Potent neutralising monoclonal antibodies targeting the spike of NL63 coronavirus

Potent neutralising monoclonal antibodies targeting the spike of NL63 coronavirus

Blog Article

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 Admin Fee 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 Boot Box 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.