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

Youri Lee, Laura Klenow, Elizabeth M. Coyle, Gabrielle Grubbs, Hana Golding and Surender Khurana ()
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Youri Lee: Center for Biologics Evaluation and Research (CBER), FDA
Laura Klenow: Center for Biologics Evaluation and Research (CBER), FDA
Elizabeth M. Coyle: Center for Biologics Evaluation and Research (CBER), FDA
Gabrielle Grubbs: Center for Biologics Evaluation and Research (CBER), FDA
Hana Golding: Center for Biologics Evaluation and Research (CBER), FDA
Surender Khurana: Center for Biologics Evaluation and Research (CBER), FDA

Nature Communications, 2024, vol. 15, issue 1, 1-11

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-47146-2

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