The impact of pre-existing cross-reactive immunity on SARS-CoV-2 infection and vaccine responses

Nature reviews. Immunology, Journal Year: 2022, Volume and Issue: 23(5), P. 304 - 316

Published: Dec. 20, 2022

Language: Английский

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SARS-CoV-2-specific immune responses and clinical outcomes after COVID-19 vaccination in patients with immune-suppressive disease

Nature Medicine, Journal Year: 2023, Volume and Issue: 29(7), P. 1760 - 1774

Published: July 1, 2023

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune responses and infection outcomes were evaluated in 2,686 patients with varying immune-suppressive disease states after administration of two Coronavirus Disease 2019 (COVID-19) vaccines. Overall, 255 2,204 (12%) failed to develop anti-spike antibodies, an additional 600 (27%) generating low levels (<380 AU ml −1 ). Vaccine failure rates highest ANCA-associated vasculitis on rituximab (21/29, 72%), hemodialysis immunosuppressive therapy (6/30, 20%) solid organ transplant recipients (20/81, 25% 141/458, 31%). SARS-CoV-2-specific T cell detected 513 580 (88%) patients, lower magnitude or proportion hemodialysis, allogeneic hematopoietic stem transplantation liver (versus healthy controls). Humoral against Omicron (BA.1) reduced, although cross-reactive sustained all participants for whom these data available. BNT162b2 was associated higher antibody but cellular compared ChAdOx1 nCoV-19 vaccination. We report 474 SARS-CoV-2 episodes, including 48 individuals hospitalization death from COVID-19. Decreased both the serological response severe we identified clinical phenotypes that may benefit targeted COVID-19 therapeutic strategies.

Language: Английский

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SARS-CoV-2 breakthrough infection induces rapid memory and de novo T cell responses

Immunity, Journal Year: 2023, Volume and Issue: 56(4), P. 879 - 892.e4

Published: March 22, 2023

Language: Английский

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Magnitude of venous or capillary blood-derived SARS-CoV-2-specific T cell response determines COVID-19 immunity

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Sept. 21, 2022

T cells specific for SARS-CoV-2 are thought to protect against infection and development of COVID-19, but direct evidence this is lacking. Here, we associated whole-blood-based measurement SARS-CoV-2-specific interferon-γ-positive cell responses with positive COVID-19 diagnostic (PCR and/or lateral flow) test results up 6 months post-blood sampling. Amongst 148 participants donating venous blood samples, response magnitude significantly greater in those who remain protected versus become infected (P < 0.0001); relatively low a 43.2% risk infection, whereas high reduces 5.4%. These findings recapitulated further 299 testing scalable capillary blood-based assay that could facilitate the acquisition population-scale immunity data (14.9% 4.4%, respectively). Hence, can prognosticate should be assessed when monitoring individual population status.

Language: Английский

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Evolution of long-term vaccine-induced and hybrid immunity in healthcare workers after different COVID-19 vaccine regimens

Med, Journal Year: 2023, Volume and Issue: 4(3), P. 191 - 215.e9

Published: Feb. 16, 2023

Both infection and vaccination, alone or in combination, generate antibody T cell responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the maintenance of such responses-and hence protection from disease-requires careful characterization. In a large prospective study UK healthcare workers (HCWs) (Protective Immunity Cells Healthcare Workers [PITCH], within larger SARS-CoV-2 Reinfection Evaluation [SIREN] study), we previously observed that prior strongly affected subsequent cellular humoral immunity induced after long short dosing intervals BNT162b2 (Pfizer/BioNTech) vaccination.

