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

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

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Immune evasion and membrane fusion of SARS-CoV-2 XBB subvariants EG.5.1 and XBB.2.3

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

Published: Oct. 11, 2023

Immune evasion by SARS-CoV-2 paired with immune imprinting from monovalent mRNA vaccines has resulted in attenuated neutralizing antibody responses against Omicron subvariants. In this study, we characterized two new XBB variants rising circulation - EG.5.1 and XBB.2.3, for their neutralization syncytia formation. We determined the titers sera of individuals that received a bivalent vaccine booster, BA.4/5-wave infection, or XBB.1.5-wave infection. Bivalent vaccination-induced antibodies neutralized ancestral D614G efficiently, but to much less extent, XBB.2.3 variants. fact, enhanced escape appeared be driven its key defining mutation XBB.1.5-F456L. Notably, infection BA.4/5 XBB.1.5 afforded little, if any, EG.5.1, previous especially unvaccinated individuals, average near limit detection. Additionally, investigated infectivity, fusion activity, processing variant spikes HEK293T-ACE2 CaLu-3 cells found no significant differences compared earlier Overall, our findings highlight continued subvariants and, more importantly, need reformulate include better protection.

Language: Английский

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An updated atlas of antibody evasion by SARS-CoV-2 Omicron sub-variants including BQ.1.1 and XBB

Cell Reports Medicine, Journal Year: 2023, Volume and Issue: 4(4), P. 100991 - 100991

Published: March 21, 2023

Emerging Omicron sub-variants are causing global concerns, and their immune evasion should be monitored continuously. We previously evaluated the escape of BA.1, BA.1.1, BA.2, BA.3 from an atlas 50 monoclonal antibodies (mAbs), covering seven epitope classes severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain (RBD). Here, we update totally 77 mAbs against emerging including BQ.1.1 XBB find that BA.4/5, BQ.1.1, display further evasion. Besides, investigation into correlation binding neutralization reveals important role antigenic conformation in mAb functioning. Moreover, complex structures BA.2 RBD/BD-604/S304 BA.4/5 RBD/BD-604/S304/S309 elucidate molecular mechanism antibody by these sub-variants. By focusing on identified broadly potent mAbs, a general hotspot RBD, which could guide design vaccines calls for new broad-spectrum countermeasures COVID-19.

Language: Английский

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Epistasis lowers the genetic barrier to SARS-CoV-2 neutralizing antibody escape

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Jan. 19, 2023

Waves of SARS-CoV-2 infection have resulted from the emergence viral variants with neutralizing antibody resistance mutations. Simultaneously, repeated antigen exposure has generated affinity matured B cells, producing broadly receptor binding domain (RBD)-specific antibodies activity against emergent variants. To determine how might escape these antibodies, we subjected chimeric viruses encoding spike proteins ancestral, BA.1 or BA.2 to selection by 40 antibodies. We identify numerous examples epistasis, whereby in vitro selected and naturally occurring substitutions RBD epitopes that do not confer Wuhan-Hu-1 spike, so spikes. As few as 2 3 BA.5 nearly all substantial plasma most individuals. Thus, epistasis facilitates acquisition remained effective early omicron

Language: Английский

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Antigenic mapping of emerging SARS-CoV-2 omicron variants BM.1.1.1, BQ.1.1, and XBB.1

The Lancet Microbe, Journal Year: 2023, Volume and Issue: 4(5), P. e294 - e295

Published: Jan. 16, 2023

Novel SARS-CoV-2 omicron variants, including BM.1.1.1, BQ.1.1, and XBB.1, continue to emerge at an unprecedented rate, evading pre-existing immunity from vaccination previous infection. Quantifying the antigenic diversity of variants might assist in selecting future vaccine strains. To determine relationships between emerging we others1Wilks SH Mühlemann B Shen X et al.Mapping serological responses.bioRxiv. 2022; (published online July 13.) (preprint).https://doi.org/10.1101/2022.01.28.477987PubMed Google Scholar, 2Wang W Lusvarghi S Subramanian R al.Antigenic cartography well-characterized human sera shows neutralization differences based on infection history.Cell Host Microbe. 30: 1745-1758Summary Full Text PDF PubMed Scopus (1) 3van der Straten K Guerra D van Gils MJ using sequence-confirmed concern infections reveals divergence omicron.Immunity. 55: 1725-1731Summary (7) 4Mykytyn AZ Rissmann M Kok A that BA.1 BA.2 are antigenically distinct.Sci Immunol. 7eabq4450Crossref (16) Scholar used cartography, whereby multidimensional scaling is generate maps which positions antigens antiserum samples directly correspond neutralising titres. This method allows for quantification visualisation properties different simultaneously. Previously, hamster model map.4Mykytyn We now inoculated hamsters with currently dominant BA.5 variant, genetically close BA.2, differing spike amino acid sequence by only three substitutions two deletions (appendix p 1). Neutralising titres were determined all serum grown previously, along XBB.1 emerged late 2022 2). Omicron neutralised homologous virus, BQ.1.1 efficiently, whereas BM.1.1.1 was poorly neutralised. None able substantially neutralise XBB.1. Next, generated updated map available viral 3). In this map, positioned distantly pre-omicron cluster. within one unit representing a two-fold dilution neutralisation titrations. All remaining 2·3 7·0 units each other. mapped furthest variants. Similar results observed dimensions 4). The data well represented dimensions, no substantial improvement higher number 5). Two dimensional distances correlated overall there good coordination accuracy placement samples. Despite lower certainty positioning reactive heterologous present spaced, allow approximation position new (without their respective samples). post-vaccination reflected as largest reduction compared D614G variant against followed BA.1, similar levels 6). Our reveal cross-neutralisation but little BM.1.1.1. similarities thus far evidence increased bivalent vaccines, potentially due immunological imprinting.5Zou J Kurhade C Patel al.Improved Neutralization BA.4/5, BA.4.6, BA.2.75.2, BA.4/5 vaccine.bioRxiv. Nov 17.) (preprint).https://doi.org/10.1101/2022.11.17.516898Google 6Kurhade Zou Xia H al.Low BA.2.75·2, parental mRNA or BA.5-bivalent booster.Nat Med. Dec 6.)https://doi.org/10.1038/s41591-022-02162-xCrossref 7Park YJ Pinto Walls AC al.Imprinted antibody responses sublineages.Science. 378: 619-627Crossref (6) addition, these newly do not cluster other, therefore any cross-neutralise new, could be equally distant. Continuous mapping greater understanding evolutionary trajectory indicate potential candidates. publication has been corrected. corrected version first appeared thelancet.com/microbe February 7, 2023 work financially supported Health∼Holland grant LSHM19136 BLH; cofunded PPP Allowance made Health∼Holland, Top Sector Life Sciences & Health, stimulate public-private partnerships, European Union's Horizon 2020 research innovation program under 101003589 (RECoVER; MPGK) EU funding agreement 874735(VEO). BLH, RAMF, DJS, MPGK NIH/NIAID Centers Excellence Influenza Research Response contract 75N93021C00014-Icahn School Medicine Mt Sinai. MER AK contributed equally. Download .pdf (5.09 MB) Help pdf files Supplementary appendix Correction Lancet Microbe 2023; published Jan 16. https://doi.org/10.1016/S2666-5247(22)00384-6Mykytyn AZ, Rosu ME, A, al. Antigenic https://doi.org/10.1016/S2666-5247(22)00384-6—In Correspondence, second sentence fourth paragraph should have read “Despite imprinting.” There also correction appendix. Full-Text Open Access

