Imprinted SARS-CoV-2 humoral immunity induces convergent Omicron RBD evolution

Nature, Год журнала: 2022, Номер unknown

Опубликована: Дек. 19, 2022

Abstract Continuous evolution of Omicron has led to a rapid and simultaneous emergence numerous variants that display growth advantages over BA.5 (ref. 1 ). Despite their divergent evolutionary courses, mutations on receptor-binding domain (RBD) converge several hotspots. The driving force destination such sudden convergent its effect humoral immunity remain unclear. Here we demonstrate these can cause evasion neutralizing antibody drugs convalescent plasma, including those from breakthrough infection, while maintaining sufficient ACE2-binding capability. BQ.1.1.10 (BQ.1.1 + Y144del), BA.4.6.3, XBB CH.1.1 are the most antibody-evasive strains tested. To delineate origin evolution, determined escape mutation profiles neutralization activity monoclonal antibodies isolated individuals who had BA.2 infections 2,3 . Owing immune imprinting, especially infection reduced diversity binding sites increased proportions non-neutralizing clones, which, in turn, focused pressure promoted RBD. Moreover, show RBD could be accurately inferred by deep mutational scanning 4,5 , trends BA.2.75 subvariants well foreseen through constructed pseudovirus mutants. These results suggest current herd vaccine boosters may not efficiently prevent variants.

Язык: Английский

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Imprinted SARS-CoV-2 humoral immunity induces convergent Omicron RBD evolution

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2022, Номер unknown

Опубликована: Сен. 16, 2022

Abstract Continuous evolution of Omicron has led to a rapid and simultaneous emergence numerous variants that display growth advantages over BA. 5. Despite their divergent evolutionary courses, mutations on receptor-binding domain (RBD) converge several hotspots. The driving force destination such convergent its impact humoral immunity remain unclear. Here, we demonstrate these can cause striking evasion neutralizing antibody (NAb) drugs convalescent plasma, including those from BA.5 breakthrough infection, while maintaining sufficient ACE2 binding capability. BQ.1.1.10, BA.4.6.3, XBB, CH. 1.1 are the most antibody-evasive strain tested, even exceeding SARS-CoV-1 level. To delineate origin evolution, determined escape mutation profiles neutralization activity monoclonal antibodies (mAbs) isolated BA.2 breakthrough-infection convalescents. Importantly, due immune imprinting, especially infection caused significant reductions in epitope diversity NAbs increased proportion non-neutralizing mAbs, which turn concentrated pressure promoted evolution. Moreover, showed RBD could be accurately inferred by integrated deep mutational scanning (DMS) profiles, trends BA.2.75/BA.5 subvariants well-simulated through constructed pseudovirus mutants. Together, our results suggest current herd vaccine boosters may not provide good protection against infection. Broad-spectrum SARS-CoV-2 vaccines NAb development should highly prioritized, mutants help examine effectiveness advance.

Язык: Английский

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Enhanced evasion of neutralizing antibody response by Omicron XBB.1.5, CH.1.1, and CA.3.1 variants

Cell Reports, Год журнала: 2023, Номер 42(5), С. 112443 - 112443

Опубликована: Апрель 18, 2023

Omicron subvariants continuingly challenge current vaccination strategies. Here, we demonstrate nearly complete escape of the XBB.1.5, CH.1.1, and CA.3.1 variants from neutralizing antibodies stimulated by three doses mRNA vaccine or BA.4/5 wave infection, but neutralization is rescued a BA.5-containing bivalent booster. CH.1.1 show strong immune monoclonal antibody S309. Additionally, spike proteins exhibit increased fusogenicity enhanced processing compared with BA.2. Homology modeling reveals key roles G252V F486P in resistance also enhancing receptor binding. Further, K444T/M L452R likely drive class II antibodies, whereas R346T G339H mutations could confer these two to S309-like antibodies. Overall, our results support need for administration continued surveillance subvariants.

Язык: Английский

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Mapping SARS-CoV-2 antigenic relationships and serological responses

Science, Год журнала: 2023, Номер 382(6666)

Опубликована: Окт. 6, 2023

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, multiple variants escaping preexisting immunity emerged, causing reinfections of previously exposed individuals. Here, we used antigenic cartography to analyze patterns cross-reactivity among 21 and 15 groups human sera obtained after primary infection with 10 different or messenger RNA (mRNA)–1273 mRNA-1273.351 vaccination. We found differences pre-Omicron caused by substitutions at spike-protein positions 417, 452, 484, 501. Quantifying changes in response breadth over time additional vaccine doses, our results show largest increase between 4 weeks >3 months a second dose. immunodominance spike regions, depending on variant an individual was first to, implications for risk assessment vaccine-strain selection.

