Expert Review of Hematology, Journal Year: 2024, Volume and Issue: unknown
Published: Nov. 29, 2024
COVID-19 is a continuing challenge for immunocompromised patients with hematological malignancies. Such are at increased risk complications, including hospitalization, respiratory failure, delay of anti-cancer therapies, and even death. In addition to non-pharmacologic interventions, the main strategies prevention in such vaccination pre-exposure prophylaxis.
Language: Английский
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown
Published: Sept. 5, 2024
SUMMARY During the summer of 2024, COVID-19 cases surged globally, driven by variants derived from JN.1 subvariants SARS-CoV-2 that feature new mutations, particularly in N-terminal domain (NTD) spike protein. In this study, we report on neutralizing antibody (nAb) escape, infectivity, fusion, and stability these subvariants—LB.1, KP.2.3, KP.3, KP.3.1.1. Our findings demonstrate all are highly evasive nAbs elicited bivalent mRNA vaccine, XBB.1.5 monovalent mumps virus-based or infections during BA.2.86/JN.1 wave. This reduction nAb titers is primarily a single serine deletion (DelS31) NTD spike, leading to distinct antigenic profile compared parental other variants. We also found DelS31 mutation decreases pseudovirus infectivity CaLu-3 cells, which correlates with impaired cell-cell fusion. Additionally, protein appears more conformationally stable, as indicated reduced S1 shedding both without stimulation soluble ACE2, increased resistance elevated temperatures. Molecular modeling suggests induces conformational change stabilizes strengthens NTD-Receptor-Binding Domain (RBD) interaction, thus favoring down conformation RBD reducing accessibility ACE2 receptor certain nAbs. introduces an N-linked glycan modification at N30, shields underlying region recognition. data highlight critical role mutations for evasion, stability, viral suggest consideration updating vaccines antigens containing DelS31.
Language: Английский
Citations
13
mBio, Journal Year: 2025, Volume and Issue: unknown
Published: March 26, 2025
ABSTRACT During the summer of 2024, coronavirus disease 2019 (COVID-19) cases surged globally, driven by variants derived from JN.1 subvariants severe acute respiratory syndrome 2 that feature new mutations, particularly in N-terminal domain (NTD) spike protein. In this study, we report on neutralizing antibody (nAb) escape, infectivity, fusion, and stability these subvariants—LB.1, KP.2.3, KP.3, KP.3.1.1. Our findings demonstrate all are highly evasive nAbs elicited bivalent mRNA vaccine, XBB.1.5 monovalent mumps virus-based or infections during BA.2.86/JN.1 wave. This reduction nAb titers is primarily a single serine deletion (DelS31) NTD spike, leading to distinct antigenic profile compared parental other variants. We also found DelS31 mutation decreases pseudovirus infectivity CaLu-3 cells, which correlates with impaired cell-cell fusion. Additionally, protein appears more conformationally stable, as indicated reduced S1 shedding both without stimulation soluble ACE2 increased resistance elevated temperatures. Molecular modeling suggests enhances NTD-receptor-binding (RBD) interaction, favoring RBD down conformation reducing accessibility specific nAbs. Moreover, introduces an N-linked glycan at N30, shielding recognition. These underscore role mutations immune evasion, stability, viral highlighting need consider DelS31-containing antigens updated COVID-19 vaccines. IMPORTANCE The emergence novel continues pose challenges for global public health, context evasion stability. study identifies key mutation, DelS31, JN.1-derived escape while stabilizes conformation, limits shedding, increases thermal resistance, possibly contribute prolonged persistence. Structural analyses reveal interactions introducing shielding, thus decreasing accessibility. emphasize critical shaping evolution underscoring urgent vaccines account adaptive changes.
Language: Английский
Citations
1
Published: Nov. 10, 2024
Abstract Pemivibart (Pemgarda™/VYD222) was granted Emergency Use Authorization (EUA) by the U.S. Food and Drug Administration (FDA) on March 22, 2024, for COVID-19 pre-exposure prophylaxis in immunocompromised individuals. However, its efficacy resistance against JN.1 sublineages have yet to be fully characterized. Here, we first assessed neutralizing activity of a panel VSV-based pseudoviruses representing contemporary sublineages, including XEC, fastest-growing SARS-CoV-2 strain globally, both Vero-E6 Vero-E6-TMPRSS2-T2A-hACE2 (Vero-E6-TA) cells. We then engineered replication-competent vesicular stomatitis virus with spike (rVSVΔG-JN.1) select escape variants performed structural analyses comprehensively map Pemivibart’s mutations. Our results demonstrated that exhibited comparable neutralization patterns cell lines retains broad effectiveness tested. potency remarkably reduced KP.3.1.1 IC 50 values approximately 4.2 µg/mL, about 22-fold higher than JN.1, as well JN.1-derived Pemivibart-escape mutants harbouring low-frequency mutations across strains through mutiple antibody evasion mechanisms Vero-E6-TA Collectively, our findings underscored importance monitoring clinical continue evolve. The profile could provide valuable insights forecasting optimizing emerging variants.
