Post-pandemic memory T cell response to SARS-CoV-2 is durable, broadly targeted, and cross-reactive to the hypermutated BA.2.86 variant

Cell Host & Microbe, Journal Year: 2024, Volume and Issue: 32(2), P. 162 - 169.e3

Published: Jan. 10, 2024

Ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolution has given rise to recombinant Omicron lineages that dominate globally (XBB.1), as well the emergence of hypermutated variants (BA.2.86). In this context, durable and cross-reactive T cell immune memory is critical for continued protection against COVID-19. We examined responses SARS-CoV-2 approximately 1.5 years since first emerged. describe sustained CD4+ CD8+ spike-specific in healthcare workers South Africa (n = 39) who were vaccinated experienced at least one infection. Spike-specific cells are highly with all tested, including BA.2.86. Abundant nucleocapsid membrane-specific detectable most participants. The bulk SARS-CoV-2-specific have an early-differentiated phenotype, explaining their persistent nature. Overall, hybrid immunity leads accumulation spike non-spike evident 3.5 after start pandemic, preserved recognition mutated variants.

Language: Английский

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Genome‐based comparison between the recombinant SARS‐CoV‐2 XBB and its parental lineages

Journal of Medical Virology, Journal Year: 2023, Volume and Issue: 95(3)

Published: Feb. 28, 2023

Abstract Recombination is the main contributor to RNA virus evolution, and SARS‐CoV‐2 during pandemic produced several recombinants. The most recent recombinant lineage labeled XBB, also known as Gryphon, which arose from BJ.1 BM.1.1.1. Here we performed a genome‐based survey aimed compare new with its parental lineages that never became dominant. Genetic analyses indicated XBB first descendant XBB.1 show an evolutionary condition typical of blind background no further epidemiologically relevant descendant. variability expansion capabilities are slightly higher than lineages. Bayesian Skyline Plot indicates reached plateau around October 6, 2022 after initial rapid growth viral population size did not expand, November 10, levels genetic decreased. Simultaneously reduction size, increase sub‐lineage occurred, in turn 9, showing kind vicariance direct progenitors. Structure analysis affinity for ACE2 surface XBB/XBB.1 RBDs weaker BA.2 RBD. In conclusion, at present do evidence about particular danger or high capability. Genome‐based monitoring must continue uninterrupted individuate if mutations can make more dangerous generate subvariants different

Language: Английский

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Neutralizing antibody and CD8+ T cell responses following BA.4/5 bivalent COVID-19 booster vaccination in adults with and without prior exposure to SARS-CoV-2

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

Published: March 20, 2024

As severe acute respiratory coronavirus 2 (SARS-CoV-2) variants continue to emerge, it is important characterize immune responses against which can inform on protection efficacies following booster vaccination. In this study, neutralizing breadth and antigen-specific CD8 + T cell were analyzed in both infection-naïve infection-experienced individuals administration of a bivalent Wuhan-Hu-1+BA.4/5 Comirnaty ® mRNA vaccine. Significantly higher titers found after vaccination compared the pre-third time point. Further, omicron variants, including BA.1, BA.2, BA.5, BQ.1 XBB.1, was be boosted SARS-CoV-2-specific cells identified, but with no evidence that frequencies increased vaccinations. Spike protein-specific only detected non-spike-specific infection. Both spike-specific at much lower than specific cytomegalovirus (CMV), Epstein-Barr virus (EBV) influenza (Flu). Taken together, these results show vaccine neutralization newer SARS-CoV-2 able induce spike responses, are maintained longitudinally.

Language: Английский

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Molecular In-Depth on the Epidemiological Expansion of SARS-CoV-2 XBB.1.5

Microorganisms, Journal Year: 2023, Volume and Issue: 11(4), P. 912 - 912

Published: March 31, 2023

Since the beginning of pandemic, generation new variants periodically recurs. The XBB.1.5 SARS-CoV-2 variant is one most recent. This research was aimed at verifying potential hazard this subvariant. To achieve objective, we performed a genome-based integrative approach, integrating results from genetic variability/phylodynamics with structural and immunoinformatic analyses to obtain as comprehensive viewpoint possible. Bayesian Skyline Plot (BSP) shows that viral population size reached plateau phase on 24 November 2022, number lineages peaked same time. evolutionary rate relatively low, amounting 6.9 × 10-4 subs/sites/years. NTD domain identical for XBB.1 whereas their RBDs only differ mutations position 486, where Phe (in original Wuhan) replaced by Ser in XBB XBB.1, Pro XBB.1.5. seems spread more slowly than sub-variants have caused concerns 2022. multidisciplinary molecular in-depth here does not provide evidence particularly high risk expansion. Results indicate possess features become new, global, public health threat. As now, its current make-up, represent dangerous variant.

