Convergent evolution of SARS-CoV-2 XBB lineages on receptor-binding domain 455–456 synergistically enhances antibody evasion and ACE2 binding

PLoS Pathogens, Год журнала: 2023, Номер 19(12), С. e1011868 - e1011868

Опубликована: Дек. 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.

Язык: Английский

---

Enhanced transmissibility of XBB.1.5 is contributed by both strong ACE2 binding and antibody evasion

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Янв. 3, 2023

Abstract SARS-CoV-2 recombinant subvariant XBB.1.5 is growing rapidly in the United States, carrying an additional Ser486Pro substitution compared to XBB.1 and outcompeting BQ.1.1 other XBB sublineages. The underlying mechanism for such high transmissibility remains unclear. Here we show that exhibits a substantially higher hACE2-binding affinity XBB/XBB.1. Convalescent plasma samples from BA.1, BA.5, BF.7 breakthrough infection are significantly evaded by both XBB.1.5, with displaying slightly weaker immune evasion capability than XBB.1. Evusheld Bebtelovimab could not neutralize XBB.1/XBB.1.5, while Sotrovimab weakly reactive notably, SA55 still highly effective. fact showed comparable antibody but distinct suggests enhanced receptor-binding would indeed lead growth advantages. strong hACE2 binding of also enable its tolerance further escape mutations, which should be closely monitored.

Язык: Английский

---

Profound neutralization evasion and augmented host cell entry are hallmarks of the fast-spreading SARS-CoV-2 lineage XBB.1.5

Cellular and Molecular Immunology, Год журнала: 2023, Номер 20(4), С. 419 - 422

Опубликована: Март 3, 2023

Since late 2022, the share of infections caused by SARS-CoV-2 lineage XBB.1.5has gradually increased in United States, resulting XBB.1.5becoming dominating States and a similar trend is likely to soon take place also European countries.However, information on virological properties XBB.1.5 scarce.Here, we conducted an initial assessment XBB.1.5lineage.The XBB possesses extraordinarily high capacity for antibody evasion due its unique set S protein mutations [1][2][3][4].However, this trait may have come at cost moderately reduced host cell entry efficiency as suggested recent vitro data [1,5], which explain why sublineages only accounted small proportion total several countries (except India) so far (Fig. 1a).Recently, has changed where sublineage since XBB.1.5now represents 1a).Moreover, although being presently detected low frequencies only, increase XBB.1.5-relatedinfections observed 1a).The XBB.1.5S differs one mutation (S486P) from parental XBB.1 lineage, located receptor-binding domain (RBD) 1b).Thus, it affect transmissibility modulating efficiency, alter sensitivity antibody-mediated neutralization.Here, performed XBB.1.5lineage neutralization, using protein-bearing pseudovirus particles (pp), are suitable model system analysis neutralization [6].Particles pseudotyped with ancestral B.1 (B.1 pp ) or Omicron BA.4/BA.5 (identical amino acid level, BA.4-5 ), BQ.1.1 (BQ.1.1 (XBB.1 were used comparison.First, compared line tropism different pseudoviruses.As expected, displayed augmented most lines tested exception

Язык: Английский

---

Spike deep mutational scanning helps predict success of SARS-CoV-2 clades

Nature, Год журнала: 2024, Номер 631(8021), С. 617 - 626

Опубликована: Июль 3, 2024

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

Язык: Английский

---

Immune evasion and ACE2 binding affinity contribute to SARS-CoV-2 evolution

Nature Ecology & Evolution, Год журнала: 2023, Номер 7(9), С. 1457 - 1466

Опубликована: Июль 13, 2023

Язык: Английский

---

Population immunity predicts evolutionary trajectories of SARS-CoV-2

Cell, Год журнала: 2023, Номер 186(23), С. 5151 - 5164.e13

Опубликована: Окт. 23, 2023

The large-scale evolution of the SARS-CoV-2 virus has been marked by rapid turnover genetic clades. New variants show intrinsic changes, notably increased transmissibility, and antigenic changes that reduce cross-immunity induced previous infections or vaccinations. How this functional variation shapes global remained unclear. Here, we establish a predictive fitness model for integrates selection. is informed tracking time-resolved sequence data, epidemiological records, cross-neutralization data viral variants. Our inference shows immune pressure, including contributions vaccinations infections, become dominant force driving recent SARS-CoV-2. can serve continued surveillance in two ways. First, it successfully predicts short-term circulating strains flags emerging likely to displace previously predominant variant. Second, profiles successful escape prior their emergence.