Language: Английский

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In search of a pan-coronavirus vaccine: next-generation vaccine design and immune mechanisms

Cellular and Molecular Immunology, Journal Year: 2023, Volume and Issue: 21(2), P. 103 - 118

Published: Dec. 26, 2023

Abstract Members of the coronaviridae family are endemic to human populations and have caused several epidemics pandemics in recent history. In this review, we will discuss feasibility progress toward ultimate goal creating a pan-coronavirus vaccine that can protect against infection disease by all members coronavirus family. We detail unmet clinical need associated with continued transmission SARS-CoV-2, MERS-CoV four seasonal coronaviruses (HCoV-OC43, NL63, HKU1 229E) humans potential for future zoonotic coronaviruses. highlight how first-generation SARS-CoV-2 vaccines natural history studies greatly increased our understanding effective antiviral immunity informed next-generation design. then consider ideal properties propose blueprint type may offer cross-protection. Finally, describe subset diverse technologies novel approaches being pursued developing broadly or universally protective

Language: Английский

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T cell immune memory after covid-19 and vaccination

BMJ Medicine, Journal Year: 2023, Volume and Issue: 2(1), P. e000468 - e000468

Published: Nov. 1, 2023

The T cell memory response is a crucial component of adaptive immunity responsible for limiting or preventing viral reinfection. after infection with the SARS-CoV-2 virus vaccination broad, and spans multiple proteins epitopes, about 20 in each individual. So far long lasting provides high level cross reactivity hence resistance to escape by variants virus, such as omicron variant. All current vaccine regimens tested produce robust responses, heterologous will probably enhance protective responses through increased breadth. could have major role protecting against severe covid-19 disease rapid clearance early presentation presence reactive cells might this protection. likely provide ongoing protection admission hospital death, development pan-coronovirus future proof new pandemic strains.

Language: 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, Journal Year: 2023, Volume and Issue: 15(704)

Published: July 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.

Language: Английский

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A quest for universal anti-SARS-CoV-2 T cell assay: systematic review, meta-analysis, and experimental validation

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

Published: Jan. 2, 2024

Abstract Measuring SARS-CoV-2-specific T cell responses is crucial to understanding an individual’s immunity COVID-19. However, high inter- and intra-assay variability make it difficult define cells as a correlate of protection against To address this, we performed systematic review meta-analysis 495 datasets from 94 original articles evaluating using three assays – Activation Induced Marker (AIM), Intracellular Cytokine Staining (ICS), Enzyme-Linked Immunospot (ELISPOT), defined each assay’s quantitative range. We validated these ranges samples 193 SARS-CoV-2-exposed individuals. Although IFNγ ELISPOT was the preferred assay, our experimental validation suggested that under-represented repertoire. Our data indicate combination AIM ICS or FluoroSpot assay would better represent frequency, polyfunctionality, compartmentalization antigen-specific responses. Taken together, results contribute defining propose choice can be employed understand cellular immune response viral diseases.

Language: Английский

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Combined anti-S1 and anti-S2 antibodies from hybrid immunity elicit potent cross-variant ADCC against SARS-CoV-2

JCI Insight, Journal Year: 2023, Volume and Issue: 8(15)

Published: June 20, 2023

Antibodies capable of neutralising SARS-CoV-2 are well studied, but Fc receptor-dependent antibody activities that can also significantly impact the course infection have not been studied in such depth. As most vaccines induce only anti-spike antibodies, here we investigated spike-specific antibody-dependent cellular cytotoxicity (ADCC). Vaccination produced antibodies weakly induced ADCC, however, from individuals who were infected prior to vaccination ('hybrid' immunity) elicited strong ADCC. Quantitative and qualitative aspects humoral immunity contributed this capability, with skewing IgG production towards S2, S1 hybrid evoking responses against both domains. targeting spike domains support NK cell activation, three regions reactivity outside receptor-binding domain (RBD) corresponding potent Consequently, ADCC by ancestral antigen was conserved variants containing neutralisation escape mutations RBD. Induction recognising a broad range epitopes eliciting durable may partially explain why provides superior protection disease than alone, demonstrates spike-only subunit would benefit strategies combined anti-S1 S2 responses.

Language: Английский

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