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-Structure paper
| タイトル | First-generation N-terminal domain supersite public antibodies retain activity against Omicron-derived lineages and protect mice against Omicron BA.5 challenge. |
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| ジャーナル・号・ページ | mBio, Vol. 16, Issue 10, Page e0103625, Year 2025 |
| 掲載日 | 2025年10月8日 |
著者 | Vincent Dussupt / Jaime L Jensen / Paul V Thomas / Letzibeth Mendez-Rivera / Kerri G Lal / Michelle Zemil McCrea / Isabella Swafford / Joana Hernandez / Rajeshwer S Sankhala / Mekhala Rao / Juhi Arora / Agnes Hajduczki / Ningbo Jian / Phyllis A Rees / Indica Showell-De Leon / Gabriel Smith / Lauren Smith / Diana Wasson / Annika Schmid / I-Ting Teng / Tongqing Zhou / Peter D Kwong / Jeffrey R Currier / William W Reiley / Dominic Paquin-Proulx / Victoria R Polonis / Natalie D Collins / Nelson L Michael / M Gordon Joyce / Shelly J Krebs / ![]() |
| PubMed 要旨 | Monoclonal antibodies to SARS-CoV-2 can offer prophylactic and therapeutic protection against severe disease, with particular utility for immunosuppressed and vulnerable populations. With the ...Monoclonal antibodies to SARS-CoV-2 can offer prophylactic and therapeutic protection against severe disease, with particular utility for immunosuppressed and vulnerable populations. With the constant emergence of new variants, understanding the neutralizing potency of monoclonal antibodies to dynamic spike protein epitopes is crucial. We show that a set of VH1-24-derived N-terminal domain (NTD)-directed antibodies, isolated from a convalescent donor early in the pandemic, displayed remarkable neutralization resilience against many Omicron SARS-CoV-2 variants, including BA.2, BA.5, and BQ.1.1. Neutralization potency to these Omicron variants is associated with slower off-rates to the spike protein. Structural characterization of the most potent NTD antibody, WRAIR-2008, revealed a conserved mode of interaction shared with other antibodies of the same multi-donor class. WRAIR-2008 protected mice from weight loss following BA.5 challenge and reduced infectious viral titers in the lungs. Our study highlights the retention of neutralization activity and protection of first-generation VH1-24-derived NTD-directed antibodies to specific Omicron variants and provides valuable insights into the shifting landscape of SARS-CoV-2 variants that are vulnerable to select monoclonal antibodies. IMPORTANCE: As SARS-CoV-2 circulating variants evolve, it is important to understand the vulnerabilities of these viruses to neutralizing antibodies. Within this manuscript, we describe first-generation antibodies isolated following infection with WA-1 that retain viral neutralization to subsequent Omicron variants by targeting a site of viral vulnerability called the NTD. This work highlights the shifting landscape of SARS-CoV-2 variants and provides mechanistic insights into how antibodies from prior infections may play a role in preventing subsequent SARS-CoV-2 variant infections. |
リンク | mBio / PubMed:40882161 / PubMed Central |
| 手法 | EM (単粒子) / X線回折 |
| 解像度 | 1.54 - 3.89 Å |
| 構造データ | EMDB-47928, PDB-9ecz: EMDB-48284, PDB-9mi3: ![]() PDB-9ecx: ![]() PDB-9ecy: |
| 化合物 | ![]() ChemComp-GOL: ![]() ChemComp-SO4: ![]() ChemComp-HOH: ![]() ChemComp-PE5: ![]() ChemComp-NAG: |
| 由来 |
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キーワード | IMMUNE SYSTEM / antibody / neutralizing antibody / human antibody / SARS-CoV-2 / VIRAL PROTEIN/IMMUNE SYSTEM / viral protein / HexaPro / VIRAL PROTEIN-IMMUNE SYSTEM complex / severe acute respiratory syndrome coronavirus 2 |
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