SARS-CoV-2 JN.1 variant: a short review DOI Creative Commons

Sarkar Malay,

Irappa Madabhavi,

Anurag Tripathi

et al.

Monaldi Archives for Chest Disease, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 30, 2024

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a single-stranded, positive-sense RNA virus. SARS-CoV-2 virus evolving continuously, and many variants have been detected over the last few years. SARS-CoV-2, as an virus, more prone to mutating. continuous evolution of due genetic mutation recombination during genomic replication process. Recombination naturally occurring phenomenon in which two distinct viral lineages simultaneously infect same cellular entity individual. rate depends on mutation. variable among viruses, with exhibiting lower than other viruses. novel 3'-to-5' exoribonuclease proofreading machinery responsible for Infection influenza, syncytial has reported from around world period fall winter, resulting "tripledemic." JN.1 variant, evolved predecessor, omicron variant BA.2.86, currently most dominant globally. impact transmissibility, disease severity, immune evasion, diagnostic therapeutic escape will be discussed.

Language: Английский

Distinct patterns of SARS-CoV-2 BA.2.87.1 and JN.1 variants in immune evasion, antigenicity, and cell-cell fusion DOI Creative Commons

Pei Li,

Yajie Liu, Julia N. Faraone

et al.

mBio, Journal Year: 2024, Volume and Issue: 15(5)

Published: April 9, 2024

The rapid evolution of SARS-CoV-2 variants presents a constant challenge to the global vaccination effort. In this study, we conducted comprehensive investigation into two newly emerged variants, BA.2.87.1 and JN.1, focusing on their neutralization resistance, infectivity, antigenicity, cell-cell fusion, spike processing. Neutralizing antibody (nAb) titers were assessed in diverse cohorts, including individuals who received bivalent mRNA vaccine booster, patients infected during BA.2.86/JN.1-wave, hamsters vaccinated with XBB.1.5-monovalent vaccine. We found that shows much less nAb escape from WT-BA.4/5 JN.1-wave breakthrough infection sera compared JN.1 XBB.1.5. Interestingly, is more resistant by XBB.1.5-monovalent-vaccinated hamster than BA.2.86/JN.1 XBB.1.5, but efficiently neutralized class III monoclonal S309, which largely fails neutralize BA.2.86/JN.1. Importantly, exhibits higher levels fusion activity, furin cleavage efficiency Antigenically, closer ancestral BA.2 other recently Omicron subvariants Altogether, these results highlight immune properties as well biology new underscore importance continuous surveillance informed decision-making development effective vaccines.

Language: Английский

Citations

30
Recombinant XBB.1.5 boosters induce robust neutralization against KP.2- and KP.3-included JN.1 sublineages DOI Creative Commons
H. J. Yang,

Xuemei He,

Shi H

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Jan. 27, 2025

Abstract The newly emerged variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) demonstrate resistance to present therapeutic antibodies as well the capability evade vaccination-elicited antibodies. JN.1 sublineages were demonstrated one most immune-evasive variants, showing higher neutralization compared XBB.1.5. In this study, serum samples collected from adult participants including those who had gone through BA.5/BF.7, EG.5/HK.3 and XBB/JN.1 infection waves, characterized by different vaccination histories. We evaluated in these against pseudoviruses Omicron lineages. further investigated humoral immune response recombinant XBB vaccines estimated sublineages, KP.2 KP.3. Our results showed that sera previous circulating subvariant breakthrough infections exhibited low GMTs 50% all tested significantly elevated individuals received WSK-V102C or WSK-V102D boosters. Importantly, 4 months after a booster XBB.1.5, JN.1, JN.1.13, KP.3 3479, 1684, 1397, 1247 1298, with 9.86-, 9.79-, 8.73-, 8.66- 8.16-fold increase without booster, respectively, indicating boosting XBB.1.5 subunit still induced strong antibody responses sublineages. However, KP.3, revealed more than 2-fold decreases neutralizing titers suggesting enhanced evasion necessity boosters based on

Language: Английский

Citations

2
Neutralization and Stability of JN.1-derived LB.1, KP.2.3, KP.3 and KP.3.1.1 Subvariants DOI Creative Commons

Pei Li,

Julia N. Faraone, Cheng Chih Hsu

et al.

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
The rising SARS‐CoV‐2 JN.1 variant: evolution, infectivity, immune escape, and response strategies DOI Creative Commons
Yishan Lu, Danyi Ao,

Xuemei He

et al.

