Neutralizing immunity in vaccine breakthrough infections from the SARS-CoV-2 Omicron and Delta variants

Cell, Год журнала: 2022, Номер 185(9), С. 1539 - 1548.e5

Опубликована: Март 18, 2022

Язык: Английский

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Omicron BA.4/BA.5 escape neutralizing immunity elicited by BA.1 infection

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Авг. 10, 2022

SARS-CoV-2 Omicron (B.1.1.529) BA.4 and BA.5 sub-lineages, first detected in South Africa, have changes relative to BA.1 including substitutions the spike receptor binding domain. Here we isolated live viruses measured BA.4/BA.5 neutralization elicited by infection either absence or presence of previous vaccination as well from without infection. In BA.1-infected unvaccinated individuals, declines 7.6-fold for 7.5-fold BA.5. vaccinated individuals with subsequent infection, decreases 3.2-fold 2.6-fold The fold-drop versus ancestral virus this group is 4.0-fold BA.1, 12.9-fold BA.4, 10.3-fold contrast, escape similar immunity: 19.8-fold 19.6-fold 20.9-fold These results show considerable immunity which moderated may indicate that strongest selective advantage evading unvaccinated, infected individuals.

Язык: Английский

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Recall of preexisting cross-reactive B cell memory after Omicron BA.1 breakthrough infection

Science Immunology, Год журнала: 2022, Номер 7(73)

Опубликована: Май 12, 2022

Understanding immune responses after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection will facilitate the development of next-generation vaccines. Here, we profiled spike (S)–specific B cell Omicron/BA.1 in messenger RNA–vaccinated donors. The antibody response was characterized by high levels somatic hypermutation and a bias toward recognition ancestral SARS-CoV-2 strains, suggesting early activation vaccine-induced memory cells. BA.1 induced shift immunodominance hierarchy from S2 subunit, which is highly conserved across variants concern (VOCs), antigenically variable receptor binding domain (RBD). A large proportion RBD-directed neutralizing antibodies isolated donors displayed convergent sequence features broadly recognized VOCs. Together, these findings provide insights into role preexisting immunity shaping to heterologous variant exposure.

Язык: Английский

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Impact of antigenic evolution and original antigenic sin on SARS-CoV-2 immunity

Journal of Clinical Investigation, Год журнала: 2023, Номер 133(1)

Опубликована: Янв. 2, 2023

Infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and vaccinations targeting the spike protein (S) offer protective immunity against disease 2019 (COVID-19). This may further be shaped by cross-reactivity common cold coronaviruses. Mutations arising in S that are associated altered intrinsic virus properties immune escape result continued circulation of SARS-CoV-2 variants. Potentially, vaccine updates will required to protect future variants concern, as for influenza. To potent protection variants, these second-generation vaccines need redirect epitopes not merely boost toward conserved domains preimmune individuals. For influenza, efficacy repeated vaccination is hampered original antigenic sin, an attribute memory leads greater induction antibodies specific first-encountered variant immunogen compared subsequent In this Review, recent findings on sin discussed context evolution. Unanswered questions directions highlighted, emphasis impact outcome design.

Язык: Английский

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Omicron sub-lineages BA.4/BA.5 escape BA.1 infection elicited neutralizing immunity

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

Опубликована: Май 1, 2022

The SARS-CoV-2 Omicron (B.1.1.529) variant first emerged as the BA.1 sub-lineage, with extensive escape from neutralizing immunity elicited by previous infection other variants, vaccines, or combinations of both 1,2 . Two new sub-lineages, BA.4 and BA.5, are now emerging in South Africa changes relative to BA.1, including L452R F486V mutations spike receptor binding domain. We isolated live BA.5 viruses tested them against participants who were Omicron/BA.1 infected but unvaccinated (n=24) vaccinated Pfizer BNT162b2 Johnson Ad26.CoV.2S breakthrough (n=15). In individuals, FRNT 50 , inverse dilution for 50% neutralization, declined 275 36 37 a 7.6 7.5-fold drop, respectively. breakthroughs, 507 158 (3.2-fold) 198 (2.6-fold). Absolute neutralization levels about 5-fold higher this group versus participants. observed is more moderate than 1,3 However, low absolute particularly group, unlikely protect well symptomatic 4 .This may indicate that, based on escape, have potential result wave.

Язык: Английский

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Omicron infection enhances Delta antibody immunity in vaccinated persons

Nature, Год журнала: 2022, Номер 607(7918), С. 356 - 359

Опубликована: Май 6, 2022

Abstract The extent to which Omicron infection 1–9 , with or without previous vaccination, elicits protection against the previously dominant Delta (B.1.617.2) variant is unclear. Here we measured neutralization capacity variants of severe acute respiratory syndrome coronavirus 2 in 39 individuals South Africa infected sublineage BA.1 starting at a median 6 (interquartile range 3–9) days post symptom onset and continuing until last follow-up sample available, 23 19–27) symptoms allow BA.1-elicited neutralizing immunity time develop. Fifteen participants were vaccinated Pfizer's BNT162b2 Johnson & Johnson's Ad26.CoV2.S had breakthrough infections, 24 unvaccinated. increased from geometric mean 50% focus reduction test titre 42 enrolment 575 point (13.6-fold) 46 272 (6.0-fold) unvaccinated participants. virus also increased, 192 1,091 (5.7-fold) 28 91 (3.0-fold) At point, low absolute levels for non-BA.1 viruses 2.2-fold lower neutralization, 12.0-fold 9.6-fold Beta 17.9-fold ancestral 4.8-fold BA.2 relative BA.1. These results indicate that hybrid formed by vaccination should be protective other variants. By contrast, alone offers limited cross-protection despite moderate enhancement.

