The immunopathogenesis of SARS-CoV-2 infection: Overview of lessons learned in the first 5 years

The Journal of Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: April 3, 2025

Abstract This review provides a broad overview of lessons learned in the five years since COVID-19 was identified. It is bimodal disease, starting with an initially virus-driven phase, followed by resolution or ensuing inappropriate immune activation causing severe inflammation that no longer strictly virus dependent. Humoral immunity beneficial for preventing attenuating early stage, without benefit once later stage begins. Neutralizing antibodies elicited natural infection vaccination are short-lived and highly vulnerable to viral sequence variation. By contrast, cellular immunity, particularly CD8+ T cell arm, has role far less susceptible variation, longer-lived than antibodies. Finally, ill-defined phenomenon prolonged symptoms after acute infection, termed “long COVID,” poorly understood but may involve various immunologic defects hyperactivating immunosuppressive. Remaining issues include needing better understand dysregulation disease allow more tailored therapeutic interventions, developing antibody strategies cope spike variability, prolonging vaccine efficacy, unraveling mechanisms long COVID design approaches.

Language: Английский

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Electrochemical Aptasensor Based on Topological Material Bi₂Se₃ Sheets for Sensitive Detection of Interferon-γ

ACS Applied Bio Materials, Journal Year: 2025, Volume and Issue: unknown

Published: April 7, 2025

Interferon-gamma (IFN-γ), an essential inflammatory cytokine, is intricately associated with a variety of fatal diseases as key early biomarker. In this work, we designed and constructed electrochemical aptasensor based on topological insulator Bi2Se3 sheets. Micron-scale sheets were prepared by exfoliation from single crystals to make electrodes the aptasensors. The unique robust Dirac surface states could enhance charge transfer efficiency solid-liquid interface, improving performance developed exhibits linear response IFN-γ concentration in range 1-100 pg/mL detection limit low 0.6 pg/mL, enabling it meet clinical requirements. aptasensors also shows excellent stability selectivity. Furthermore, was applied human serum comparable standard enzyme-linked immunosorbent assay technique. Our work indicates that has great potential for application other possible biomarkers.

Language: Английский

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Five doses of the mRNA vaccination potentially suppress ancestral-strain stimulated SARS-CoV2-specific cellular immunity: a cohort study from the Fukushima vaccination community survey, Japan

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

Published: Aug. 16, 2023

The bivalent mRNA vaccine is recommended to address coronavirus disease variants, with additional doses suggested for high-risk groups. However, the effectiveness, optimal frequency, and number of remain uncertain. In this study, we examined long-term cellular humoral immune responses following fifth administration severe acute respiratory syndrome 2 (SARS-CoV-2) in patients undergoing hemodialysis. To our knowledge, first study monitor data on immunity dynamics populations after five vaccination, including vaccine. Whereas most maintained throughout observation period, observed reduced reactivity as measured by ancestral-strain-stimulated ELISpot assay a subset patients. Half individuals (50%; 14/28) three months dose, despite acquiring immunity. absence relationship between positive controls T-Spot suggests that these alterations were specific SARS-CoV-2. multivariable analysis, participants aged ≥70 years showed marginally significant lower likelihood having reactive results. Notably, among 14 who received heterologous vaccines, 13 successfully acquired immunity, supporting effectiveness strategy. These findings provide valuable insights future vaccination strategies vulnerable populations. further research needed evaluate involvement tolerance exhaustion through repeated optimize immunization strategies.

Language: Английский

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The molecular mechanisms of CD8+ T cell responses to SARS-CoV-2 infection mediated by TCR-pMHC interactions

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

Published: Oct. 10, 2024

Cytotoxic CD8

Language: Английский

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Predominantly defective CD8+ T cell immunity to SARS-CoV-2 mRNA vaccination in lung transplant recipients

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: June 8, 2023

Although mRNA vaccines have overall efficacy preventing morbidity/mortality from SARS-CoV-2 infection, immunocompromised persons remain at risk. Antibodies mostly prevent early symptomatic but cellular immunity, particularly the virus-specific CD8+ T cell response, is protective against disease. Defects in responses to vaccination not been well characterized hosts; with lung transplantation are vulnerable vaccine failure severe illness.Comparison groups included and no history of COVID-19 (21 19 after initial a third booster respectively), 8 participants recovered COVID-19, 22 non-immunocompromised healthy control individuals (without COVID-19). Anti-spike were assayed by stimulating peripheral blood mononuclear cells (PBMCs) pooled small overlapping peptides spanning spike protein, followed intracellular cytokine staining (ICS) flow cytometry for release cytokines response stimulation, including negative controls (no peptide stimulation) positive (phorbol myristate acetate [PMA] ionomycin stimulation). To evaluate low frequency memory responses, PBMCs cultured presence mRNA-1273 14 days before this evaluation.Ionophore stimulation revealed less inflammatory milieu terms interleukin (IL)-2, IL-4, IL-10 profiling individuals, reflecting effect immunosuppressive treatments. Similar what we previously reported vaccinees, spike-specific recipients undetectable (< 0.01%) when tested 2 weeks or later, detectable vitro culture enrich responses. This was also seen COVID-19-recovered recipients. Comparison their enriched relatively similar CD4+ memory, markedly reduced both primary dose. These correlated age time transplantation. The vaccine-induced group, poorly groups.These results reveal specific defect cells, which key roles transplanted organ rejection antiviral effector Overcoming will require strategies enhance immunogenicity persons.

Language: Английский

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A Phase I/II Randomized Trial of Higher Dose mRNA-1273 Boosters in Lung Transplant Recipients

OBM Transplantation, Journal Year: 2024, Volume and Issue: 08(04), P. 1 - 11

Published: Nov. 20, 2024

Higher-dose mRNA booster vaccines have not been well studied for transplant recipients. This study evaluated the safety, reactogenicity and immunogenicity of higher dose mRNA-1273 among lung recipients (LTRs). phase 1/2 open-label randomized clinical trial higher-dose vaccination enrolled nineteen adult LTRs into 50 ug (n=8) vs. 100 (n=11) groups before enrollment was terminated due to availability bivalent mRNA-1273.222 vaccine. Local systemic predominantly mild or moderate in severity both groups, mostly limited pain at injection site, fatigue headache. Humoral cellular immune responses were weak. Overall, 75% 64% had detectable neutralizing antibodies on Day 30 (vs. 63% 55% 1), respectively. On 30, 50% spike-specific CD4+ IFN 29% 36% CD8+ 45% 1) two that are attenuated compared with non-immunocompromised population. Administration doses solid organ patients may be warranted. Clinical NCT05280158.

Language: Английский

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