MedComm, Journal Year: 2024, Volume and Issue: 5(8)

Published: July 29, 2024

The JN.1 variant of COVID-19 has emerged as the dominant strain worldwide since end 2023. As a subclade BA.2.86 variant, harbors unique combination mutations inherited from lineage, notably featuring novel L455S mutation within its receptor-binding motif. This been linked to increased transmissibility and enhanced immune evasion capabilities. During rise JN.1, evidence resistance various monoclonal antibodies reduced cross-neutralization effects XBB.1.5 vaccine have observed. Although public health threat posed by appears relatively low, concerns persist regarding evolutionary trajectory under pressure. review provides comprehensive overview evolving highlighting need for continuous monitoring investigation new variants that could lead widespread infection. It assesses efficacy current vaccines therapeutics against emerging variants, particularly focusing on immunocompromised populations. Additionally, this summarizes potential advancements clinical treatments COVID-19, offering insights optimize prevention treatment strategies. thoroughly evaluates variant's impact implications future therapeutic development, contributing ongoing efforts mitigate risk virus transmission disease severity.

Language: Английский

Citations

9
SARS-CoV-2 JN.1 variant evasion of IGHV3-53/3-66 B cell germlines DOI Open Access
Ida Paciello, Giuseppe Maccari, Giulio Pierleoni

et al.

Science Immunology, Journal Year: 2024, Volume and Issue: 9(98)

Published: Aug. 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.

Language: Английский

Citations

8
Neutralization and spike stability of JN.1-derived LB.1, KP.2.3, KP.3, and KP.3.1.1 subvariants DOI Creative Commons

Pei Li,

Julia N. Faraone, Cheng Chih Hsu

et al.

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
Immune Evasion, Cell-Cell Fusion, and Spike Stability of the SARS-CoV-2 XEC Variant: Role of Glycosylation Mutations at the N-terminal Domain DOI Creative Commons

Pei Li,

Julia N. Faraone, Cheng Chih Hsu

et al.

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

Published: Nov. 13, 2024

SARS-CoV-2 continues to evolve, producing new variants that drive global COVID-19 surges. XEC, a recombinant of KS.1.1 and KP.3.3, contains T22N F59S mutations in the spike protein's N-terminal domain (NTD). The mutation, similar DelS31 mutation KP.3.1.1, introduces potential N-linked glycosylation site XEC. In this study, we examined neutralizing antibody (nAb) response effects sera from bivalent-vaccinated healthcare workers, BA.2.86/JN.1 wave-infected patients, XBB.1.5 monovalent-vaccinated hamsters, assessing responses XEC alongside D614G, JN.1, KP.3, KP.3.1.1. demonstrated significantly reduced neutralization titers across all cohorts, largely due mutation. Notably, removal sites KP.3.1.1 substantially restored nAb titers. Antigenic cartography analysis revealed be more antigenically distinct its common ancestral compared with as determining factor. Similar showed cell-cell fusion relative parental change attributed glycosylation. We also observed S1 shedding for which was reversed by ablation mutations, respectively. Molecular modeling suggests alters hydrophobic interactions adjacent protein residues, impacting both conformational stability neutralization. Overall, our findings underscore pivotal role NTD shaping biology immune escape mechanisms.

Language: Английский

Citations

6
SARS-CoV-2 Vaccines: The Advantage of Mucosal Vaccine Delivery and Local Immunity DOI Creative Commons
Joshua Tobias, Peter Steinberger,

Joy Wilkinson

et al.

Vaccines, Journal Year: 2024, Volume and Issue: 12(7), P. 795 - 795

Published: July 18, 2024

Immunity against respiratory pathogens is often short-term, and, consequently, there an unmet need for the effective prevention of such infections. One infectious disease coronavirus 19 (COVID-19), which caused by novel Beta SARS-CoV-2 that emerged around end 2019. The World Health Organization declared illness a pandemic on 11 March 2020, and since then it has killed or sickened millions people globally. development COVID-19 systemic vaccines, impressively led to significant reduction in severity, hospitalization, mortality, contained pandemic’s expansion. However, these vaccines have not been able stop virus from spreading because restricted mucosal immunity. As result, breakthrough infections frequently occurred, new strains emerging. Furthermore, will likely continue circulate like influenza virus, co-exist with humans. upper tract nasal cavity are primary sites infection thus, mucosal/nasal vaccination induce response virus’ transmission warranted. In this review, we present status both approved those under evaluation clinical trials. our approach B-cell peptide-based applied prime-boost schedule elicit

Language: Английский

Citations

5
FLip mutations (L455F + F456L) in newly emerging VOI, JN.1: Its antibody and immune escape DOI
Chiranjib Chakraborty, Manojit Bhattacharya

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 133, P. 112146 - 112146

Published: April 26, 2024

Language: Английский

Citations

4
Antigenic sin and multiple breakthrough infections drive converging evolution of COVID-19 neutralizing responses DOI Creative Commons
Ida Paciello, Giulio Pierleoni, Elisa Pantano

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(9), P. 114645 - 114645

Published: Aug. 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.

Language: Английский

Citations

4