BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection

Nature, Journal Year: 2022, Volume and Issue: 608(7923), P. 593 - 602

Published: June 17, 2022

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages BA.2.12.1, BA.4 and BA.5 exhibit higher transmissibility than the BA.2 lineage 1 . The receptor binding immune-evasion capability of these recently emerged variants require immediate investigation. Here, coupled with structural comparisons spike proteins, we show that (BA.4 are hereafter referred collectively to as BA.4/BA.5) similar affinities for angiotensin-converting enzyme (ACE2) receptor. Of note, BA.2.12.1 BA.4/BA.5 display increased evasion neutralizing antibodies compared against plasma from triple-vaccinated individuals or who developed a BA.1 infection after vaccination. To delineate underlying antibody-evasion mechanism, determined escape mutation profiles , epitope distribution 3 Omicron-neutralization efficiency 1,640 directed receptor-binding domain viral protein, including 614 isolated people had recovered infection. vaccination predominantly recalls humoral immune memory ancestral (hereafter wild-type (WT)) SARS-CoV-2 protein. resulting elicited could neutralize both WT enriched on epitopes do not bind ACE2. However, most cross-reactive evaded by mutants L452Q, L452R F486V. can also induce new clones BA.1-specific potently BA.1. Nevertheless, largely owing D405N F486V mutations, react weakly pre-Omicron variants, exhibiting narrow neutralization breadths. therapeutic bebtelovimab 4 cilgavimab 5 effectively BA.4/BA.5, whereas S371F, R408S mutations undermine broadly sarbecovirus-neutralizing antibodies. Together, our results indicate may evolve evade immunity infection, suggesting BA.1-derived vaccine boosters achieve broad-spectrum protection variants.

Language: Английский

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COVID-19 vaccine development: milestones, lessons and prospects

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: May 3, 2022

Abstract With the constantly mutating of SARS-CoV-2 and emergence Variants Concern (VOC), implementation vaccination is critically important. Existing vaccines mainly include inactivated, live attenuated, viral vector, protein subunit, RNA, DNA, virus-like particle (VLP) vaccines. Viral vector vaccines, subunit mRNA may induce additional cellular or humoral immune regulations, including Th cell responses germinal center responses, form relevant memory cells, greatly improving their efficiency. However, some be associated with complications like thrombocytopenia myocarditis, raising concerns about safety these COVID-19 Here, we systemically assess efficacy possible different effects on pregnant women, elderly, people diseases acquired immunodeficiency syndrome (AIDS), transplant recipients, cancer patients. Based current analysis, governments agencies are recommended to continue advance vaccine immunization process. Simultaneously, special attention should paid health status timely treatment complications, development, ensuring lives In addition, available measures such as mix-and-match vaccination, developing new nanoparticle optimizing adjuvant improve could considered.

Language: Английский

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Modeling transmission of SARS-CoV-2 Omicron in China

Nature Medicine, Journal Year: 2022, Volume and Issue: 28(7), P. 1468 - 1475

Published: May 10, 2022

Having adopted a dynamic zero-COVID strategy to respond SARS-CoV-2 variants with higher transmissibility since August 2021, China is now considering whether, and for how long, this policy can remain in place. The debate has thus shifted towards the identification of mitigation strategies minimizing disruption healthcare system case nationwide epidemic. To aim, we developed an age-structured stochastic compartmental susceptible-latent-infectious-removed-susceptible model transmission calibrated on initial growth phase 2022 Omicron outbreak Shanghai, project COVID-19 burden (that is, number cases, patients requiring hospitalization intensive care, deaths) under hypothetical scenarios. also considers age-specific vaccine coverage data, efficacy against different clinical endpoints, waning immunity, antiviral therapies nonpharmaceutical interventions. We find that level immunity induced by March vaccination campaign would be insufficient prevent wave result exceeding critical care capacity projected unit peak demand 15.6 times existing causing approximately 1.55 million deaths. However, estimate protecting vulnerable individuals ensuring accessibility vaccines therapies, maintaining implementation interventions could sufficient overwhelming system, suggesting these factors should points emphasis future policies.

