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 Versatile High‐Throughput Single‐Cell Screening Platform for Profiling Antigen‐Specific Long‐Lived B Cells in Blood and Bone Marrow DOI Creative Commons
Tian Zhao, Yuqing Lei, Chang Liu

и другие.

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Апрель 9, 2025

Abstract Antigen‐specific B cells play a crucial role in the long‐term immune response following infection or vaccination, differentiating into antibody‐secreting (ASCs) and memory (MBCs). However, profiling ASCs is challenging primarily due to their lack of membrane‐bound surface cell receptors. In this study, Modular Superhydrophobic Microwell Array Chip (MoSMAR‐chip) introduced as versatile, cost‐effective, high‐throughput platform for identifying characterizing individual antigen‐specific MBCs at single‐cell level within seven days. Using platform, comprehensive analyses single could be performed from bone marrows coronavirus disease 2019 (COVID‐19) vaccine‐immunized mice diverse set antibodies capable neutralizing highly divergent JN1 variant severe acute respiratory syndrome 2 (SARS‐CoV‐2) were identified. These results demonstrate that MoSMAR‐chip facilitates efficient multi‐omics functional ASCs, offering powerful tool investigating complex immunity clinical conditions, such infectious diseases, autoimmunity, beyond.

Язык: Английский

Процитировано

0
1 μL, 40min: Multimodal COVID-19 antibody protection evaluation with tip optofluidic immunoassay DOI Creative Commons
Xiaotian Tan, Yujuan Chai, Ruihan Li

и другие.

hLife, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

0
Novel Trispecific Neutralizing Antibodies With Enhanced Potency and Breadth Against Pan‐Sarbecoviruses DOI Creative Commons
Rui Qiao, Yuanchen Liu, Qiyu Mao

и другие.

MedComm, Год журнала: 2025, Номер 6(5)

Опубликована: Апрель 21, 2025

ABSTRACT The ongoing emergence of new variants the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) underscores urgent need for developing antivirals targeting both SARS‐CoV‐2 and related sarbecoviruses. To this end, we designed novel trispecific antibodies, Tri‐1 Tri‐2, engineered by fusing single‐chain variable fragments (scFvs) a potent antibody (PW5‐570) to Fc region “Knob‐into‐Hole” bispecific antibodies (bsAbs) composed two distinct broad (PW5‐5 PW5‐535). Compared with parental Tri‐2 displayed enhanced binding affinities receptor‐binding domains SARS‐CoV, wild type, Omicron XBB.1.16, each arm contributed overall enhancement. Furthermore, pseudovirus neutralization assays revealed that effectively neutralized all tested variants, sarbecoviruses (Pangolin‐GD, RaTG13, WIV1, SHC014), demonstrating potency breadth superior any single antibody. Consistently, were found neutralize authentic SARS‐CoV IC 50 values comparable or better than those antibodies. Taken together, study highlights potential effectiveness as formats harnessing cross‐neutralizing in development multivalent agents combat current future SARS‐like coronaviruses.

Язык: Английский

Процитировано

0
Development of de-novo coronavirus 3-chymotrypsin-like protease (3CLpro) inhibitors since COVID-19 outbreak: A strategy to tackle challenges of persistent virus infection DOI
Lei Tian, Taotao Qiang,

Xiuding Yang

и другие.

European Journal of Medicinal Chemistry, Год журнала: 2023, Номер 264, С. 115979 - 115979

Опубликована: Ноя. 25, 2023

Язык: Английский

Процитировано

9
The development of a rapid, high-throughput neutralization assay using a SARS-CoV-2 reporter DOI
Rigel Suzuki,

Akifumi Kamiyama,

Hayato Ito

и другие.

Journal of Virological Methods, Год журнала: 2024, Номер 326, С. 114894 - 114894

Опубликована: Фев. 13, 2024

Язык: Английский

Процитировано

2
Single-domain antibodies against SARS-CoV-2 RBD from a two-stage phage screening of universal and focused synthetic libraries DOI Creative Commons
Fangfang Chen, Zhihong Liu, Wei Kang

и другие.

BMC Infectious Diseases, Год журнала: 2024, Номер 24(1)

Опубликована: Фев. 13, 2024

Abstract Background Coronavirus disease 2019 (COVID-19) is an evolving global pandemic, and nanobodies, as well other single-domain antibodies (sdAbs), have been recognized a potential diagnostic therapeutic tool for infectious diseases. High-throughput screening techniques such phage display developed alternative to in vivo immunization the discovery of antibody-like target-specific binders. Methods We designed constructed highly diverse synthetic library sdAb-U (single-domain Antibody - Universal ) based on human framework. The SARS-CoV-2 receptor-binding domain (RBD) was expressed purified. universal panned against RBD protein target two rounds, followed by monoclonal ELISA (enzyme-linked immunosorbent assay) identify RBD-specific binders (the first stage). High-affinity were sequenced obtained CDR1 CDR2 sequences combined with fully randomized CDR3 construct targeted (focused) sdAb-RBD, subsequent second-stage panning (also rounds) screening. Then, high single-to-background ratios selected expression. binding affinities sdAbs measured ELISA-based method. In addition, we conducted competition (using ACE2 ectodomain S19-D615) pseudovirus neutralization assays high-affinity RBD-binding sdAb39. Results Significant enrichments observed both first-stage (universal library) (focused panning. Five identified stage signal-to-background ratios. second stage, much higher possibility finding clones ELISA. Among 45 RBD-positive sequences, found eight can be expressed, five them show (EC 50 < 100nM). finally that sdAb39 ~ 4nM) compete RBD. Conclusion Overall, this two-stage strategy libraries enables rapid selection sdAb activity, potentially used targets.

