Identification of an IGHV3-53-Encoded RBD-Targeting Cross-Neutralizing Antibody from an Early COVID-19 Convalescent DOI Creative Commons
Yuanyuan Hu, Caiqin Hu, Shuo Wang

и другие.

Pathogens, Год журнала: 2024, Номер 13(4), С. 272 - 272

Опубликована: Март 23, 2024

Since November 2021, Omicron has emerged as the dominant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, and its sublineages continue to appear one after another, significantly reducing effectiveness of existing therapeutic neutralizing antibodies (NAbs). It is urgent develop effective NAbs against circulating variants. Here, we isolated receptor binding domain (RBD)-specific single memory B cells via flow cytometry from a COVID-19 convalescent. The antibody variable region genes heavy chain (VHs) light (VLs) were amplified cloned into expression vectors. After expression, ELISA screening activity detection, obtained an IGHV3-53-encoded RBD-targeting cross-neutralizing D6, whose VL originated IGKV1-9*01 germlines. D6 could potently neutralize variants (BA.1, BA.2, BA.4/5 BF.7), with IC50 values less than 0.04 μg/mL, ability XBB was reduced but still effective. KD RBD prototype BA.1 both 1.0 × 10−12 M. protein structure D6-RBD model indicates that interacts external subdomain belongs RBD-1 community. sufficient contact deep interaction HCDR3 LCDR3 may be crucial reason for activity. sorting analysis mAb will provide important information development anti-COVID-19 reagents.

Язык: Английский

A lung-selective delivery of mRNA encoding broadly neutralizing antibody against SARS-CoV-2 infection DOI Creative Commons
Wanbo Tai, Kai Yang, Yubin Liu

и другие.

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Дек. 5, 2023

Abstract The respiratory system, especially the lung, is key site of pathological injury induced by SARS-CoV-2 infection. Given low feasibility targeted delivery antibodies into lungs intravenous administration and short half-life period in intranasal or aerosolized immunization, mRNA encoding broadly neutralizing with lung-targeting capability can perfectly provide high-titer to prevent Here, we firstly identify a human monoclonal antibody, 8-9D, broad potency against variants. neutralization mechanism this antibody explained structural characteristics 8-9D Fabs complex Omicron BA.5 spike. In addition, evaluate efficacy using safe robust platform compare performance when its not selectively delivered lungs. lung-selective enables expression which blocks invasion virus, thus effectively protecting female K18-hACE2 transgenic mice from challenge Beta BA.1 variant. Our work underscores potential application prevention treatment infections caused circulating

Язык: Английский

Процитировано

23
Potent and broadly neutralizing antibodies against sarbecoviruses induced by sequential COVID-19 vaccination DOI Creative Commons
Xiaoyu Zhao, Tianyi Qiu, Xiner Huang

и другие.

Cell Discovery, Год журнала: 2024, Номер 10(1)

Опубликована: Фев. 6, 2024

Abstract The current SARS-CoV-2 variants strikingly evade all authorized monoclonal antibodies and threaten the efficacy of serum-neutralizing activity elicited by vaccination or prior infection, urging need to develop antivirals against related sarbecoviruses. Here, we identified both potent broadly neutralizing from a five-dose vaccinated donor who exhibited cross-reactive diverse coronaviruses. Through single B-cell sorting sequencing followed tailor-made computational pipeline, successfully selected 86 with potential cross-neutralizing ability 684 antibody sequences. Among them, PW5-570 potently neutralized that arose Omicron BA.5, other three could neutralize concern, SARS-CoV their sarbecoviruses (Pangolin-GD, RaTG13, WIV-1, SHC014). Cryo-EM analysis demonstrates these have neutralization mechanisms, such as disassembling spike trimers, binding RBM SD1 affect ACE2 binding. In addition, prophylactic administration significantly protects nasal turbinate lung infections BA.1, XBB.1, viral challenge in golden Syrian hamsters, respectively. Importantly, post-exposure treatment PW5-5 PW5-535 also markedly XBB.1 models. This study reveals utility process assist screening antibodies, well potency vaccine-induced sarbecoviruses, offering promising avenues for development broad therapeutic drugs.

