Intranasal recombinant protein subunit vaccine targeting TLR3 induces respiratory tract IgA and CD8 T cell responses and protects against respiratory virus infection

EBioMedicine, Journal Year: 2025, Volume and Issue: 113, P. 105615 - 105615

Published: Feb. 20, 2025

Language: Английский

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T cell receptor usage and epitope specificity amongst CD8+ and CD4+ SARS-CoV-2-specific T cells

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 28, 2025

Introduction The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome 2 (SARS-CoV-2), has highlighted the critical importance of understanding protective long-lasting immune responses. This study investigates epitope specificity, T cell receptor (TCR) usage, and phenotypic changes in SARS-CoV-2-specfic CD8 + CD4 cells over time convalescent individuals with COVID-19. Methods Peripheral blood mononuclear (PBMCs) were collected from 28 unvaccinated primary SARS-CoV-2 infection (6 identified as D614G variant, clade 20C) analyzed up to 12 months post-symptom onset. Antigen-specific using flow cytometry single-cell RNA sequencing (scRNAseq) specific dextramer antibody reagents. TCR clonotypes activation markers characterized explore dynamics. Results SARS-CoV-2-specific exhibited waning frequencies long-term, transitioning memory-like a naïve-like state. scRNAseq revealed specificity against both spike non-spike antigens increased CD95 CD127 expression time, indicating that may represent stem memory cells, which are multipotent self-renewing, likely important for long-lived immunity. clonal expansion was observed mainly overlapping beta chain (TRB)-complementary determining region 3 (CDR3) sequences between participants, suggesting shared public epitope-specific repertoires SARS-CoV-2. Further, unique spike-specific high identified, play crucial role long-term protection. Discussion highlights epitope-specificity heterogeneity, some immunodominant responses, suggests potential Shared offers insights into cross-reactive clones, providing valuable information optimizing vaccine strategies emerging variants. findings underscore cellular immunity protection emphasizes

Language: Английский

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SARS-CoV-2 Recombinants: Genomic Comparison between XBF and Its Parental Lineages

Microorganisms, Journal Year: 2023, Volume and Issue: 11(7), P. 1824 - 1824

Published: July 17, 2023

Recombination events are very common and represent one of the primary drivers RNA virus evolution. The XBF SARS-CoV-2 lineage is most recently generated recombinants during COVID-19 pandemic. It a recombinant BA.5.2.3 BA.2.75.3, both descendants lineages that caused many concerns (BA.5 BA.2.75, respectively). Here, we performed genomic survey focused on comparing with its parental to provide comprehensive assessment evolutionary potential, epidemiological trajectory, potential risks. Genetic analyses indicated although initially showed typical expansion depicted by steep curve, causing several concerns, currently there no indication significant or contagion rate surpassing other active previously prevalent lineages. BSP peak has been reached around 19 October 2022 then genetic variability suffered slight oscillations until early 5 March 2023 when population size reduced for last time starting plateau still lasting. Structural confirmed also indicating properties NTDs RBDs present difference. Of course, cautionary measures must be taken genome-based monitoring remains best tool detecting any important changes in viral genome composition.

Language: Английский

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Immunogenicity and efficacy of a novel multi-patch SARS-CoV-2/COVID-19 vaccine candidate

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: June 19, 2023

Introduction While there has been considerable progress in the development of vaccines against SARS-CoV-2, largely based on S (spike) protein virus, less made with delivering different viral antigens cross-reactive potential. Methods In an effort to develop immunogen capacity induce broad antigen presentation, we have designed a multi-patch synthetic candidate containing dominant and persistent B cell epitopes from conserved regions SARS-CoV-2 structural proteins associated long-term immunity, termed CoV2-BMEP. Here describe characterization, immunogenicity efficacy CoV2-BMEP using two delivery platforms: nucleic acid DNA attenuated modified vaccinia virus Ankara (MVA). Results cultured cells, both vectors produced main about 37 kDa as well heterogeneous size ranging between 25-37 kDa. C57BL/6 mice, homologous heterologous prime/boost combination induced activation SARS-CoV-2-specific CD4 CD8 T responses, more balanced + response detected lungs. The MVA/MVA immunization regimen elicited highest specific responses spleen detectable binding antibodies (bAbs) N SARS-CoV-2. susceptible k18-hACE2 Tg doses MVA-CoV2-BMEP S- N-specific bAbs cross-neutralizing variants concern (VoC). After challenge, all animals control unvaccinated group succumbed infection while vaccinated high titers neutralizing were fully protected mortality, correlating reduction lungs inhibition cytokine storm. Discussion These findings revealed novel infection, broader presentation mechanism than approved solely antigen.

Language: Английский

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Spike protein is a key target for stronger and more persistent T-cell responses—a study of mild and asymptomatic SARS-CoV-2 infection

International Journal of Infectious Diseases, Journal Year: 2023, Volume and Issue: 136, P. 49 - 56

Published: Sept. 6, 2023

Understanding the immune response in very mild and asymptomatic COVID-19 is crucial for developing effective vaccines immunotherapies, yet remains poorly characterized. This longitudinal study examined evolution of interferon (IFN)-γ responses to SARS-CoV-2 peptides 109 or mildly symptomatic Ugandan patients across 365 days explored their association with antibody generation.

