9CCJ

Dissecting human monoclonal antibody responses from mRNA and protein-based booster vaccinations against XBB1.5 SARS-CoV-2

9CCJ の概要

• エントリーDOI: 10.2210/pdb9ccj/pdb
• EMDBエントリー: 45444
• 分子名称: M2 Fab Heavy Chain, M2 Fab Light Chain, Spike glycoprotein, ... (6 entities in total)
• 機能のキーワード: sars-cov-2, antibody, ntd, immune system, virus like particle, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 184362.38

構造登録者

Bajic, G.,Civljak, A. (登録日: 2024-06-21, 公開日: 2025-03-12)

主引用文献

Fantin, R.F.,Clark, J.J.,Cohn, H.,Jaiswal, D.,Bozarth, B.,Civljak, A.,Rao, V.,Lobo, I.,Nardulli, J.R.,Srivastava, K.,Yong, J.,Andreata-Santos, R.,Bushfield, K.,Lee, E.S.,Singh, G.,Kleinstein, S.H.,Krammer, F.,Simon, V.,Bajic, G.,Coelho, C.H.
Dissecting human monoclonal antibody responses from mRNA- and protein-based XBB.1.5 COVID-19 monovalent vaccines.
Biorxiv, 2024

PubMed Abstract: The emergence of highly contagious and immune-evasive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has required reformulation of coronavirus disease 2019 (COVID-19) vaccines to target those new variants specifically. While previous infections and booster vaccinations can enhance variant neutralization, it is unclear whether the monovalent version, administered using either mRNA or protein-based vaccine platforms, can elicit B-cell responses specific for Omicron XBB.1.5 variants. Here, we dissected the genetic antibody repertoire of 603 individual plasmablasts derived from five individuals who received a monovalent XBB.1.5 vaccination either with mRNA (Moderna or Pfizer/BioNtech) or adjuvanted protein (Novavax). From these sequences, we expressed 100 human monoclonal antibodies and determined binding, affinity and protective potential against several SARS-CoV-2 variants, including JN.1. We then select two vaccine-induced XBB.1.5 mAbs, M2 and M39. M2 mAb was a , antibody, i.e., specific for XBB.1.5 but not ancestral SARS-CoV-2. M39 bound and neutralized both XBB.1.5 and JN.1 strains. Our high-resolution cryo-electron microscopy (EM) structures of M2 and M39 in complex with the XBB.1.5 spike glycoprotein defined the epitopes engaged and revealed the molecular determinants for the mAbs' specificity. These data show, at the molecular level, that monovalent, variant-specific vaccines can elicit functional antibodies, and shed light on potential functional and genetic differences of mAbs induced by vaccinations with different vaccine platforms.\.

PubMed: 39071292
DOI: 10.1101/2024.07.15.602781

実験手法

ELECTRON MICROSCOPY (2.37 Å)