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...
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Nature Portfolio
2024-04-01
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Series: | Nature Communications |
Online Access: | https://doi.org/10.1038/s41467-024-47146-2 |
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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. |
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issn | 2041-1723 |
language | English |
last_indexed | 2024-04-24T12:38:40Z |
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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 |
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