-B1 strains. These monoclonal antibodies recognize six unique antigenic classes (G0-G5). None of the anti-G monoclonal antibodies neutralize RSV-A2 or RSV-B1 in vitro. In mice challenged with either RSV-A2 line 19 F or RSV-B1, one day after treatment with anti-G monoclonal antibodies, all monoclonal antibodies reduce lung pathology and significantly reduce lung infectious viral titers by more than 2 logs on day 5 post-RSV challenge. RSV dissemination in the lungs was variable and correlated with lung pathology. We demonstrate new cross-protective anti-G monoclonal antibodies targeting multiple sites including conformation-dependent class G0 MAb 77D2, CCD-specific class G1 MAb 40D8, and carboxy terminus of CCD class G5 MAb 7H11, to support development of G-targeting monoclonal antibodies against RSV.
first_indexed 2024-04-24T12:38:40Z
format Article
id doaj.art-b2e10af17bb8459ea84238f56db68125
institution Directory Open Access Journal
issn 2041-1723
language English
last_indexed 2024-04-24T12:38:40Z
publishDate 2024-04-01
publisher Nature Portfolio
record_format Article
series Nature Communications
spelling doaj.art-b2e10af17bb8459ea84238f56db681252024-04-07T11:24:14ZengNature PortfolioNature Communications2041-17232024-04-0115111110.1038/s41467-024-47146-2Monoclonal antibodies targeting sites in respiratory syncytial virus attachment G protein provide protection against RSV-A and RSV-B in miceYouri Lee0Laura Klenow1Elizabeth M. Coyle2Gabrielle Grubbs3Hana Golding4Surender Khurana5Division of Viral Products, Center for Biologics Evaluation and Research (CBER), FDADivision of Viral Products, Center for Biologics Evaluation and Research (CBER), FDADivision of Viral Products, Center for Biologics Evaluation and Research (CBER), FDADivision of Viral Products, Center for Biologics Evaluation and Research (CBER), FDADivision of Viral Products, Center for Biologics Evaluation and Research (CBER), FDADivision of Viral Products, Center for Biologics Evaluation and Research (CBER), FDAAbstract Currently, only Palivizumab and Nirsevimab that target the respiratory syncytical virus (RSV) fusion protein are licensed for pre-treatment of infants. Glycoprotein-targeting antibodies may also provide protection against RSV. In this study, we generate monoclonal antibodies from mice immunized with G proteins from RSV-A2 and RSV-B1 strains. These monoclonal antibodies recognize six unique antigenic classes (G0-G5). None of the anti-G monoclonal antibodies neutralize RSV-A2 or RSV-B1 in vitro. In mice challenged with either RSV-A2 line 19 F or RSV-B1, one day after treatment with anti-G monoclonal antibodies, all monoclonal antibodies reduce lung pathology and significantly reduce lung infectious viral titers by more than 2 logs on day 5 post-RSV challenge. RSV dissemination in the lungs was variable and correlated with lung pathology. We demonstrate new cross-protective anti-G monoclonal antibodies targeting multiple sites including conformation-dependent class G0 MAb 77D2, CCD-specific class G1 MAb 40D8, and carboxy terminus of CCD class G5 MAb 7H11, to support development of G-targeting monoclonal antibodies against RSV.https://doi.org/10.1038/s41467-024-47146-2
spellingShingle Youri Lee
Laura Klenow
Elizabeth M. Coyle
Gabrielle Grubbs
Hana Golding
Surender Khurana
Monoclonal antibodies targeting sites in respiratory syncytial virus attachment G protein provide protection against RSV-A and RSV-B in mice
Nature Communications
title Monoclonal antibodies targeting sites in respiratory syncytial virus attachment G protein provide protection against RSV-A and RSV-B in mice
title_full Monoclonal antibodies targeting sites in respiratory syncytial virus attachment G protein provide protection against RSV-A and RSV-B in mice
title_fullStr Monoclonal antibodies targeting sites in respiratory syncytial virus attachment G protein provide protection against RSV-A and RSV-B in mice
title_full_unstemmed Monoclonal antibodies targeting sites in respiratory syncytial virus attachment G protein provide protection against RSV-A and RSV-B in mice
title_short Monoclonal antibodies targeting sites in respiratory syncytial virus attachment G protein provide protection against RSV-A and RSV-B in mice
title_sort monoclonal antibodies targeting sites in respiratory syncytial virus attachment g protein provide protection against rsv a and rsv b in mice
url https://doi.org/10.1038/s41467-024-47146-2
work_keys_str_mv AT yourilee monoclonalantibodiestargetingsitesinrespiratorysyncytialvirusattachmentgproteinprovideprotectionagainstrsvaandrsvbinmice
AT lauraklenow monoclonalantibodiestargetingsitesinrespiratorysyncytialvirusattachmentgproteinprovideprotectionagainstrsvaandrsvbinmice
AT elizabethmcoyle monoclonalantibodiestargetingsitesinrespiratorysyncytialvirusattachmentgproteinprovideprotectionagainstrsvaandrsvbinmice
AT gabriellegrubbs monoclonalantibodiestargetingsitesinrespiratorysyncytialvirusattachmentgproteinprovideprotectionagainstrsvaandrsvbinmice
AT hanagolding monoclonalantibodiestargetingsitesinrespiratorysyncytialvirusattachmentgproteinprovideprotectionagainstrsvaandrsvbinmice
AT surenderkhurana monoclonalantibodiestargetingsitesinrespiratorysyncytialvirusattachmentgproteinprovideprotectionagainstrsvaandrsvbinmice