Язык: Английский

---

Evolution of antibody immunity following Omicron BA.1 breakthrough infection

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

Опубликована: Май 12, 2023

Understanding the longitudinal dynamics of antibody immunity following heterologous SAR-CoV-2 breakthrough infection will inform development next-generation vaccines. Here, we track SARS-CoV-2 receptor binding domain (RBD)-specific responses up to six months Omicron BA.1 in mRNA-vaccinated individuals. Cross-reactive serum neutralizing and memory B cell (MBC) decline by two- four-fold through study period. Breakthrough elicits minimal de novo BA.1-specific but drives affinity maturation pre-existing cross-reactive MBCs toward BA.1, which translates into enhanced breadth activity across other variants. Public clones dominate response at both early late time points breakthough infection, their escape mutation profiles predict newly emergent sublineages, suggesting that convergent continue shape evolution. While is limited our relatively small cohort size, these results suggest variant exposure evolution memory, supporting continued variant-based

Язык: Английский

---

Mutations in the SARS-CoV-2 spike receptor binding domain and their delicate balance between ACE2 affinity and antibody evasion

Protein & Cell, Год журнала: 2024, Номер 15(6), С. 403 - 418

Опубликована: Март 4, 2024

Intensive selection pressure constrains the evolutionary trajectory of SARS-CoV-2 genomes and results in various novel variants with distinct mutation profiles. Point mutations, particularly those within receptor binding domain (RBD) spike (S) protein, lead to functional alteration both engagement monoclonal antibody (mAb) recognition. Here, we review data RBD point mutations possessed by major discuss their individual effects on ACE2 affinity immune evasion. Many single amino acid substitutions epitopes crucial for evasion capacity may conversely weaken affinity. However, this weakened effect could be largely compensated specific epistatic such as N501Y, thus maintaining overall protein all variants. The predominant direction evolution lies neither promoting nor evading mAb neutralization but a delicate balance between these two dimensions. Together, interprets how efficiently resist meanwhile is maintained, emphasizing significance comprehensive assessment mutations.

Язык: Английский

---

Evolving antibody response to SARS-CoV-2 antigenic shift from XBB to JN.1

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Апрель 22, 2024

Abstract The continuous evolution of SARS-CoV-2, particularly the emergence BA.2.86/JN.1 lineage replacing XBB lineages, necessitates re-evaluation current vaccine compositions. Here, we provide a comprehensive analysis humoral immune response to and JN.1 human exposures, emphasizing need for JN.1-lineage-based boosters. We demonstrate antigenic distinctiveness lineages in SARS-CoV-2-naive individuals but not those with prior vaccinations or infections, infection elicits superior plasma neutralization titers against its subvariants. highlight strong evasion receptor binding capability KP.3, supporting foreseeable prevalence. Extensive BCR repertoire, isolating ∼2000 RBD-specific monoclonal antibodies (mAbs) their targeting epitopes characterized by deep mutational scanning (DMS), underscores systematic superiority JN.1-elicited memory B cells (MBCs). Notably, Class 1 IGHV3-53/3-66-derived neutralizing (NAbs) contribute majorly within wildtype (WT)-reactive NAbs JN.1. However, KP.2 KP.3 evade substantial subset them, even induced JN.1, advocating booster updates optimized enrichment. JN.1-induced Omicron-specific also high potency across all Omicron lineages. Escape hotspots these have mainly been mutated RBD, resulting higher barrier escape, considering probable recovery previously escaped NAbs. Additionally, prevalence broadly reactive IGHV3-53/3-66- encoding MBCs, competing suggests inhibitory role on de novo activation naive cells, potentially explaining heavy imprinting mRNA-vaccinated individuals. These findings delineate evolving antibody shift from importance developing lineage, especially KP.3-based boosters, enhance immunity future SARS-CoV-2 variants.

Язык: Английский

---

A unified evolution-driven deep learning framework for virus variation driver prediction

Nature Machine Intelligence, Год журнала: 2025, Номер unknown

Опубликована: Янв. 17, 2025

Язык: Английский

---