A monoclonal antibody targeting a large surface of the receptor binding motif shows pan-neutralizing SARS-CoV-2 activity

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Feb. 5, 2024

Abstract Here we report the characterization of 17T2, a SARS-CoV-2 pan-neutralizing human monoclonal antibody isolated from COVID-19 convalescent individual infected during first pandemic wave. 17T2 is class 1 VH1-58/κ3-20 antibody, derived receptor binding domain (RBD)-specific IgA + memory B cell, with broad neutralizing activity against former and new variants, including XBB.1.16 BA.2.86 Omicron subvariants. Consistently, demonstrates in vivo prophylactic therapeutic BA.1.1 infection K18-hACE2 mice. Cryo-electron microscopy reconstruction shows that binds BA.1 spike RBD “up” position blocks motif, as other structurally similar antibodies do, S2E12. Yet, unlike S2E12, retains its all variants tested, probably due to larger contact area. These results highlight impact small structural changes on performance identify potential candidate for future clinical interventions.

Language: Английский

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A Mn²⁺‐Assisted Nanofiber‐Hydrogel Adjuvant for Simultaneous Enhancement of Humoral and Cellular Immune Responses

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: 34(30)

Published: April 9, 2024

Abstract Limited ability to elicit cellular immune responses has restricted the effectiveness of conventional adjuvants in context cancers. Recent advancements innate activation mechanism investigations have paved way for implementation a “bottom‐up” approach development novel adjuvants. Herein, simple hydrogel adjuvant with uniformly organized nanoscale microstructure, termed MnP gel is devised, by employing self‐assembling peptides incorporated manganese ions (Mn 2+ ). exhibits Mn sustained‐release properties vivo and effectively promotes germinal center formation, thereby facilitating generation antibodies at levels comparable aluminum‐based Moreover, transcends scope humoral immunity, demonstrating robustly trigger positioning it as promising candidate cancer prevention treatments. In conclusion, work introduced well‐defined proof‐of‐concept, simplifying vaccine design opening up new avenues “on‐demand” immunomodulation strategies.

Language: Английский

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Neutralizing antibodies to block viral entry and for identification of entry inhibitors

Antiviral Research, Journal Year: 2024, Volume and Issue: 224, P. 105834 - 105834

Published: Feb. 17, 2024

Language: Английский

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A generalized framework to identify SARS-CoV-2 broadly neutralizing antibodies

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 18, 2024

Abstract Monoclonal antibodies (mAbs) targeting the SARS-CoV-2 receptor-binding domain (RBD) showed high efficacy in prevention and treatment of COVID-19. However, rapid evolution has rendered all clinically authorized mAbs ineffective continues to stymie development next-generation mAbs. Consequently, ability identify broadly neutralizing (bnAbs) that neutralize both current future variants is critical for successful antibody therapeutic development, especially newly emerged viruses when no knowledge about immune evasive available. Here, we have developed a strategy specifically select potent bnAbs with activity against existing prospective based on accurate viral prediction informed by deep mutational scanning (DMS). By adopting this methodology, increased probability identifying XBB.1.5-effective from ∼1% 40% if were at early stage pandemic, as revealed retrospective analysis >1,000 wildtype (WT)-elicited From collection, identified bnAb, designated BD55-1205, exhibited exceptional historical, contemporary, predicted variants. Structural analyses extensive polar interactions between BD55-1205 XBB.1.5 motif (RBM), backbone atoms, explaining its unusually broad reactivity. Importantly, mRNA-based delivery IgG human FcRn-expressing transgenic mice resulted serum titers selected XBB BA.2.86 subvariants. Together, via prediction, coupled speed flexibility mRNA technology, provides generalized framework antibody-based countermeasures potentially other highly variable pathogens pandemic potential.

Language: Английский

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Emerging and reemerging infectious diseases: global trends and new strategies for their prevention and control

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Sept. 11, 2024

Language: Английский

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