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TitleDeep repertoire mining uncovers ultra-broad coronavirus neutralizing antibodies targeting multiple spike epitopes.
Journal, issue, pagesCell Rep, Vol. 43, Issue 6, Page 114307, Year 2024
Publish dateJun 5, 2024
AuthorsJonathan Hurtado / Thomas F Rogers / David B Jaffe / Bruce A Adams / Sandhya Bangaru / Elijah Garcia / Tazio Capozzola / Terrence Messmer / Pragati Sharma / Ge Song / Nathan Beutler / Wanting He / Katharina Dueker / Rami Musharrafieh / Sarah Burbach / Alina Truong / Michael J T Stubbington / Dennis R Burton / Raiees Andrabi / Andrew B Ward / Wyatt J McDonnell / Bryan Briney /
PubMed AbstractThe development of vaccines and therapeutics that are broadly effective against known and emergent coronaviruses is an urgent priority. We screened the circulating B cell repertoires of COVID-19 ...The development of vaccines and therapeutics that are broadly effective against known and emergent coronaviruses is an urgent priority. We screened the circulating B cell repertoires of COVID-19 survivors and vaccinees to isolate over 9,000 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific monoclonal antibodies (mAbs), providing an expansive view of the SARS-CoV-2-specific Ab repertoire. Among the recovered antibodies was TXG-0078, an N-terminal domain (NTD)-specific neutralizing mAb that recognizes diverse alpha- and beta-coronaviruses. TXG-0078 achieves its exceptional binding breadth while utilizing the same VH1-24 variable gene signature and heavy-chain-dominant binding pattern seen in other NTD-supersite-specific neutralizing Abs with much narrower specificity. We also report CC24.2, a pan-sarbecovirus neutralizing antibody that targets a unique receptor-binding domain (RBD) epitope and shows similar neutralization potency against all tested SARS-CoV-2 variants, including BQ.1.1 and XBB.1.5. A cocktail of TXG-0078 and CC24.2 shows protection in vivo, suggesting their potential use in variant-resistant therapeutic Ab cocktails and as templates for pan-coronavirus vaccine design.
External linksCell Rep / PubMed:38848216
MethodsEM (single particle)
Resolution3.17 - 3.88 Å
Structure data

EMDB-40812: Structure of SARS-CoV-2 (HP-GSAS-Mut7) spike in complex with TXG-0078 Fab -Conformation 1
Method: EM (single particle) / Resolution: 3.17 Å

EMDB-40813: Structure of SARS-CoV-2 (HP-GSAS-Mut7) spike in complex with TXG-0078 Fab -Conformation 2
Method: EM (single particle) / Resolution: 3.3 Å

40814

8swh

EMDB-40814, PDB-8swh:
Local refinement of SARS-CoV-2 (HP-GSAS-Mut7) spike NTD in complex with TXG-0078 Fab
Method: EM (single particle) / Resolution: 3.88 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • severe acute respiratory syndrome coronavirus 2
  • homo sapiens (human)
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / SARS-CoV-2 / spike / COVID / monoclonal antibody / complex / NTD / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex

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