8TMY

Crystal structure of SARS-CoV-2 spike stem helix peptide in complex with neutralizing antibody CHM-16

Summary for 8TMY

• Entry DOI: 10.2210/pdb8tmy/pdb
• Descriptor: Stem helix peptide of Spike protein S2', Neutralizing antibody CHM-16 Heavy Chain, Neutralizing antibody CHM-16 Light Chain, ... (4 entities in total)
• Functional Keywords: antibody, sars-cov-2, coronavirus, immune system, viral protein-immune system complex, viral protein/immune system
• Biological source: Macaca mulatta (Rhesus monkey); More
• Total number of polymer chains: 9
• Total formula weight: 149806.68

Authors

Feng, Z.,Wilson, I.A. (deposition date: 2023-07-31, release date: 2024-07-31, Last modification date: 2026-08-26)

Primary citation

Dueker, K.,Capozzola, T.,Feng, Z.,Lin, R.N.,Hurtado, J.,Bangaru, S.,Yuan, M.,Beutler, N.,Garcia, E.,He, W.T.,Callaghan, S.,Avillion, G.,Vo, L.,Li, X.,Torres, J.L.,Musharrafieh, R.,Song, G.,Mishra, N.,Sharma, P.,Yong, P.,Anzanello, F.,Kaczmarek Michaels, K.,Ben-Akiva, E.,Silva, M.,Melo, M.,Makhdoomi, M.,Westfall-Gomez, E.,Rinaldi, W.,Ferguson, M.,Safonova, Y.,Crotty, S.,Irvine, D.J.,Rogers, T.,Ward, A.B.,Briney, B.,Wilson, I.A.,Burton, D.R.,Andrabi, R.
Heterologous betacoronavirus spike immunization in non-human primates elicits antibodies that neutralize both sarbeco- and merbecoviruses.
Cell Rep, 45:117439-117439, 2026

PubMed Abstract: 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.

PubMed: 42241278
DOI: 10.1016/j.celrep.2026.117439

Experimental method

X-RAY DIFFRACTION (3.07 Å)