Language: Английский

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SARS-CoV-2 Omicron variants: burden of disease, impact on vaccine effectiveness and need for variant-adapted vaccines

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: May 23, 2023

The highly transmissible Omicron (B.1.1.529) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first detected in late 2021. Initial waves were primarily made up sub-lineages BA.1 and/or BA.2, BA.4, and BA.5 subsequently became dominant mid-2022, several descendants these have since emerged. infections generally caused less disease on average than those by earlier variants concern healthy adult populations, at least, part, due to increased population immunity. Nevertheless, healthcare systems many countries, particularly with low immunity, been overwhelmed unprecedented surges prevalence during waves. Pediatric admissions also higher compared previous concern. All exhibit partial escape from wild-type (Wuhan-Hu 1) spike-based vaccine-elicited neutralizing antibodies, more enhanced immuno-evasive properties emerging over time. Evaluating vaccine effectiveness (VE) against has become challenging a complex background varying coverage, platforms, prior infection rates, hybrid Original messenger RNA booster doses substantially improved VE or BA.2 symptomatic disease. However, protection waned, reductions months after administration. While original CD8 + CD4 T-cell responses cross-recognize sub-lineages, thereby retaining outcomes, variant-adapted vaccines are required expand the breadth B-cell improve durability protection. Variant-adapted rolled out 2022 increase overall antigenically aligned immune mechanisms.

Language: Английский

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Population immunity predicts evolutionary trajectories of SARS-CoV-2

Cell, Journal Year: 2023, Volume and Issue: 186(23), P. 5151 - 5164.e13

Published: Oct. 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.

Language: Английский

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An overview of the vaccine platforms to combat COVID-19 with a focus on the subunit vaccines

Progress in Biophysics and Molecular Biology, Journal Year: 2023, Volume and Issue: 178, P. 32 - 49

Published: Feb. 20, 2023

Language: Английский

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Duration of protection of ancestral-strain monovalent vaccines and effectiveness of bivalent BA.1 boosters against COVID-19 hospitalisation in England: a test-negative case-control study

The Lancet Infectious Diseases, Journal Year: 2023, Volume and Issue: 23(11), P. 1235 - 1243

Published: July 12, 2023

Bivalent BA.1 booster vaccines were offered to adults aged 50 years or older and clinically vulnerable people as part of the 2022 autumn COVID-19 vaccination programme in England. Previously, all England had been a primary course consisting two doses either ChAdOx1-S monovalent mRNA vaccine an vaccine. We aimed estimate long-term duration protection provided by vaccines, incremental effectiveness bivalent boosters.In this test-negative case-control study, cases controls 18 identified from national data for PCR tests done hospital settings Our analysis was restricted with acute respiratory infections coded diagnosis field. Data status extracted English register linked testing data. Between June 13 Dec 25, 2022, we estimated against hospitalisation three more compared being unvaccinated, stratified age (18-64 vs ≥65 years). Sept 5, Feb 2023, (ie, addition earlier vaccines) receiving at least (when last dose 6 months ago) among older. Analyses adjusted week test, gender, age, risk group, residing care home, health social worker, Index Multiple Deprivation quintile, ethnicity, recent positivity.Our included 19 841 43 410 controls. Absolute who received plateaued after around 50% those 65 30% 18-64 years. analyses boosters 9954 39 108 Incremental peaked 53·0% (95% CI 47·9-57·5) 2-4 weeks administration, before waning 35·9% (31·4-40·1) 10 weeks.Our study provides evidence that offer moderate effective preventing time when omicron lineages circulating England.None.

Language: Английский

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Evolution of antibody immunity following Omicron BA.1 breakthrough infection

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: May 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

Language: Английский

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