Harnessing T-Cells for Enhanced Vaccine Development against Viral Infections

Vaccines, Journal Year: 2024, Volume and Issue: 12(5), P. 478 - 478

Published: April 29, 2024

Despite significant strides in vaccine research and the availability of vaccines for many infectious diseases, threat posed by both known emerging diseases persists. Moreover, breakthrough infections following vaccination remain a concern. Therefore, development novel is imperative. These must exhibit robust protective efficacy, broad-spectrum coverage, long-lasting immunity. One promising avenue lies leveraging T-cells, which play crucial role adaptive immunity regulate immune responses during viral infections. T-cell recognition can target highly variable or conserved proteins, memory T-cells offer potential durable Consequently, T-cell-based hold promise advancing efforts. This review delves into latest advancements across various platforms discusses associated challenges.

Language: Английский

---

PAD4 inhibition impacts immune responses in SARS-CoV-2 infection

Mucosal Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

---

Dissecting the COVID‐19 Immune Response: Unraveling the Pathways of Innate Sensing and Response to SARS‐CoV‐2 Structural Proteins

Journal of Molecular Recognition, Journal Year: 2025, Volume and Issue: 38(2)

Published: Feb. 5, 2025

ABSTRACT Severe acute respiratory syndrome coronavirus (SARS‐CoV), the virus responsible for COVID‐19, interacts with host immune system through complex mechanisms that significantly influence disease outcomes, affecting both innate and adaptive immunity. These interactions are crucial in determining disease's severity host's ability to clear virus. Given virus's substantial socioeconomic impact, high morbidity mortality rates, public health importance, understanding these is essential. This article examines diverse responses triggered by SARS‐CoV‐2's structural proteins, including spike (S), membrane (M), envelope (E), nucleocapsid (N) along nonstructural proteins (NSPs) open reading frames. play pivotal roles modulation, facilitating viral replication, evading detection, contributing severe inflammatory such as cytokine storms distress (ARDS). The employs strategies like suppressing type I interferon production disrupting key antiviral pathways, MAVS, OAS‐RNase‐L, PKR. study also explores pathways govern activation suppression of throughout COVID‐19. By analyzing sensing receptors initiated upon recognizing SARS‐CoV‐2 this review elucidates associated response Understanding offers valuable insights therapeutic interventions informs strategies, a deeper COVID‐19 immunopathogenesis.

Language: Английский

---

The comprehensive insights into the B-cells-mediated immune response against COVID-19 infection amid the ongoing evolution of SARS-CoV-2

Biomedicine & Pharmacotherapy, Journal Year: 2025, Volume and Issue: 185, P. 117936 - 117936

Published: March 8, 2025

Language: Английский

---

Deletion of a KSF Motif Attenuates NSP1 Host Cell Translation Shutoff and Impairs SARS-CoV-2 Virulence

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

Published: April 17, 2025

ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of disease 2019 (COVID-19), triggered a global pandemic with profound social and economic consequences. The viral spike (S) protein has been identified as key determinant SARS-CoV-2 pathogenicity. In this study, we demonstrate that Omicron BA.4 BA.5 variants, which have closely related S proteins, exhibit different virulence in K18-hACE2 transgenic mice. A comparison genomic sequences revealed differences between variants BA.5, including three amino acid deletion (ΔKSF) linker region non-structural 1 (NSP1) BA.4. Using reverse genetic systems, engineered recombinant (r)SARS-CoV-2 expressing NSP1, was significantly attenuated vivo , similar to natural isolate, compared rBA.5 wild-type (WT). This finding indicates NSP1 is responsible, at least part, for BA.5. Mechanistically, showed reduced ability inhibit host gene translation NSP1. Notably, rSARS-CoV-2 WA1 original strain containing same ΔKSF also rWA1 WT. Together, these findings highlight contributions inhibiting expression pathogenicity, well feasibility targeting rational design live-attenuated vaccines and/or antivirals. IMPORTANCE Understanding why some cause more severe than others crucial proper management or prophylactic therapeutic treatments. While most studies focus on protein, found another plays role severity among variants. small present variant, weakens virus shut down host’s immune response, making less When introduced into SARS- CoV-2 strain, became harmful. discovery suggests an important factor supports development new treatments against SARS-CoV-2. By uncovering NSP1’s pathogenesis, our study provides insights could help designing better strategies combat future

Language: Английский

---

Implications of SARS‐CoV‐2 Immunity in the Context of the Pathogenesis of COVID‐19, Immune Evasion of the Virus, and the Effectiveness of Vaccination