Язык: 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, Год журнала: 2023, Номер 14

Опубликована: Май 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.

Язык: Английский

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Mapping SARS-CoV-2 antigenic relationships and serological responses

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2022, Номер unknown

Опубликована: Янв. 28, 2022

During the SARS-CoV-2 pandemic, multiple variants escaping pre-existing immunity emerged, causing concerns about continued protection. Here, we use antigenic cartography to analyze patterns of cross-reactivity among a panel 21 and 15 groups human sera obtained following primary infection with 10 different or after mRNA-1273 mRNA-1273.351 vaccination. We find differences pre-Omicron caused by substitutions at spike protein positions 417, 452, 484, 501. Quantifying changes in response breadth over time additional vaccine doses, our results show largest increase between 4 weeks >3 months post-2nd dose. immunodominance regions depending on variant an individual was first exposed to, implications for risk assessment strain selection.

Язык: Английский

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Low levels of neutralizing antibodies against XBB Omicron subvariants after BA.5 infection

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Июнь 19, 2023

Abstract The COVID-19 response strategies in Chinese mainland were recently adjusted due to the reduced pathogenicity and enhanced infectivity of Omicron subvariants. In Chengdu, China, an infection wave was predominantly induced by BA.5 subvariant. It is crucial determine whether hybrid anti-SARS-CoV-2 immunity following infection, coupled with a variety immune background, sufficient shape responses against newly emerged subvariants, especially for XBB lineages. To investigate this, we collected serum nasal swab samples from 108 participants who had been infected this wave, evaluated neutralization pseudoviruses. Our results showed that convalescent sera individuals, regardless vaccination history, remarkably compromised capacities XBB.1.5 Although post-vaccination breakthrough slightly elevated plasma neutralizing antibodies part pseudoviruses, activities impaired Furthermore, analyzed impacts number vaccinations, age, sex on humoral cellular after infection. findings suggest lineages elicited current are remained at low levels, indicating urgent need development next-generation vaccines designed based sub-lineages other future variants.

Язык: Английский

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Hybrid Immunity to SARS-CoV-2 from Infection and Vaccination—Evidence Synthesis and Implications for New COVID-19 Vaccines

Biomedicines, Год журнала: 2023, Номер 11(2), С. 370 - 370

Опубликована: Янв. 27, 2023

COVID-19 has taken a severe toll on the global population through infections, hospitalizations, and deaths. Elucidating SARS-CoV-2 infection-derived immunity led to development of multiple effective vaccines their implementation into mass-vaccination programs worldwide. After ~3 years, substantial proportion human possesses from infection and/or vaccination. With waning immune protection over time against emerging variants, it is essential understand duration protection, breadth coverage, effects reinfection. This targeted review summarizes available research literature infection-derived, vaccination-elicited, hybrid immunity. Infection-derived shown 93-100% outcomes for up 8 months, but reinfection observed with some virus variants. Vaccination elicits high levels neutralizing antibodies CD4+ CD8+ T-cell responses. Hybrid enables strong, broad responses, high-quality memory B cells generated at 5- 10-fold higher levels, versus or vaccination alone symptomatic disease lasting 6-8 months. evolution more transmissible immunologically divergent variants necessitated updating vaccines. To ensure continued regulators vaccine technical committees recommend variant-specific bivalent

Язык: Английский

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Immune evasion of neutralizing antibodies by SARS-CoV-2 Omicron

Cytokine & Growth Factor Reviews, Год журнала: 2023, Номер 70, С. 13 - 25

Опубликована: Март 5, 2023

Язык: Английский

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Previous immunity shapes immune responses to SARS-CoV-2 booster vaccination and Omicron breakthrough infection risk

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

Опубликована: Сен. 12, 2023

The heterogeneity of the SARS-CoV-2 immune responses has become considerably more complex over time and diverse imprinting is observed in vaccinated individuals. Despite vaccination, following emergence Omicron variant, some individuals appear susceptible to primary infections reinfections than others, underscoring need elucidate how are influenced by previous vaccination. IgG, IgA, neutralizing antibodies T-cell 1,325 (955 which were infection-naive) investigated before after three doses BNT162b2 vaccine, examining their relation breakthrough context Omicron. Our study shows that both humoral cellular vaccination generally higher infection compared infection-naive. Notably, viral exposure was crucial achieving a robust IgA response. Individuals with lower antibody postvaccination had significantly risk reinfection future infections. This not for responses. A subsequent dampened infection, consistent imprinting. These results underscore significant impact hybrid immunity general, particularly even revaccination, importance preventing

Язык: Английский

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