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<p>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.</p>

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Potent neutralising monoclonal antibodies targeting the spike of NL63 coronavirus

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年4月25日

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  • 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

摘要

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.