Potent neutralising monoclonal antibodies targeting the spike of NL63 coronavirus
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.
Authors
- P. Mark Hogarth (ORCID: https://orcid.org/0000-0002-0360-7890)
- Adam K. Wheatley (ORCID: https://orcid.org/0000-0002-5593-9387)
- Robyn Esterbauer (ORCID: https://orcid.org/0000-0002-7091-0048)
- Thomas Tran (ORCID: https://orcid.org/0000-0001-7931-0164)
- Lara S. U. Schwab
- George Taiaroa (ORCID: https://orcid.org/0009-0009-3050-1424)
- Monique L. Smith (ORCID: https://orcid.org/0000-0002-2656-0677)
- Matthew J. Gartner (ORCID: https://orcid.org/0000-0003-4953-9501)
- Meghan Conlan
- Jennifer A. Juno (ORCID: https://orcid.org/0000-0002-9072-1017)
- Stephen John Kent (ORCID: https://orcid.org/0000-0002-8539-4891)
- Ellie Reilly
- Hyon‐Xhi Tan (ORCID: https://orcid.org/0000-0003-1064-3934)
- Bruce D. Wines (ORCID: https://orcid.org/0000-0002-4108-375X)
- Thakshila H. Amarasena (ORCID: https://orcid.org/0000-0003-4685-4127)
- Wen Shi Lee (ORCID: https://orcid.org/0000-0001-7285-4054)
- Kanta Subbarao (ORCID: https://orcid.org/0000-0003-1713-3056)
- Phillip Pymm (ORCID: https://orcid.org/0000-0003-2722-4621)
- Jessica A. Neil
- Mingyang Wang (ORCID: https://orcid.org/0000-0001-7201-5090)
- Rory A. Shepherd (ORCID: https://orcid.org/0009-0001-2215-2510)
- Andrew P. Kelly (ORCID: https://orcid.org/0000-0003-2719-6544)
Institutions
- The Royal Melbourne Hospital (AU)
- Burnet Institute (AU)
- The University of Melbourne (AU)
- Walter and Eliza Hall Institute of Medical Research (AU)
- Victorian Infectious Diseases Reference Laboratory (AU)
- Centre hospitalier universitaire de Québec (CA)
- Melbourne Sexual Health Centre (AU)
- Peter Doherty Institute (AU)
- Centre hospitalier de l'Université Laval (CA)
- Université Laval (CA)
- Monash University (AU)
Publication Details
- Journal
- npj Viruses
- Published
- 2025-04-25
- DOI
- https://doi.org/10.1038/s44298-025-00116-x
- Citations
- 2
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 2.79
Funders
- Medical Research Council
- National Health and Medical Research Council