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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Vaccination impairs de novo immune response to omicron breakthrough infection, a precondition for the original antigenic sin

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

Опубликована: Апрель 10, 2024

Several studies have suggested the imprinting of SARS-CoV-2 immunity by original immune challenge without addressing formation de novo response to successive antigen exposures. As this is crucial for development antigenic sin, we assessed against mutated epitopes omicron after vaccine breakthrough. Our data demonstrate a robust humoral in thrice-vaccinated individuals following breakthrough which recall vaccine-induced memory. The and memory B cell responses altered regions surface proteins are impaired. T spike protein present due high cross-reactivity cells rather than response. findings, therefore, underpin speculation that vaccination may lead sin if future variants overcome immunity.

Язык: Английский

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Potential immune evasion of the severe acute respiratory syndrome coronavirus 2 Omicron variants

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Фев. 23, 2024

Coronavirus disease 2019 (COVID-19), which is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has a global pandemic. The Omicron variant (B.1.1.529) was first discovered in November 2021 specimens collected from Botswana, South Africa. become dominant worldwide, and several sublineages or subvariants have been identified recently. Compared to those of other mutants, most highly expressed amino acid mutations, with almost 60 mutations throughout genome, are spike (S) protein, especially receptor-binding domain (RBD). These increase binding affinity variants for ACE2 receptor, may also lead immune escape. Despite causing milder symptoms, epidemiological evidence suggests that exceptionally higher transmissibility, rates reinfection greater spread than prototype strain as well preceding variants. Additionally, overwhelming amounts data suggest levels specific neutralization antibodies against decrease vaccinated populations, although CD4 + CD8 T-cell responses maintained. Therefore, mechanisms underlying evasion still unclear. In this review, we surveyed current epidemic status potential escape Especially, focused on roles viral epitope antigenic drift, hybrid immunity, “original sin” mediating evasion. insights might supply more valuable concise information us understand spreading

Язык: Английский

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Additive effects of booster mRNA vaccination and SARS-CoV-2 Omicron infection on T cell immunity across immunocompromised states

Science Translational Medicine, Год журнала: 2023, Номер 15(704)

Опубликована: Июль 12, 2023

Suboptimal immunity to SARS-CoV-2 mRNA vaccination has frequently been observed in individuals with various immunodeficiencies. Given the increased antibody evasion properties of emerging subvariants, it is necessary assess whether other components adaptive generate resilient and protective responses against infection. We assessed T cell 279 individuals, covering five different immunodeficiencies healthy controls, before after booster vaccination, as well Omicron infection a subset patients. robust persistent Omicron-reactive that markedly upon correlated directly titers across all patient groups. Poor responsiveness immunocompromised or elderly was effectively counteracted by administration additional vaccine doses. Functionally, exhibited pronounced cytotoxic profile signs longevity, characterized CD45RA + effector memory subpopulations stem cell–like proliferative capacity. Regardless underlying immunodeficiency, booster-vaccinated Omicron-infected appeared protected severe disease enhanced diversified conserved Omicron-specific epitopes. Our findings indicate cells retain ability highly functional newly variants, even repeated antigen exposure immunological imprint from ancestral vaccination.

Язык: Английский

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A computationally designed antigen eliciting broad humoral responses against SARS-CoV-2 and related sarbecoviruses

Nature Biomedical Engineering, Год журнала: 2023, Номер unknown

Опубликована: Сен. 25, 2023

The threat of spillovers coronaviruses associated with the severe acute respiratory syndrome (SARS) from animals to humans necessitates vaccines that offer broader protection sarbecoviruses. By leveraging a viral-genome-informed computational method for selecting immune-optimized and structurally engineered antigens, here we show single antigen based on receptor binding domain spike protein sarbecoviruses elicits broad humoral responses against SARS-CoV-1, SARS-CoV-2, WIV16 RaTG13 in mice, rabbits guinea pigs. When administered as DNA immunogen or by vector modified vaccinia virus Ankara, optimized induced vaccine Delta variant SARS-CoV-2 mice genetically express angiotensin-converting enzyme 2 primed viral-vector (AZD1222) SARS-CoV-2. A formulation incorporating mRNA coding further validated its immunogenicity. Vaccines elicit immune across subgroups may counteract zoonotic betacoronaviruses.

