Evidence map›Paper›PMID 34788600›Full record

ArticleImmunity2021

Immunizations with diverse sarbecovirus receptor-binding domains elicit SARS-CoV-2 neutralizing antibodies against a conserved site of vulnerability.

Deborah L Burnett, Katherine J L Jackson, David B Langley, Anupria Aggrawal, Alberto Ospina Stella, Matt D Johansen, Harikrishnan Balachandran, Helen Lenthall, Romain Rouet, Gregory Walker and 29 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Immunity, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
3.1field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

40 citing papers in PubMed, 54 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Cross-reactive sarbecovirus antibodies induced by mosaic RBD nanoparticles.Proceedings of the National Academy of Sciences of the United States of America · 2025
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  8. Affinity maturation endows potent activity onto class 6 SARS-CoV-2 broadly neutralizing antibodies.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  9. Upper respiratory tract immunization with PamFrontiers in immunology · 2025
    Article
  10. Review
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  15. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

39 authors at 9 institutions in 2 countries.

Deborah L BurnettGarvan Institute of Medical Research, Sydney, NSW 2010, Australia; UNSW Sydney, Faculty of Medicine, Sydney, NSW 2010, Australia. Electronic address: d.burnett@garvan.org.au.
Katherine J L JacksonGarvan Institute of Medical Research, Sydney, NSW 2010, Australia.
David B LangleyGarvan Institute of Medical Research, Sydney, NSW 2010, Australia.
Anupria AggrawalKirby Institute, UNSW, Sydney, NSW 2052, Australia.
Alberto Ospina StellaKirby Institute, UNSW, Sydney, NSW 2052, Australia.
Matt D JohansenCenter for Inflammation, Centenary Institute and University of Technology Sydney, Faculty of Science, School of Life Sciences, Sydney, NSW 2006, Australia.
Harikrishnan BalachandranKirby Institute, UNSW, Sydney, NSW 2052, Australia.
Helen LenthallGarvan Institute of Medical Research, Sydney, NSW 2010, Australia.
Romain RouetGarvan Institute of Medical Research, Sydney, NSW 2010, Australia; UNSW Sydney, Faculty of Medicine, Sydney, NSW 2010, Australia.
Gregory WalkerUNSW Sydney, Faculty of Medicine, Sydney, NSW 2010, Australia.
Bernadette M SaundersCenter for Inflammation, Centenary Institute and University of Technology Sydney, Faculty of Science, School of Life Sciences, Sydney, NSW 2006, Australia.
Mandeep SinghGarvan Institute of Medical Research, Sydney, NSW 2010, Australia; UNSW Sydney, Faculty of Medicine, Sydney, NSW 2010, Australia.
Hui LiKirby Institute, UNSW, Sydney, NSW 2052, Australia.
Jake Y HenryGarvan Institute of Medical Research, Sydney, NSW 2010, Australia.
Jennifer JacksonGarvan Institute of Medical Research, Sydney, NSW 2010, Australia.
Alastair G StewartUNSW Sydney, Faculty of Medicine, Sydney, NSW 2010, Australia; Victor Chang Cardiac Research Institute, Sydney, NSW 2010, Australia.
Franka WitthauerDivision of Molecular Immunology, University Hospital Erlangen, University of Erlangen-Nürnberg, Erlangen 91054, Germany.
Matthew A SpenceResearch School of Chemistry, Australian National University, Canberra, ACT 2601, Australia.
Nicole G HansbroCenter for Inflammation, Centenary Institute and University of Technology Sydney, Faculty of Science, School of Life Sciences, Sydney, NSW 2006, Australia.
Colin JacksonResearch School of Chemistry, Australian National University, Canberra, ACT 2601, Australia.
Peter SchofieldGarvan Institute of Medical Research, Sydney, NSW 2010, Australia; UNSW Sydney, Faculty of Medicine, Sydney, NSW 2010, Australia.
Claire MilthorpeGarvan Institute of Medical Research, Sydney, NSW 2010, Australia.
Marianne MartinelloKirby Institute, UNSW, Sydney, NSW 2052, Australia.
Sebastian R SchulzDivision of Molecular Immunology, University Hospital Erlangen, University of Erlangen-Nürnberg, Erlangen 91054, Germany.
Edith RothDivision of Molecular Immunology, University Hospital Erlangen, University of Erlangen-Nürnberg, Erlangen 91054, Germany.
Anthony KelleherKirby Institute, UNSW, Sydney, NSW 2052, Australia.
Sean EmeryKirby Institute, UNSW, Sydney, NSW 2052, Australia.
Warwick J BrittonCentenary Institute, The University of Sydney, Sydney, NSW 2006, Australia.
William D RawlinsonUNSW Sydney, Faculty of Medicine, Sydney, NSW 2010, Australia; Serology and Virology Division (SAViD), NSW Health Pathology, SEALS Randwick, Sydney, NSW 2031, Australia.
Rudolfo KarlDivision of Genetics, Department Biology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen 91054, Germany.
Simon SchäferDivision of Genetics, Department Biology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen 91054, Germany.
Thomas H WinklerDivision of Genetics, Department Biology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen 91054, Germany.
Robert BrinkGarvan Institute of Medical Research, Sydney, NSW 2010, Australia; UNSW Sydney, Faculty of Medicine, Sydney, NSW 2010, Australia.
Rowena A BullUNSW Sydney, Faculty of Medicine, Sydney, NSW 2010, Australia; Kirby Institute, UNSW, Sydney, NSW 2052, Australia.
Philip M HansbroCenter for Inflammation, Centenary Institute and University of Technology Sydney, Faculty of Science, School of Life Sciences, Sydney, NSW 2006, Australia.
Hans-Martin JäckDivision of Molecular Immunology, University Hospital Erlangen, University of Erlangen-Nürnberg, Erlangen 91054, Germany.
Stuart TurvilleUNSW Sydney, Faculty of Medicine, Sydney, NSW 2010, Australia; Kirby Institute, UNSW, Sydney, NSW 2052, Australia.
Daniel ChristGarvan Institute of Medical Research, Sydney, NSW 2010, Australia; UNSW Sydney, Faculty of Medicine, Sydney, NSW 2010, Australia.
Christopher C GoodnowGarvan Institute of Medical Research, Sydney, NSW 2010, Australia; Cellular Genomics Futures Institute, UNSW Sydney, Sydney, NSW 2052, Australia.
Garvan Institute of Medical Research · AUUNSW Sydney · AUUniversitätsklinikum Erlangen · DEUniversity of Technology Sydney · AUFriedrich-Alexander-Universität Erlangen-Nürnberg · DEAustralian National University · AUNew South Wales Department of Health · AUThe University of Sydney · AUVictor Chang Cardiac Research Institute · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

AnimalsAntibodies, NeutralizingAntibodies, ViralBetacoronavirusConserved SequenceCoronavirus InfectionsCOVID-19 VaccinesEvolution, MolecularHumansImmunizationMiceMice, Inbred BALB CMice, Inbred C57BLProtein BindingProtein DomainsSevere acute respiratory syndrome-related coronavirusAntibodies, NeutralizingAntibodies, ViralCOVID-19 VaccinesSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2antigenic variationclass 4 epitope sitecross-reactivityepitope conservationescape mutationshuman antibodiesmouse modelneutralizationnext generation vaccinesSARS-CoV-2variants of concern

Identifiers

PMID34788600
PMCPMC8554075
OpenAlexW3209400791

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.