Language: Английский
Citations
6
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown
Published: Aug. 21, 2024
ABSTRACT First-generation anti-SARS-CoV-2 monoclonal antibodies (mAbs) used for prophylaxis or therapeutic purposes in immunocompromised patients have been withdrawn because of the emergence resistant Omicron variants. In 2024, two novel mAbs, Pemivibart and Sipavibart, approved by health authorities, but their activity against contemporary JN.1 sublineages is poorly characterized. We isolated authentic JN.1.1, KP1.1, LB.1 KP3.3 viruses evaluated sensitivity to neutralization these mAbs target cell lines. Compared ancestral strains, remained moderately active sub-variants, with a strong increase 50% Inhibitory Concentration (IC50), reaching up 3 15 μg/ml KP3.3. Sipavibart neutralized JN.1.1 lost antiviral efficacy Our results highlight need close clinical monitoring raise concerns about Sipavibart.
Language: Английский
Citations
3
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown
Published: Nov. 13, 2024
Abstract Pemivibart is a monoclonal antibody therapy currently under Emergency Use Authorization for the pre-exposure prophylaxis of coronavirus disease 2019 (COVID-19) in adults and adolescents over 12 years age with certain immunocompromised conditions. As part overall monitoring strategy activity pemivibart, regularly evaluated against emerging variants SARS-CoV-2 using pseudovirus neutralization assays. Recent clinical data from Invivyd demonstrates that PhenoSense assays carried out at Monogram Biosciences have been reliable consistent predictor continued pemivibart SARS-COV-2 predominated across timespan includes CANOPY trial post-EUA authorization period. Additionally, new potential antibodies based upon structural framework are continuously evaluation. Fifteen these yeast-produced “pemivibart-like” were tested recent KP.3 KP.3.1.1. Like all 15 maintained KP.3.1.1, change IC 50 averaging 2.51-fold +/-0.7 compared to KP.3. Four pemivibart-like also XEC variant, 3.01-fold These suggest KP.3.1.1 XEC, containing N-terminal domain modifications.
Language: Английский
Citations
1
Viruses, Journal Year: 2024, Volume and Issue: 16(11), P. 1686 - 1686
Published: Oct. 29, 2024
The coronavirus disease 2019 (COVID-19) pandemic, driven by the emergence of severe acute respiratory syndrome 2 (SARS-CoV-2), has been characterized virus's ongoing evolution, leading to appearance more transmissible variants that have often triggered infection surges. In this study, we analyzed SARS-CoV-2 epidemic in Cyprus, utilizing 1627 viral sequences from infected individuals between November 2022 and February 2024. Over period, 251 distinct lineages sublineages were identified, predominantly categorized into three groups: Omicron 5, XBB, JN.1 (parental lineage BA.2.86), all which harbor S protein mutations linked enhanced transmissibility immune escape. Despite relatively low numbers new infections during lack any major waves, unlike earlier phases these demonstrated varying periods dominance, with 5 prevailing 2023, XBB March generating a wavelet December 2023 These findings suggest Cyprus reached endemicity, gradually replacing previously circulating irrespective seasonal patterns. This study highlights critical importance surveillance evolution emphasizes role preventive measures limiting virus transmission, providing valuable insights for safeguarding public health.
Language: Английский
Citations
0
Expert Review of Hematology, Journal Year: 2024, Volume and Issue: unknown
Published: Nov. 29, 2024
COVID-19 is a continuing challenge for immunocompromised patients with hematological malignancies. Such are at increased risk complications, including hospitalization, respiratory failure, delay of anti-cancer therapies, and even death. In addition to non-pharmacologic interventions, the main strategies prevention in such vaccination pre-exposure prophylaxis.
Language: Английский
Citations
0