Язык: Английский

Процитировано

2
Predicting antibody and ACE2 affinity for SARS-CoV-2 BA.2.86 and JN.1 with in silico protein modeling and docking DOI Creative Commons
Shirish Yasa, Sayal Guirales-Medrano, Denis Jacob Machado

и другие.

Frontiers in Virology, Год журнала: 2024, Номер 4

Опубликована: Июль 19, 2024

The emergence of SARS-CoV-2 lineages derived from Omicron, including BA.2.86 (nicknamed “Pirola”) and its relative, JN.1, has raised concerns about their potential impact on public personal health due to numerous novel mutations. Despite this, predicting implications based solely mutation counts proves challenging. Empirical evidence JN.1’s increased immune evasion capacity in relation previous variants is mixed. To improve predictions beyond what possible counts, we conducted extensive silico analyses the binding affinity between RBD different (Wuhan-Hu-1, BA.1/B.1.1.529, BA.2, XBB.1.5, BA.2.86, JN.1) neutralizing antibodies vaccinated or infected individuals, as well human angiotensin-converting enzyme 2 (ACE2) receptor. We observed no statistically significant difference JN.1 other variants. Therefore, conclude that new have pronounced escape infection compared However, minor reductions for both ACE2 were noted JN.1. Future research this area will benefit structural memory B-cell should emphasize importance choosing appropriate samples studies assess protection provided by vaccination infection. Moreover, fitness benefits genomic variation outside need be investigated. This contributes understanding variants’ health.

Язык: Английский

Процитировано

2
SARS‐CoV‐2 Evolution: Immune Dynamics, Omicron Specificity, and Predictive Modeling in Vaccinated Populations DOI Creative Commons
Xiaohan Zhang, Mansheng Li, Nana Zhang

и другие.

Advanced Science, Год журнала: 2024, Номер 11(40)

Опубликована: Авг. 29, 2024

Abstract Host immunity is central to the virus's spread dynamics, which significantly influenced by vaccination and prior infection experiences. In this work, we analyzed co‐evolution of SARS‐CoV‐2 mutation, angiotensin‐converting enzyme 2 (ACE2) receptor binding, neutralizing antibody (NAb) responses across various variants in 822 human mice vaccinated with different non‐Omicron Omicron vaccines analyzed. The link between vaccine efficacy type, dosing, post‐vaccination duration revealed. classification immune protection against co‐evolved genetic mutations vaccination. Additionally, a model, Prevalence Score (P‐Score) introduced, surpasses previous algorithm‐based models predicting potential prevalence new populations. hybrid combining wild‐type (WT) inactivated BA.4/5 mRNA may provide broad both variants, albeit EG.5.1 still posing risk. conclusion, these findings enhance understanding population variations valuable insights for future development public health strategies.

Язык: Английский

Процитировано

2
Ancestral SARS-CoV-2 immune imprinting persists on RBD but not NTD after sequential Omicron infections DOI Creative Commons
Zuowei Wang, Ling Li,

Ruiping Du

и другие.

iScience, Год журнала: 2024, Номер 28(1), С. 111557 - 111557

Опубликована: Дек. 9, 2024

Язык: Английский

Процитировано

2
Trivalent recombinant protein vaccine induces cross-neutralization against XBB lineage and JN.1 subvariants: preclinical and phase 1 clinical trials DOI Creative Commons
H. J. Yang, Weiqi Hong, Shi H

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Дек. 30, 2024

The immune escape capacities of XBB variants necessitate the authorization vaccines with these antigens. In this study, we produce three recombinant trimeric proteins from RBD sequences Delta, BA.5, and XBB.1.5, formulating a trivalent vaccine (Tri-Vac) an MF59-like adjuvant at 1:1:4 ratio. Tri-Vac demonstrates immunogenicity in female NIH mice, inducing cross-neutralization against various SARS-CoV-2 variants, including pre-Omicron Omicron BA.2.75, lineages. It elicits measurable antigen-specific T cell responses, germinal center B follicular helper effectively protecting live XBB.1.16 challenges. Protective immunity is maintained long-term, sustained neutralizing antibodies as well memory cells long-lived plasma observed by day 210 post-immunization. also serves candidate booster for enhancing after doses inactivated virus or mRNA vaccines. A phase 1 investigator-initiated trial was initiated to assess safety humans, focusing on primary endpoint adverse reactions within 7 days key secondary endpoints geometric mean titers (GMTs) serum 30 6 months post-vaccination, events serious post-vaccination. Preliminary data indicate has good immunogenicity, improving neutralization multiple JN.1, previously vaccinated individuals, highlighting its clinical potential variants. registration number ChiCTR2200067245.

Язык: Английский

Процитировано

2