Язык: Английский

Процитировано

15
Vaccine adjuvants: current status, research and development, licensing, and future opportunities DOI
Ying Cui,

Megan Ho,

Yongjie Hu

и другие.

Journal of Materials Chemistry B, Год журнала: 2024, Номер 12(17), С. 4118 - 4137

Опубликована: Янв. 1, 2024

A comprehensive review of the current landscape and advancements in vaccine adjuvants, providing critical insights into research, development, regulatory licensing, potential future opportunities for enhancing efficacy safety.

Язык: Английский

Процитировано

11
SARS-CoV-2 JN.1 variant evasion of IGHV3-53/3-66 B cell germlines DOI Open Access
Ida Paciello, Giuseppe Maccari, Giulio Pierleoni

и другие.

Science Immunology, Год журнала: 2024, Номер 9(98)

Опубликована: Авг. 9, 2024

The severe acute respiratory syndrome coronavirus 2 variant JN.1 recently emerged as the dominant despite having only one amino acid change on spike (S) protein receptor binding domain (RBD) compared with ancestral BA.2.86, which never represented more than 5% of global variants. To define at molecular level ability to spread globally, we interrogated a panel 899 neutralizing human monoclonal antibodies. Our data show that single leucine-455-to-serine mutation in RBD unleashed JN.1, likely occurring by elimination 70% antibodies mediated IGHV3-53/3-66 germlines. However, resilience class 3 low neutralization potency but strong Fc functions may explain absence disease.

Язык: Английский

Процитировано

8
Broadly neutralizing antibodies against COVID-19 DOI Creative Commons
Daming Zhou, Jingshan Ren, Elizabeth E. Fry

и другие.

Current Opinion in Virology, Год журнала: 2023, Номер 61, С. 101332 - 101332

Опубликована: Июнь 7, 2023

The COVID-19 pandemic caused by SARS-CoV-2 has led to hundreds of millions infections and deaths, however, human monoclonal antibodies (mAbs) can be an effective treatment. Since emerged, a variety strains have acquired increasing numbers mutations gain increased transmissibility escape from the immune response. Most reported neutralizing mAbs, including all approved therapeutic ones, been knocked down or out these mutations. Broadly mAbs are therefore great value, treat current possible future variants. Here, we review four types against spike protein with broad potency previously currently circulating These target receptor-binding domain, subdomain 1, stem helix, fusion peptide. Understanding how retain in face mutational change could guide development vaccines.

Язык: Английский

Процитировано

19
Comprehensive Overview of Broadly Neutralizing Antibodies against SARS-COV-2 Variants DOI Open Access

Lingyan Cui,

Tingting Li,

Wenhui Xue

и другие.

Опубликована: Апрель 10, 2024

Currently, SARS-CoV-2 has evolved into various variants, including the numerous highly mutated Omicron sub-lineages, significantly increasing immune evasion ability. The development raises concerns about possibly diminished effectiveness of available vaccines and antibody-based therapeutics. Here, we describe those representative categories broadly neutralizing antibodies (bnAbs) that retain prominent against emerging variants sub-lineages. molecular characteristics, epitope conservation, resistance mechanisms these are further detailed, aiming to offer suggestion or direction for therapeutic antibodies, facilitate vaccine design with broad-spectrum potential.

Язык: Английский

Процитировано

6
Comprehensive Overview of Broadly Neutralizing Antibodies against SARS-CoV-2 Variants DOI Creative Commons

Lingyan Cui,

Tingting Li,

Wenhui Xue

и другие.

Viruses, Год журнала: 2024, Номер 16(6), С. 900 - 900

Опубликована: Июнь 1, 2024

Currently, SARS-CoV-2 has evolved into various variants, including the numerous highly mutated Omicron sub-lineages, significantly increasing immune evasion ability. The development raises concerns about possibly diminished effectiveness of available vaccines and antibody-based therapeutics. Here, we describe those representative categories broadly neutralizing antibodies (bnAbs) that retain prominent against emerging variants sub-lineages. molecular characteristics, epitope conservation, resistance mechanisms these are further detailed, aiming to offer suggestion or direction for therapeutic antibodies, facilitate design with broad-spectrum potential.

