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TitleHeterologous betacoronavirus spike immunization in non-human primates elicits antibodies that neutralize both sarbeco- and merbecoviruses.
Journal, issue, pagesCell Rep, Vol. 45, Issue 6, Page 117439, Year 2026
Publish dateJun 23, 2026
AuthorsKatharina Dueker / Tazio Capozzola / Ziqi Feng / Ryan N Lin / Jonathan Hurtado / Sandhya Bangaru / Meng Yuan / Nathan Beutler / Elijah Garcia / Wan-Ting He / Sean Callaghan / Gabriel Avillion / Lina Vo / Xuduo Li / Jonathan L Torres / Rami Musharrafieh / Ge Song / Nitesh Mishra / Pragati Sharma / Peter Yong / Fabio Anzanello / Katarzyna Kaczmarek Michaels / Elana Ben-Akiva / Murillo Silva / Mariane Melo / Muzamil Makhdoomi / Ethan Westfall-Gomez / William Rinaldi / Melissa Ferguson / Yana Safonova / Shane Crotty / Darrell J Irvine / Thomas Rogers / Andrew B Ward / Bryan Briney / Ian A Wilson / Dennis R Burton / Raiees Andrabi /
PubMed AbstractIn anticipation of future coronavirus (CoV) pandemics, developing vaccines that elicit broadly neutralizing antibodies (bnAbs) against diverse CoVs is critical. Here, we vaccinated rhesus macaques ...In anticipation of future coronavirus (CoV) pandemics, developing vaccines that elicit broadly neutralizing antibodies (bnAbs) against diverse CoVs is critical. Here, we vaccinated rhesus macaques with the SARS-CoV-2 spike (S)-protein, then boosted with heterologous β-CoV S-proteins to focus responses to common conserved S2 bnAb epitopes. Initial SARS-CoV-2 priming elicited receptor-binding domain (RBD)-focused responses, while MERS-CoV boosting redirected responses toward the S2 region, including the stem-helix bnAb site. Although S2-directed serum cross-neutralization was undetectable and most isolated cross-reactive monoclonal antibodies (mAbs) targeted non-neutralizing epitopes, two S2 stem-helix mAbs were identified from memory B cells. These bnAbs neutralized diverse sarbeco- and merbecoviruses, including MERS-CoV, and conferred robust in vivo protection against SARS-CoV-2 challenge. Structural studies reveal that these macaque bnAbs closely mimic human S2 stem bnAbs induced by infection. These findings provide proof-of-principle for vaccination strategies that elicit broadly protective β-coronavirus responses and highlight non-human primates as a translational model for evaluating S2-targeted immunogens.
External linksCell Rep / PubMed:42241278
MethodsEM (single particle) / X-ray diffraction
Resolution3.07 - 25.0 Å
Structure data

EMDB-70024: Rhesus Macaque mAb CHM-27 complexed with SARS-CoV-2 spike protein
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-70025: Rhesus Macaque mAb CHM-16 complexed with SARS-CoV-2 spike protein
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-70026: Rhesus Macaque DHIK wk40 polyFab + SARS-CoV-2 Spike
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-70027: Rhesus Macaque DHJB wk12 polyFab + SARS-CoV-2 Spike
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-70028: Rhesus Macaque L603 wk53 polyFab + SARS-CoV-2 Spike
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-70029: Rhesus Macaque L603 wk40 polyFab + SARS-CoV-2 Spike
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-70030: Rhesus Macaque DHJB wk40 polyFab + SARS-CoV-2 Spike
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-70031: Rhesus Macaque L603 wk12 polyFab + SARS-CoV-2 Spike
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-70032: Rhesus Macaque K620 wk12 polyFab + SARS-CoV-2 Spike
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-70033: Rhesus Macaque K620 wk53 polyFab + SARS-CoV-2 Spike
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-70034: Rhesus Macaque K620 wk40 polyFab + SARS-CoV-2 Spike
Method: EM (single particle) / Resolution: 25.0 Å

PDB-8tmy:
Crystal structure of SARS-CoV-2 spike stem helix peptide in complex with neutralizing antibody CHM-16
Method: X-RAY DIFFRACTION / Resolution: 3.07 Å

Chemicals

ChemComp-FLC:
CITRATE ANION

Source
  • Macaca (macaques)
  • macaca mulatta (Rhesus monkey)
  • severe acute respiratory syndrome coronavirus 2
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / Antibody / SARS-CoV-2 / Coronavirus / IMMUNE SYSTEM / VIRAL PROTEIN-IMMUNE SYSTEM complex

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