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

Repeated Omicron exposures override ancestral SARS-CoV-2 immune imprinting DOI Creative Commons
Ayijiang Yisimayi,

Weiliang Song,

Jing Wang

et al.

Nature, Journal Year: 2023, Volume and Issue: 625(7993), P. 148 - 156

Published: Nov. 22, 2023

Abstract The continuing emergence of SARS-CoV-2 variants highlights the need to update COVID-19 vaccine compositions. However, immune imprinting induced by vaccination based on ancestral (hereafter referred as WT) strain would compromise antibody response Omicron-based boosters 1–5 . Vaccination strategies counter are critically needed. Here we investigated degree and dynamics in mouse models human cohorts, especially focusing role repeated Omicron stimulation. In mice, efficacy single boosting is heavily limited when using that antigenically distinct from WT—such XBB variant—and this concerning situation could be mitigated a second booster. Similarly, humans, infections alleviate WT vaccination-induced generate broad neutralization responses both plasma nasal mucosa. Notably, deep mutational scanning-based epitope characterization 781 receptor-binding domain (RBD)-targeting monoclonal antibodies isolated infection revealed double exposure induce large proportion matured Omicron-specific have RBD epitopes WT-induced antibodies. Consequently, was largely mitigated, bias towards non-neutralizing observed exposures restored. On basis scanning profiles, identified evolution hotspots XBB.1.5 demonstrated these mutations further boost immune-evasion capability while maintaining high ACE2-binding affinity. Our findings suggest component should abandoned updating vaccines, individuals without prior receive two updated boosters.

Language: Английский

Citations

162
Distinct evolution of SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 lineages combining increased fitness and antibody evasion DOI Creative Commons
Delphine Planas, Isabelle Staropoli, Vincent Michel

et al.

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

Published: March 13, 2024

Abstract The unceasing circulation of SARS-CoV-2 leads to the continuous emergence novel viral sublineages. Here, we isolate and characterize XBB.1, XBB.1.5, XBB.1.9.1, XBB.1.16.1, EG.5.1.1, EG.5.1.3, XBF, BA.2.86.1 JN.1 variants, representing >80% circulating variants in January 2024. XBB subvariants carry few but recurrent mutations spike, whereas harbor >30 additional changes. These replicate IGROV-1 no longer Vero E6 are not markedly fusogenic. They potently infect nasal epithelial cells, with EG.5.1.3 exhibiting highest fitness. Antivirals remain active. Neutralizing antibody (NAb) responses from vaccinees BA.1/BA.2-infected individuals lower compared BA.1, without major differences between variants. An breakthrough infection enhances NAb against both BA.2.86 displays affinity ACE2 higher immune evasion properties BA.2.86.1. Thus, while distinct, evolutionary trajectory these combines increased fitness evasion.

Language: Английский

Citations

141
SARS-CoV-2 BA.2.86 enters lung cells and evades neutralizing antibodies with high efficiency DOI Creative Commons
Lu Zhang,

Amy Kempf,

Inga Nehlmeier

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(3), P. 596 - 608.e17

Published: Jan. 8, 2024

Language: Английский

Citations

81
Convergent evolution of SARS-CoV-2 XBB lineages on receptor-binding domain 455–456 synergistically enhances antibody evasion and ACE2 binding DOI Creative Commons
Fanchong Jian, Leilei Feng, Sijie Yang

et al.

PLoS Pathogens, Journal Year: 2023, Volume and Issue: 19(12), P. e1011868 - e1011868

Published: Dec. 20, 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) XBB lineages have achieved dominance worldwide and keep on evolving. Convergent evolution of the receptor-binding domain (RBD) L455F F456L is observed, resulting in variants with substantial growth advantages, such as EG.5, FL.1.5.1, XBB.1.5.70, HK.3. Here, we show that neutralizing antibody (NAb) evasion drives convergent F456L, while epistatic shift caused by enables subsequent convergence through ACE2 binding enhancement further immune evasion. evade RBD-targeting Class 1 public NAbs, reducing neutralization efficacy breakthrough infection (BTI) reinfection convalescent plasma. Importantly, single substitution significantly dampens receptor binding; however, combination forms an adjacent residue flipping, which leads to enhanced NAbs resistance affinity. The perturbed mode exceptional NAb evasion, revealed structural analyses. Our results indicate flexibility contributed epistasis cannot be underestimated, potential SARS-CoV-2 RBD remains high.

