Immunizations with diverse sarbecovirus receptor binding domains elicit SARS-CoV-2 neutralizing antibodies against a conserved site of vulnerability
Field | Value | Language |
dc.contributor.author | Burnett, Deborah L | en_AU |
dc.contributor.author | Jackson, Katherine J L | en_AU |
dc.contributor.author | Langley, David B | en_AU |
dc.contributor.author | Aggrawal, Anupria | en_AU |
dc.contributor.author | Stella, Alberto Ospina | en_AU |
dc.contributor.author | Johansen, Matt D | en_AU |
dc.contributor.author | Balachandran, Harikrishnan | en_AU |
dc.contributor.author | Lenthall, Helen | en_AU |
dc.contributor.author | Rouet, Romain | en_AU |
dc.contributor.author | Walker, Gregory | en_AU |
dc.contributor.author | Saunders, Bernadette M | en_AU |
dc.contributor.author | Singh, Mandeep | en_AU |
dc.contributor.author | Li, Hui | en_AU |
dc.contributor.author | Henry, Jake Y | en_AU |
dc.contributor.author | Jackson, Jennifer | en_AU |
dc.contributor.author | Stewart, Alastair G | en_AU |
dc.contributor.author | Witthauer, Franka | en_AU |
dc.contributor.author | Spence, Matthew A | en_AU |
dc.contributor.author | Hansbro, Nicole G | en_AU |
dc.contributor.author | Jackson, Colin | en_AU |
dc.contributor.author | Schofield, Peter | en_AU |
dc.contributor.author | Milthorpe, Claire | en_AU |
dc.contributor.author | Martinello, Marianne | en_AU |
dc.contributor.author | Schulz, Sebastian R | en_AU |
dc.contributor.author | Roth, Edith | en_AU |
dc.contributor.author | Kelleher, Anthony | en_AU |
dc.contributor.author | Emery, Sean | en_AU |
dc.contributor.author | Britton, Warwick J | en_AU |
dc.contributor.author | Rawlinson, William D | en_AU |
dc.contributor.author | Karl, Rudolfo | en_AU |
dc.contributor.author | Schäfer, Simon | en_AU |
dc.contributor.author | Winkler, Thomas H | en_AU |
dc.contributor.author | Brink, Robert | en_AU |
dc.contributor.author | Bull, Rowena A | en_AU |
dc.contributor.author | Hansbro, Philip M | en_AU |
dc.contributor.author | Jäck, Hans-Martin | en_AU |
dc.contributor.author | Turville, Stuart | en_AU |
dc.contributor.author | Christ, Daniel | en_AU |
dc.contributor.author | Goodnow, Christopher C | en_AU |
dc.date.accessioned | 2021-11-26T05:05:01Z | |
dc.date.available | 2021-11-26T05:05:01Z | |
dc.date.issued | 2021 | |
dc.identifier.uri | https://hdl.handle.net/2123/26997 | |
dc.description.abstract | Viral mutations are an emerging concern in reducing SARS-CoV-2 vaccination efficacy. Second-generation vaccines will need to elicit neutralizing antibodies against sites that are evolutionarily conserved across the sarbecovirus subgenus. Here, we immunized mice containing a human antibody repertoire with diverse sarbecovirus receptor-binding domains (RBDs) to identify antibodies targeting conserved sites of vulnerability. Antibodies with broad reactivity against diverse clade B RBDs targeting the conserved class 4 epitope, with recurring IGHV/IGKV pairs, were readily elicited but were non-neutralizing. However, rare class 4 antibodies binding this conserved RBD supersite showed potent neutralization of SARS-CoV-2 and all variants of concern. Structural analysis revealed that the neutralizing ability of cross-reactive antibodies was reserved only for those with an elongated CDRH3 that extends the antiparallel beta-sheet RBD core and orients the antibody light chain to obstruct ACE2-RBD interactions. These results identify a structurally defined pathway for vaccine strategies eliciting escape-resistant SARS-CoV-2 neutralizing antibodies. | en_AU |
dc.language.iso | en | en_AU |
dc.subject | COVID-19 | en_AUI |
dc.subject | Coronavirus | en_AUI |
dc.title | Immunizations with diverse sarbecovirus receptor binding domains elicit SARS-CoV-2 neutralizing antibodies against a conserved site of vulnerability | en_AU |
dc.type | Article | en_AU |
dc.identifier.doi | 10.1016/j.immuni.2021.10.019 |
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