Язык: Английский

Процитировано

5
Antigenic sin and multiple breakthrough infections drive converging evolution of COVID-19 neutralizing responses DOI Creative Commons
Ida Paciello, Giulio Pierleoni, Elisa Pantano

и другие.

Cell Reports, Год журнала: 2024, Номер 43(9), С. 114645 - 114645

Опубликована: Авг. 27, 2024

Understanding the evolution of B cell response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants is fundamental design next generation vaccines and therapeutics. We longitudinally analyze at single-cell level almost 900 neutralizing human monoclonal antibodies (nAbs) isolated from vaccinated people individuals with hybrid super immunity (SH), developed after three mRNA vaccine doses two breakthrough infections. The most potent neutralization Fc functions against highly mutated belong SH cohort. Repertoire analysis shows that original Wuhan antigenic sin drives convergent expansion same germlines in cohorts. Only Omicron infections expand previously unseen germ lines generate broadly nAbs by restoring IGHV3-53/3-66 lines. Our analyses find cells initially expanded continue play a role immune toward an evolving virus.

Язык: Английский

Процитировано

4
Efficacy of Inactivated Bivalent SARS-CoV-2 Vaccines Targeting Ancestral Strain (ERAGEM), Delta, and Omicron Variants DOI Creative Commons
B. S. Kaplan, Shaikh Terkıs Islam Pavel, Muhammet Ali Uygut

и другие.

Vaccines, Год журнала: 2025, Номер 13(2), С. 169 - 169

Опубликована: Фев. 10, 2025

Background/Objectives: The rapid evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the emergence variants with enhanced transmissibility and immune evasion, challenging existing vaccines. This study aimed evaluate immunogenicity protective efficacy inactivated bivalent vaccine formulations incorporating ancestral SARS-CoV-2 strain (ERAGEM) either Delta or Omicron (BA.5) variants. Methods: Bivalent were prepared using beta-propiolactone-inactivated antigens administered K18-hACE2 transgenic mice. Following prime booster immunizations, neutralizing antibody titers viral loads assessed through ELISA, microneutralization assays, quantitative PCR. Mice challenged respective variants, survival rates, temperature, body weight changes monitored for 21 days. Results: Both elicited significant increases in post-booster immunization. ERAGEM + group demonstrated geometric mean (GMTs) 6938.1 4935.0 respectively, while achieved GMTs 16,280.7 24,215.9 Complete (100%) was observed all vaccinated groups post-challenge, no detectable lungs substantial reductions nasal turbinate compared unvaccinated controls. Conclusions: vaccines strong complete protection against disease preclinical models. These findings indicate potential strategies addressing antigenic diversity preparing future pandemics caused by rapidly evolving pathogens.

Язык: Английский

Процитировано

0
Learning the language of protein–protein interactions DOI Creative Commons

Varun Ullanat,

Bowen Jing,

Samuel Sledzieski

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Март 10, 2025

Protein Language Models (PLMs) trained on large databases of protein sequences have proven effective in modeling biology across a wide range applications. However, while PLMs excel at capturing individual properties, they face challenges natively representing protein–protein interactions (PPIs), which are crucial to understanding cellular processes and disease mechanisms. Here, we introduce MINT, PLM specifically designed model sets interacting proteins contextual scalable manner. Using unsupervised training curated PPI dataset derived from the STRING database, MINT outperforms existing diverse tasks relating interactions, including binding affinity prediction estimation mutational effects. Beyond these core capabilities, it excels complex assemblies surpasses specialized models antibody–antigen T cell receptor–epitope prediction. MINT's predictions impacts oncogenic PPIs align with experimental studies, provides reliable estimates for potential cross–neutralization antibodies against SARS–CoV–2 variants concern. These findings position as powerful tool elucidating significant implications biomedical research therapeutic discovery.

Язык: Английский

Процитировано

0