Potent neutralising monoclonal antibodies targeting the spike of NL63 coronavirus
Abstract NL63 is an alphacoronavirus that uses the same ACE2 receptor as SARS-CoV and SARS-CoV-2, but generally causes mild respiratory illness. In a cohort of healthy adults, we characterised humoral responses against NL63 spike and isolated a panel of human monoclonal antibodies (mAbs), including...
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Nature Portfolio
2025-04-01
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| Series: | npj Viruses |
| Online Access: | https://doi.org/10.1038/s44298-025-00116-x |
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| author | Wen Shi Lee George Taiaroa Robyn Esterbauer Meghan Conlan Jessica A. Neil Matthew J. Gartner Monique Smith Mingyang Wang Rory A. Shepherd Thomas Tran Phillip Pymm Lara S. U. Schwab Andrew Kelly Ellie Reilly Thakshila Amarasena Bruce D. Wines P. Mark Hogarth Jennifer A. Juno Stephen J. Kent Hyon-Xhi Tan Kanta Subbarao Adam K. Wheatley |
| author_facet | Wen Shi Lee George Taiaroa Robyn Esterbauer Meghan Conlan Jessica A. Neil Matthew J. Gartner Monique Smith Mingyang Wang Rory A. Shepherd Thomas Tran Phillip Pymm Lara S. U. Schwab Andrew Kelly Ellie Reilly Thakshila Amarasena Bruce D. Wines P. Mark Hogarth Jennifer A. Juno Stephen J. Kent Hyon-Xhi Tan Kanta Subbarao Adam K. Wheatley |
| author_sort | Wen Shi Lee |
| collection | DOAJ |
| description | Abstract NL63 is an alphacoronavirus that uses the same ACE2 receptor as SARS-CoV and SARS-CoV-2, but generally causes mild respiratory illness. In a cohort of healthy adults, we characterised humoral responses against NL63 spike and isolated a panel of human monoclonal antibodies (mAbs), including five with potent viral neutralising activity. Four neutralising mAbs blocked ACE2 receptor engagement and were found to target the receptor binding motif. A single mAb targeting the S2 subunit displayed potent neutralisation activity comparable to those directly blocking receptor engagement. The S2 mAb targets a membrane proximal heptad repeat 2 (HR2) region in spike that is absent in betacoronaviruses, potentially revealing a site of vulnerability unique to alphacoronaviruses. For all neutralising mAbs, putative epitopes were highly conserved in over 200 NL63 sequences, including recent clinical isolates. A deeper understanding of the recognition of alphacoronavirus spike by human antibodies will guide vaccine and therapeutic development against alphacoronavirus threats. |
| format | Article |
| id | doaj-art-3b0cfe57128e47a6a2fb24656b7aadaf |
| institution | DOAJ |
| issn | 2948-1767 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Viruses |
| spelling | doaj-art-3b0cfe57128e47a6a2fb24656b7aadaf2025-08-20T03:14:07ZengNature Portfolionpj Viruses2948-17672025-04-013111010.1038/s44298-025-00116-xPotent neutralising monoclonal antibodies targeting the spike of NL63 coronavirusWen Shi Lee0George Taiaroa1Robyn Esterbauer2Meghan Conlan3Jessica A. Neil4Matthew J. Gartner5Monique Smith6Mingyang Wang7Rory A. Shepherd8Thomas Tran9Phillip Pymm10Lara S. U. Schwab11Andrew Kelly12Ellie Reilly13Thakshila Amarasena14Bruce D. Wines15P. Mark Hogarth16Jennifer A. Juno17Stephen J. Kent18Hyon-Xhi Tan19Kanta Subbarao20Adam K. Wheatley21Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of MelbourneVictorian Infectious Diseases Reference Laboratory, The Royal Melbourne Hospital at The Peter Doherty Institute for Infection and ImmunityDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of MelbourneDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of MelbourneDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of MelbourneDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of MelbourneDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of MelbourneDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of MelbourneDepartment of Infectious Diseases, Peter Doherty Institute for Infection and Immunity, University of MelbourneVictorian Infectious Diseases Reference Laboratory, The Royal Melbourne Hospital at The Peter Doherty Institute for Infection and ImmunityDivision of Infection and Global Health, Walter and Eliza Hall InstituteDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of MelbourneDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of MelbourneDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of MelbourneDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of MelbourneBurnet InstituteBurnet InstituteDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of MelbourneDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of MelbourneDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of MelbourneDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of MelbourneDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of MelbourneAbstract NL63 is an alphacoronavirus that uses the same ACE2 receptor as SARS-CoV and SARS-CoV-2, but generally causes mild respiratory illness. In a cohort of healthy adults, we characterised humoral responses against NL63 spike and isolated a panel of human monoclonal antibodies (mAbs), including five with potent viral neutralising activity. Four neutralising mAbs blocked ACE2 receptor engagement and were found to target the receptor binding motif. A single mAb targeting the S2 subunit displayed potent neutralisation activity comparable to those directly blocking receptor engagement. The S2 mAb targets a membrane proximal heptad repeat 2 (HR2) region in spike that is absent in betacoronaviruses, potentially revealing a site of vulnerability unique to alphacoronaviruses. For all neutralising mAbs, putative epitopes were highly conserved in over 200 NL63 sequences, including recent clinical isolates. A deeper understanding of the recognition of alphacoronavirus spike by human antibodies will guide vaccine and therapeutic development against alphacoronavirus threats.https://doi.org/10.1038/s44298-025-00116-x |
| spellingShingle | Wen Shi Lee George Taiaroa Robyn Esterbauer Meghan Conlan Jessica A. Neil Matthew J. Gartner Monique Smith Mingyang Wang Rory A. Shepherd Thomas Tran Phillip Pymm Lara S. U. Schwab Andrew Kelly Ellie Reilly Thakshila Amarasena Bruce D. Wines P. Mark Hogarth Jennifer A. Juno Stephen J. Kent Hyon-Xhi Tan Kanta Subbarao Adam K. Wheatley Potent neutralising monoclonal antibodies targeting the spike of NL63 coronavirus npj Viruses |
| title | Potent neutralising monoclonal antibodies targeting the spike of NL63 coronavirus |
| title_full | Potent neutralising monoclonal antibodies targeting the spike of NL63 coronavirus |
| title_fullStr | Potent neutralising monoclonal antibodies targeting the spike of NL63 coronavirus |
| title_full_unstemmed | Potent neutralising monoclonal antibodies targeting the spike of NL63 coronavirus |
| title_short | Potent neutralising monoclonal antibodies targeting the spike of NL63 coronavirus |
| title_sort | potent neutralising monoclonal antibodies targeting the spike of nl63 coronavirus |
| url | https://doi.org/10.1038/s44298-025-00116-x |
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