Язык: Английский

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SARS-CoV-2 Omicron: Viral Evolution, Immune Evasion, and Alternative Durable Therapeutic Strategies

Viruses, Год журнала: 2024, Номер 16(5), С. 697 - 697

Опубликована: Апрель 28, 2024

Since the SARS-CoV-2 Omicron virus has gained dominance worldwide, its continual evolution with unpredictable mutations and patterns revoked all authorized immunotherapeutics. Rapid viral also necessitated several rounds of vaccine updates in order to provide adequate immune protection. It remains imperative understand how evolves into different subvariants causes escape as this could help reevaluate current intervention strategies mostly implemented clinics emergency measures counter pandemic and, importantly, develop new solutions. Here, we a review focusing on major events evolution, including features spike mutation that lead evasion against monoclonal antibody (mAb) therapy vaccination, suggest alternative durable options such ACE2-based experimental therapies superior mAbs address unprecedented virus. In addition, type unique virus-trapping molecules can zoonotic SARS coronaviruses, either from unknown animal hosts or established wild-life reservoirs SARS-CoV-2, even seasonal alpha coronavirus NL63 depends human ACE2 for infection.

Язык: Английский

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Long-term adaptive response in COVID-19 vaccine recipients and the effect of a booster dose

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Фев. 28, 2023

We examined the immune response in subjects previously infected with SARS-CoV2 and infection-naïve 9 months after primary 2-dose COVID-19 mRNA vaccination 3 booster dose a longitudinal cohort of healthcare workers. Nine vaccination, exhibited higher residual antibody levels, significant neutralizing activity against distinct variants compared to subjects. The humoral was associated levels receptor binding domain (RBD)-specific IgG+ IgA+ memory B cells. increased neither activity, nor T cell frequencies. Conversely, needed achieve comparable antibodies as those found vaccination. titer correlated anti-RBD IFNγ producing cells, face sustained response. Notably, pre-pandemic samples showed high Omicron cross-reactivity. These data show importance reinforcing immunological increasing circulating

Язык: Английский

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BA.1, BA.2 and BA.2.75 variants show comparable replication kinetics, reduced impact on epithelial barrier and elicit cross-neutralizing antibodies

PLoS Pathogens, Год журнала: 2023, Номер 19(2), С. e1011196 - e1011196

Опубликована: Фев. 24, 2023

The Omicron variant of SARS-CoV-2 is capable infecting unvaccinated, vaccinated and previously-infected individuals due to its ability evade neutralization by antibodies. With multiple sub-lineages emerging in the last 12 months, there inadequate information on quantitative antibody response generated upon natural infection with whether these antibodies offer cross-protection against other variant. In this study, we characterized growth kinetics Kappa, Delta variants Calu-3 cells. Relatively higher amounts infectious virus titers, cytopathic effect disruption epithelial barrier functions was observed whereas led a more robust induction interferon pathway, lower level replication mild barrier. BA.1, BA.2 BA.2.75 were comparable cell culture subset significant increase binding neutralizing all three but lowest Finally, show that Cu 2+ , Zn Fe salts inhibited vitro RdRp activity only both culture. Thus, our results suggest high levels interferons induced may counter spread. Waning titers rendered subjects susceptible elicits can cross-react concern.

Язык: Английский

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SARS-CoV-2 Omicron infection augments the magnitude and durability of systemic and mucosal immunity in triple-dose CoronaVac recipients

mBio, Год журнала: 2024, Номер 15(4)

Опубликована: Март 8, 2024

The inactivated whole-virion vaccine, CoronaVac, is one of the most widely used coronavirus disease 2019 (COVID-19) vaccines worldwide. There a paucity data indicating durability immune response and impact imprinting induced by CoronaVac upon Omicron infection. In this prospective cohort study, 41 recipients triple-dose 14 unvaccinated individuals were recruited. We comprehensively profiled adaptive parameters in both groups, including spike-specific immunoglobulin (Ig) G IgA titers, neutralizing activity, B cells, circulating follicular helper T (cTfh) CD4+ CD8+ their memory subpopulations at 12 months after third booster dose 4 20 weeks BA.5 Twelve vaccination, antibodies cellular responses detectable vaccinated individuals. infection significantly augmented magnitude, cross-reactivity, serum neutralization activities, Fc-mediated phagocytosis, nasal responses, activated cTfh cells for ancestral strain subvariants, compared to Notably, increase BA.5-specific immunity breakthrough was consistently comparable or higher than that strain, suggesting no evidence imprinting. Immune landscape analyses showed have better synchronization multiple components heterologous Our provide detailed insight into protective role COVID-19 vaccine shaping humoral anti-severe acute respiratory syndrome 2 analyzed before This study registered with ClinicalTrials.gov as NCT05680896.

Язык: Английский

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A virus-like particle candidate vaccine based on CRISPR/Cas9 gene editing technology elicits broad-spectrum protection against SARS-CoV-2

Antiviral Research, Год журнала: 2024, Номер 225, С. 105854 - 105854

Опубликована: Март 5, 2024

Язык: Английский

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