Published: May 28, 2024

Since severe acute respiratory syndrome coronavirus (SARS-CoV)-2 emerged in December 2019, significant research has been conducted around the world to understand virus- and vaccine-generated immune response, identify drivers of disease 19 (COVID-19). Although viral tropism is largely limited tract, SARS-CoV-2 infection can lead COVID-19 disease, which characterized by multiorgan failure permanent cognitive disorders. The combined effects virus-mediated inhibition host antiviral mechanisms recognition pathogen-associated molecules pattern receptors (PRRs) are main pathogenesis disease. innate system constitutes first line defense against limiting entry virus into cell, suppressing replication, detecting virus-infected cells, accelerating formation adaptive response. composed two basic B T serve different but complementary functions infections. critical role immunity clearing well known, its function development virus-induced immunopathogenesis remains poorly understood. characteristic humoral response creation specific antibodies each foreign antigen encountered. Antibodies that sense pathogens classified as neutralizing (nAbs) non-neutralizing (non-nAbs) based on their capacity neutralize inhibit membrane fusion. While nAbs exert activities blocking ACE2-dependent cells pathogens, non-nAbs often undetectable. level anti-SARS-CoV-2 serum mucosal tissues varies with stage severity infection. current vaccines elicit robust antibody responses, this effect decreases over time, due weakening emergence novel variants evade such Delta Omicron. may surveillance minimizing interfering cellular signaling. In review article, central responses effectiveness vaccines, evasion strategies discussed detail light knowledge.

Language: Английский

---

Using models to identify the causes of pre-symptomatic transmission from human infection data

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

Published: May 16, 2024

Abstract When disease transmission can precede symptom onset, containing outbreaks requires distinct strategies, like active surveillance. Yet it is rarely clear in advance when such interventions are needed, especially for emerging pathogens. Predicting pre-symptomatic would be easier with knowledge of the within-host dynamics that enable transmission. To investigate those dynamics, we survey controlled human infection (CHI) trials viral agents, which contain data on incubation times, duration, and potential following inoculation a known dose. We find all studies report information duration shedding, but few timing symptoms. Only one study provided shedding symptoms individual participants, norovirus inoculation. apply statistical model to time series show significantly greater faster replication, no evidence tradeoff between rate during phase. then compare models pathogen immune clearance, onset identify plausible assumptions about causes recover pattern peak if assume triggered by responses rather than abundance. relaxing standard assumption exponential growth replication enables Thus, CHI trials, paired models, illuminate underpinning transmission, guiding efforts improve control strategies. Significance statement The COVID-19 pandemic was exacerbated before remain unclear, hindering predict spread tailor novel For pathogens, varies across individuals, patterns may emerge from trials. surveyed finding only reported participants. fit simple data, correlates used more detailed e.g., trigger applying trial gives insight into drivers

Language: Английский

---

Differential action modes of Neutrophil Extracellular Trap-targeted drugs define T cell responses in SARS-CoV-2 infection.

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

Published: July 1, 2024

Abstract Neutrophil extracellular traps (NETs) play a dual role in SARS-CoV-2 infection, aiding early immune defense but also contributing to lung damage. While NET targeting may improve clinical outcomes its impact on adaptive immunity, crucial for fighting the virus, remains unclear. Our study demonstrates that both recombinant human DNase (rhDNase), degrading structure, and GSK484, inhibiting formation, reduce concentration infected mice, yet they differ their influence T cell responses. We show rhDNase does not responses, whereas GSK484 diminishes virus-specific In vitro , decreases dendritic antigen presentation by impairing uptake reduces IL-2 signaling affecting production cells. model of inflammation, antigen-specific activation proliferation, while shows potential boost responses via presence fragments threshold. findings suggest with or holds therapeutic treating distinct modes action shape during infection.

Language: Английский

---

Cxcl10 is required for survival during SARS-CoV-2 infection in mice

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

Published: Oct. 1, 2024

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of disease 2019 (COVID-19) pandemic, remains endemic worldwide ∼5 years since first documented case. COVID-19 is widely considered to be caused by a dysregulated immune response SARS-CoV-2 within tract. Circulating levels chemokine CXCL10 are strongly positively associated with poor outcome; however, its precise role in pathogenesis and suitability as therapeutic target have remained undefined. Here, we challenged 4-6 month old C57BL/6 mice genetically deficient

Language: Английский

---

Spectrum of COVID-19 induced liver injury: A review report

World Journal of Hepatology, Journal Year: 2024, Volume and Issue: 16(4), P. 517 - 536

Published: April 24, 2024

The coronavirus disease 2019 (COVID-19) pandemic has caused changes in the global health system, causing significant setbacks healthcare systems worldwide. This also shown resilience, flexibility, and creativity reacting to tragedy. severe acute respiratory syndrome 2 (SARS-CoV-2) infection targets most of tract, resulting a sickness called distress that may be fatal some individuals. Although lung is primary organ targeted by COVID-19 viruses, clinical aspect varied ranges from asymptomatic failure. However, due an unorganized immune response several affected mechanisms, liver experience cell injury, ischemic dysfunction, drug-induced which can result failure because system’s disordered other compromised processes end multisystem Patients with cirrhosis or those who have impaired more likely than groups worse results SARS-CoV-2 infection. We thus intend examine pathogenesis, current therapy, consequences damage concerning COVID-19.

Language: Английский

---