Language: Английский

Citations

76
Persistent immune imprinting occurs after vaccination with the COVID-19 XBB.1.5 mRNA booster in humans DOI Creative Commons
M. Alejandra Tortorici, Amin Addetia,

Albert J. Seo

et al.

Immunity, Journal Year: 2024, Volume and Issue: 57(4), P. 904 - 911.e4

Published: March 14, 2024

Immune imprinting describes how the first exposure to a virus shapes immunological outcomes of subsequent exposures antigenically related strains. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Omicron breakthrough infections and bivalent COVID-19 vaccination primarily recall cross-reactive memory B cells induced by prior Wuhan-Hu-1 spike mRNA rather than priming Omicron-specific naive cells. These findings indicate that immune occurs after repeated exposures, but whether it can be overcome remains unclear. To understand persistence imprinting, we investigated plasma antibody responses administration updated XBB.1.5 vaccine booster. We showed booster elicited neutralizing against current variants were dominated pre-existing previously spike. Therefore, persists multiple spikes through infection, including post vaccination, which will need considered guide future vaccination.

Language: Английский

Citations

62
Spike deep mutational scanning helps predict success of SARS-CoV-2 clades DOI Creative Commons
Bernadeta Dadonaite,

Jack Brown,

Teagan McMahon

et al.

Nature, Journal Year: 2024, Volume and Issue: 631(8021), P. 617 - 626

Published: July 3, 2024

SARS-CoV-2 variants acquire mutations in the spike protein that promote immune evasion

Language: Английский

Citations

57
Humoral and cellular immune responses following BNT162b2 XBB.1.5 vaccination DOI Open Access
Metodi V. Stankov, Markus Hoffmann,

Rodrigo Gutierrez Jauregui

et al.

The Lancet Infectious Diseases, Journal Year: 2023, Volume and Issue: 24(1), P. e1 - e3

Published: Nov. 20, 2023

Language: Английский

Citations

54
Less neutralization evasion of SARS-CoV-2 BA.2.86 than XBB sublineages and CH.1.1 DOI Creative Commons
Yanping Hu, Jing Zou, Chaitanya Kurhade

et al.

Emerging Microbes & Infections, Journal Year: 2023, Volume and Issue: 12(2)

Published: Oct. 12, 2023

The highly mutated BA.2.86, with over 30 spike protein mutations in comparison to Omicron BA.2 and XBB.1.5 variants, has raised concerns about its potential evade COVID-19 vaccination or prior SARS-CoV-2 infection-elicited immunity. In this study, we employ a live neutralization assay compare the evasion ability of BA.2.86 other emerged subvariants, including BA.2-derived CH.1.1, Delta-Omicron recombinant XBC.1.6, XBB descendants XBB.1.5, XBB.1.16, XBB.2.3, EG.5.1 FL.1.5.1. Our results show that is less evasive than sublineages. EG.5.1, FL.1.5.1 continue significantly induced by parental mRNA vaccine BA.5 Bivalent booster. Notably, when compared more recent descendants, particularly display increased resistance neutralization. Among all tested CH.1.1 exhibits greatest evasion. contrast, XBC.1.6 shows slight reduction but remains comparably sensitive BA.5. Furthermore, XBB.1.5-breakthrough infection enhances breadth potency cross-neutralization. These findings reinforce expectation upcoming would likely boost currently circulating while also underscoring critical importance ongoing surveillance monitor evolution immune variants.

Language: Английский

Citations

48
Immunological imprinting shapes the specificity of human antibody responses against SARS-CoV-2 variants DOI
Timothy S. Johnston,

Shuk Hang Li,

Mark M. Painter

et al.

Immunity, Journal Year: 2024, Volume and Issue: 57(4), P. 912 - 925.e4

Published: March 14, 2024

Language: Английский

Citations

39
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

34