Язык: Английский

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Recent developments in the immunopathology of COVID‐19

Allergy, Год журнала: 2022, Номер 78(2), С. 369 - 388

Опубликована: Ноя. 24, 2022

Abstract There has been an important change in the clinical characteristics and immune profile of Coronavirus disease 2019 (COVID‐19) patients during pandemic thanks to extensive vaccination programs. Here, we highlight recent studies on COVID‐19, from immunological protective risk factors for severity mortality COVID‐19. The efficacy COVID‐19 vaccines potential allergic reactions after administration are also discussed. occurrence new variants concerns such as Omicron BA.2, BA.4, BA.5 global have changed scenario Multisystem inflammatory syndrome children (MIS‐C) may cause severe heterogeneous but with a lower rate. Perturbations immunity T cells, B mast well autoantibodies metabolic reprogramming contribute long‐term symptoms is conflicting evidence about whether atopic diseases, asthma rhinitis, associated susceptibility better outcomes At beginning pandemic, European Academy Allergy Clinical Immunology (EAACI) developed guidelines that provided timely information management diseases preventive measures reduce transmission clinics. distribution emerging acute respiratory coronavirus 2 (SARS‐CoV‐2) reduced pathogenic dramatically decreased morbidity, severity, Nevertheless, breakthrough infection remains challenge control. Hypersensitivity (HSR) low compared other vaccines, these were addressed EAACI statements indications reactions, including anaphylaxis vaccines. We gained depth knowledge experience over years since start yet full eradication SARS‐CoV‐2 not horizon. Novel strategies warranted prevent high‐risk groups, development MIS‐C long

Язык: Английский

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Risk of SARS-CoV-2 reinfection during multiple Omicron variant waves in the UK general population

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Фев. 2, 2024

SARS-CoV-2 reinfections increased substantially after Omicron variants emerged. Large-scale community-based comparisons across multiple waves of reinfection characteristics, risk factors, and protection afforded by previous infection vaccination, are limited. Here we studied ~45,000 from the UK's national COVID-19 Infection Survey quantified in waves, including those driven BA.1, BA.2, BA.4/5, BQ.1/CH.1.1/XBB.1.5 variants. Reinfections were associated with lower viral load percentages self-reporting symptoms compared first infections. Across estimated against was significantly higher previously infected more recent than earlier variants, even at same time infection. Estimated decreased over most if this or penultimate variant (generally within preceding year). Those 14-180 days receiving their vaccination had a >180 vaccination. Reinfection independently aged 30-45 years, either low high Overall, is high, but severity infections; both evolution waning immunity reinfection.

Язык: Английский

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Breakthrough infections after COVID-19 vaccination: Insights, perspectives and challenges

Metabolism Open, Год журнала: 2022, Номер 14, С. 100180 - 100180

Опубликована: Март 17, 2022

Vaccination programs against SARS-CoV-2 constitute the mainstay of public health interventions global COVID-19 pandemic. Currently available vaccines have shown 90% or better rates protection severe disease and mortality. Barely a year after became available, Omicron variant its unprecedented speed transmission has posed new challenge. Overall, presents increased immune escape, transmissibility, decreased pathogenicity. Vaccines do not offer full acquisition, since "breakthrough" infections may occur in fully vaccinated individuals, who turn spread virus to others. Breakthrough be causally related viral profile (viral load, incubation period, pathogenicity, evasion), immunity characteristics (mucosal versus systemic immunity, duration etc.), host determinants (age, comorbidities, status, immunosuppressive drugs) vaccination properties (platform, antigen dose, dose number, interval, route administration). Determining rate breakthrough challenging necessitates conduction population-based studies regarding vaccine effectiveness as well neutralizing antibody testing, surrogate protection. In this review, we analyze causes infections, their clinical consequences (severity infection transmission), methods determining incidence challenges perspectives. Long COVID multi-inflammatory syndrome adolescents significantly reduced infections. The need for universal pancoranavirus that would aim at protecting plethora variants emerging is discussed. Finally, novel strategies, such nasal vaccines, confer robust mucosal protection, reducing efficiently transmission.

Язык: Английский

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Omicron BA.2 breakthrough infection enhances cross-neutralization of BA.2.12.1 and BA.4/BA.5

Science Immunology, Год журнала: 2022, Номер 7(77)

Опубликована: Сен. 20, 2022

BNT162b2-vaccinated individuals after Omicron BA.1 breakthrough infection have strong serum-neutralizing activity against BA.1, BA.2, and previous SARS-CoV-2 variants of concern (VOCs) yet less the highly contagious sublineages BA.4 BA.5 that displaced variants. Because latter are derived from we characterized COVID-19 mRNA vaccine triple-immunized who experienced BA.2 infection. We demonstrate sera these broadly neutralizing VOCs all tested sublineages, including BA.2-derived BA.2.12.1 BA.4/BA.5. Furthermore, applying antibody depletion, showed neutralization BA.4/BA.5 by convalescent is driven to a considerable extent antibodies targeting N-terminal domain (NTD) spike glycoprotein. However, depends exclusively on receptor binding (RBD). These findings suggest exposure in contrast glycoprotein, triggers substantial NTD-specific recall responses vaccinated thereby enhances sublineages. Given current epidemiology with predominance such as rapidly ongoing evolution, helped inform development our BA.4/BA.5-adapted vaccine.

Язык: Английский

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