Language: Английский

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mRNA-1273 vaccinated inflammatory bowel disease patients receiving TNF inhibitors develop broad and robust SARS-CoV-2-specific CD8+ T cell responses

Journal of Autoimmunity, Journal Year: 2024, Volume and Issue: 144, P. 103175 - 103175

Published: Feb. 21, 2024

SARS-CoV-2-specific CD8

Language: Английский

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Long-term humoral and cellular immunity against vaccine strains and Omicron subvariants (BQ.1.1, BN.1, XBB.1, and EG.5) after bivalent COVID-19 vaccination

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

Published: May 2, 2024

Background The assessment of long-term humoral and cellular immunity post-vaccination is crucial for establishing an optimal vaccination strategy. Methods This prospective cohort study evaluated adults (≥18 years) who received a BA.4/5 bivalent vaccine. We measured the anti-receptor binding domain immunoglobulin G antibody neutralizing antibodies (NAb) against wild-type Omicron subvariants (BA.5, BQ.1.1, BN.1, XBB.1 EG.5) up to 9 months post-vaccination. T-cell immune responses were before 4 weeks after vaccination. Results A total 108 (28 SARS-CoV-2-naïve 80 previously infected) participants enrolled. Anti-receptor (U/mL) levels higher at than baseline in SAR-CoV-2-naïve individuals (8,339 vs. 1,834, p<0.001). NAb titers significantly both groups, whereas EG.5 was negligible all time points. response (median spot forming unit/10 6 cells) highly cross-reactive (wild-type/BA.5/XBB.1.5, 38.3/52.5/45.0 individuals; 51.6/54.9/54.9 SARS-CoV-2-infected individuals) post-vaccination, with insignificant boosting Conclusion Remarkable neutralization observed vaccination, but not EG.5. cross-reactive.

Language: Английский

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Immunity against conserved and non-conserved Spike epitopes after COVID-19 booster vaccination provides long-term protection against symptomatic Omicron infections

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 8, 2025

The objective of this study was to investigate the features immune protection against SARS-CoV-2 infection in a single cohort during 6–17 months following booster immunization with an mRNA-based vaccine. results illustrate influence humoral and cellular immunity on efficacy Notably, neutralizing antibody titers were found serve as reasonably reliable correlate prior immunization. However, predictive power largely lost after boosting. loss appears be due critical remodeling response Our findings support hypothesis that both conserved non-conserved epitopes viral Spike protein's receptor-binding domain (RBD) is crucial for optimal long-term Omicron infection. While may provide cross-variant protection, antibodies targeting RBD play pivotal role achieving maximum protection. These observations highlight repeated shaping landscape reinforce necessity considering components, alongside intended use considerations, when assessing vaccine developing future strategies.

Language: Английский

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Myeloid‐Driven Immune Suppression Subverts Neutralizing Antibodies and T Cell Immunity in Severe COVID‐19

Journal of Medical Virology, Journal Year: 2025, Volume and Issue: 97(4)

Published: April 1, 2025

The objective of this study was to better understand immune failure mechanisms during severe acute respiratory syndrome coronavirus 2, SARS-CoV-2 infection, which are critical for developing targeted vaccines and effective treatments. We collected 34 cases representing different disease severities performed high-quality single-cell TCR/BCR sequencing analyze the peripheral cell profiles. Additionally, we assessed antibody-neutralizing activity through in vitro experiments. Our integrated multiomics analysis uncovers a profound paradox COVID-19: hyperinflammation coexists with immunosuppression, driven by distinct yet interconnected dysregulatory mechanisms. Severe patients develop robust humoral immunity, evidenced clonally expanded plasma cells producing neutralizing antibodies (e.g., IGHG1-dominated responses) antigen-specific T activation. However, these protective responses counteracted myeloid-driven particularly CD14+ HMGB2+ monocytes exhibiting metabolic reprogramming HLA-DR downregulation, coupled progressive exhaustion characterized IFN-γ/TNF-α hyperactivation impaired antigen presentation. Importantly, prolonged viral persistence arises from coordinate cellular immunity-antibody-mediated neutralization cannot compensate defective cytotoxic function monocyte-mediated suppression. These findings highlight necessity therapeutic strategies that simultaneously enhance antibody effector functions Fc optimization), restore exhausted cells, reverse myeloid They also importance designed elicit balanced B memory durable responses, preventing progression. By addressing dual challenges such approaches could coordination improve outcomes COVID-19.

Language: Английский

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Impact of Mutations in Immunodominant Regions of SARS-CoV-2 Variants on Recognition by CD8+ T Cell: An In Silico Analysis

Journal of Infection and Public Health, Journal Year: 2025, Volume and Issue: unknown, P. 102803 - 102803

Published: May 1, 2025

Language: Английский

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Distinct CD8+ T-cell types Associated with COVID-19 Severity in Unvaccinated HLA-A2+ Patients

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 14, 2025

Abstract Although emerging data have revealed the critical role of memory CD8 + T cells in preventing and controlling SARS-CoV-2 infection, virus-specific T-cell responses against its innate-like subsets unvaccinated COVID-19 patients with various disease manifestations an HLA-restricted fashion remain to be understood. Here, we show strong association protective cellular immunity mild unique cell types virus HLA-A2 restricted manner. ELISpot assays reveal that SARS-CoV-2-specific are significantly higher than severe patients, whereas neutralizing antibody correlate severity. Single-cell analyses HLA-A2-restricted cells, which recognize highly conserved immunodominant epitopes, demonstrate divergent profiles versus disease. including cytotoxic KLRB1 CD8αα signatures, IFNG hi ID3 IL7R proliferative stem cell-like preferentially observed COVID-19, distinct terminally-differentiated predominantly detected COVID-19: activated FASL early-terminated or dysfunctional IL4R GATA3 subset. In conclusion, our findings suggest contrasting may dictate Figure Graphical abstract. epitope-specific subtypes associated patients. Potent gene signature (upper) (lower).

Language: Английский

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