Language: Английский

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Repeated Omicron exposures override ancestral SARS-CoV-2 immune imprinting

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

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Reduced sensitivity of SARS-CoV-2 Omicron variant to antibody neutralization elicited by booster vaccination

Cell Discovery, Journal Year: 2022, Volume and Issue: 8(1)

Published: Jan. 17, 2022

Language: Английский

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BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: May 2, 2022

Abstract SARS-CoV-2 Omicron sublineages BA.2.12.1, BA.4 and BA.5 exhibit higher transmissibility over BA.2 1 . The new variants’ receptor binding immune evasion capability require immediate investigation. Here, coupled with Spike structural comparisons, we show that BA.2.12.1 BA.4/BA.5 comparable ACE2-binding affinities to BA.2. Importantly, display stronger neutralization than against the plasma from 3-dose vaccination and, most strikingly, post-vaccination BA.1 infections. To delineate underlying antibody mechanism, determined escaping mutation profiles 2 , epitope distribution 3 efficacy of 1640 RBD-directed neutralizing antibodies (NAbs), including 614 isolated convalescents. Interestingly, infection mainly recalls wildtype-induced humoral memory. resulting elicited could neutralize both wildtype are enriched on non-ACE2-competing epitopes. However, these cross-reactive NAbs heavily escaped by L452Q, L452R F486V. can also induce clones BA.1-specific potently BA.1; nevertheless, largely BA.2/BA.4/BA.5 due D405N F486V, react weakly pre-Omicron variants, exhibiting poor breadths. As for therapeutic NAbs, Bebtelovimab 4 Cilgavimab 5 effectively BA.4/BA.5, while S371F, R408S mutations would undermine broad sarbecovirus NAbs. Together, our results indicate may evolve evade immunity infection, suggesting BA.1-derived vaccine boosters not achieve broad-spectrum protection variants.

Language: Английский

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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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Repeated Omicron exposures override ancestral SARS-CoV-2 immune imprinting

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: May 2, 2023

Abstract The continuous emergence of highly immune evasive SARS-CoV-2 variants, like XBB.1.5 1,2 and XBB.1.16 3,4 , highlights the need to update COVID-19 vaccine compositions. However, imprinting induced by wildtype (WT)-based vaccination would compromise antibody response Omicron-based boosters 5-9 . Vaccination strategies that can counter are critically needed. In this study, we investigated degree dynamics in mouse models human cohorts, especially focusing on role repeated Omicron stimulation. Our results show mice, efficacy single Omicron-boosting is heavily limited imprinting, when using variants antigenically distinct from WT, XBB, while concerning situation could be largely mitigated a second booster. Similarly, humans, found infections also alleviate WT-vaccination-induced generate high neutralizing titers against both plasma nasal mucosa. By isolating 781 RBD-targeting mAbs infection revealed double exposure alleviates generating large proportion matured potent Omicron-specific antibodies. Importantly, epitope characterization deep mutational scanning (DMS) showed these antibodies target RBD epitopes compared WT-induced antibodies, bias towards non-neutralizing observed exposures due was restored after stimulation, together leading substantial shift. Based DMS profiles, identified evolution hotspots demonstrated combinations mutations further boost XBB.1.5’s immune-evasion capability maintaining ACE2 binding affinity. findings suggest WT component should abandoned updating antigen compositions XBB lineages, those who haven’t been exposed yet receive two updated boosters.

Language: Английский

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An intranasal combination vaccine induces systemic and mucosal immunity against COVID-19 and influenza

npj Vaccines, Journal Year: 2024, Volume and Issue: 9(1)

Published: March 21, 2024

Abstract Despite prolonged surveillance and interventions, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) influenza viruses continue to pose a global health burden. Thus, we developed chimpanzee adenovirus-based combination vaccine, AdC68-HATRBD, with dual specificity against SARS-CoV-2 virus. When used as standalone intranasal immunization AdC68-HATRBD induced comprehensive potent immune responses consisting of immunoglobin (Ig) G, mucosal IgA, neutralizing antibodies, memory T cells, which protected mice from BA.5.2 pandemic H1N1 infections. heterologous booster, markedly improved protective response licensed or vaccine. Therefore, whether administered intranasally booster this vaccine is valuable strategy enhance overall efficacy by inducing robust systemic responses, thereby conferring lines immunological defenses for these two viruses.

Language: Английский

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Emerging SARS-CoV-2 variants: Why, how, and what's next?

Cell Insight, Journal Year: 2022, Volume and Issue: 1(3), P. 100029 - 100029

Published: May 2, 2022

The emergence of the SARS-CoV-2 Omicron variant poses a striking threat to human society. More than 30 mutations in Spike protein severely compromised protective immunity elicited by either vaccination or prior infection. persistent viral evolutionary trajectory generates Omicron-associated lineages, such as BA.1 and BA.2. Moreover, virus recombination upon Delta co-infections has been reported lately, although impact remains be assessed. This minireview summarizes characteristics, evolution mutation control, immune evasion mechanisms variants, which will helpful for in-depth understanding variants policy-making related COVID-19 pandemic control.

Language: Английский

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