Language: Английский

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Genomic surveillance and vaccine response to the dominant SARS-CoV-2 XBB lineage in Rio Grande do Sul

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: July 22, 2024

The COVID-19 pandemic has been marked by novel viral variants, posing challenges to global public health. Recombination, a evolution mechanism, is implicated in SARS-CoV-2's ongoing evolution. XBB recombinant lineage, known for evading antibody-mediated immunity, exhibits higher transmissibility without increased disease severity. We investigated the prevalence and genomic features of SARS-CoV-2-positive cases Rio Grande do Sul (RS), Brazil. sequenced 357 samples from epidemiological weeks (EW) 47/2022 17/2023, included 389 publicly available sequences. Clinical data were obtained DATASUS, e-SUS, SIVEP GRIPE (data recording systems Brazilian Ministry Health). Of these, 143 classified as 586 other Omicron lineages. In March 2023 (EW 10), became dominant, accounting 83.3% cases. 97.7% XBB-infected patients successfully recovered infection, with low mortality rate (2.3%). Even after receiving three vaccine doses having previously infected, 59.5% experienced reinfection XBB. However, 54% individuals, interval between their infection last dose exceeded one year, potentially leading decline antibody levels. addition, we identified 90 mutations RS circulating XBB, spread throughout genome, notably Spike protein region associated immune resistance. This study provides insights into dynamics impact variant becoming predominant first time state. Continued surveillance SARS-CoV-2 crucial effective health management.

Language: Английский

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T cell epitope mapping reveals immunodominance of evolutionarily conserved regions within SARS-CoV-2 proteome.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 24, 2024

As SARS-CoV-2 variants continue to emerge capable of evading neutralizing antibodies, it has become increasingly important fully understand the breadth and functional profile T cell responses determine their impact on immune surveillance variant strains. Here, sampling healthy individuals, we profiled kinetics polyfunctionality immunity elicited by mRNA vaccination. Modeling anti-spike against ancestral strains suggested that epitope immunodominance cross-reactivity are major predictive determinants immunity. To identify immunodominant epitopes across viral proteome, generated a comprehensive map CD4+ CD8+ within non-spike proteins induced polyfunctional in convalescent patients. We found mainly resided regions were minimally disrupted mutations emerging variants. Conservation analysis historical human coronaviruses combined with silico alanine scanning mutagenesis underscored importance mutationally-constrained regions. Collectively, these findings potentially providing variants, inform design next-generation vaccines targeting antigens throughout proteome for broader more durable protection.

Language: Английский

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SARS-CoV-2-specific T cell responses: a comparative analysis between QuantiFERON SARS-CoV-2, T-SPOT.COVID, and an in-house Omicron ELISpot

Journal of Virological Methods, Journal Year: 2024, Volume and Issue: 327, P. 114949 - 114949

Published: May 6, 2024

T cell immunity plays a pivotal role in mitigating the severity of coronavirus disease 2019 (COVID-19). Therefore, reliable functional assays are required to evaluate severe acute respiratory syndrome 2 (SARS-CoV-2)-specific specific patient populations. We recruited cohort 23 healthcare workers who received their bivalent Omicron BA.1 / ancestral mRNA booster vaccination or were infected with variant at median 144 days and 227 before blood collection, respectively. In this cohort, we compared performances two widely utilized commercial SARS-CoV-2 interferon-gamma release (IGRAs), i.e., QuantiFERON T-SPOT.COVID, an in-house designed enzyme-linked immunospot (ELISpot). The T-SPOT.COVID detected spike-specific cells 34.8% 21.7% participants, Moreover, our ELISpot that included BA.4 BA.5 full-spike peptides responses 47.8% participants was strongly associated T-SPOT.COVID. evaluation using commercially accessible may yield disparate outcomes as results from different not directly comparable. A should be considered assess Omicron-specific immunity.

Language: Английский

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Newcastle disease virus vector-based SARS-CoV-2 vaccine candidate AVX/COVID-12 activates T cells and is recognized by antibodies from COVID-19 patients and vaccinated individuals

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: May 30, 2024

Introduction Several effective vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed and implemented in the population. However, current production capacity falls short of meeting global demand. Therefore, it is crucial to further develop novel vaccine platforms that can bridge distribution gap. AVX/COVID-12 a vector-based utilizes Newcastle Disease virus (NDV) present SARS-CoV-2 spike protein immune system. Methods This study aims analyze antigenicity candidate by examining antibody binding T-cell activation individuals infected with or variants concern (VOCs), as well healthy volunteers who received disease 2019 (COVID-19) vaccinations. Results Our findings indicate effectively binds antibodies activates T-cells 3 doses BNT162b2 AZ/ChAdOx-1-S vaccines. Furthermore, stimulation from patients recipients resulted their proliferation secretion interferon-gamma (IFN-γ) both CD4+ CD8+ T-cells. Discussion The vectored demonstrates ability stimulate robust cellular responses recognized primed viruses patients, mRNA These results support inclusion booster vaccination programs aimed at addressing COVID-19 caused its VOCs.

Language: Английский

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Breakthrough SARS-COV-2 infection induces broad anti-viral T cell immunity

iScience, Journal Year: 2023, Volume and Issue: 26(12), P. 108474 - 108474

Published: Nov. 15, 2023

Vaccines have curtailed the devastation wrought by COVID-19. Nevertheless, emerging variants result in a high incidence of breakthrough infections. Here we assess impact vaccination and infection on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) T cell immunity. We demonstrate that COVID-19 induces robust spike-specific responses that, within CD4+ compartment, display comparable IFN-γ to SARS-CoV-2 without vaccination. Vaccine-induced CD8+ however, were significantly greater than those primed alone. This increased responsiveness is associated with induction novel HLA-restricted epitopes not alone (without vaccination). Despite these augmented responses, still induced de novo against additional HLA-associated immunodominance hierarchies consistent unvaccinated convalescent individuals. study demonstrates unique modulation anti-viral multiple viral antigens following consecutive yet distinct priming events infection.

Language: Английский

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