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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High frequencies of alpha common cold coronavirus/SARS-CoV-2 cross-reactive functional CD4+ and CD8+ memory T cells are associated with protection from symptomatic and fatal SARS-CoV-2 infections in unvaccinated COVID-19 patients

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

Published: March 28, 2024

Background Cross-reactive SARS-CoV-2-specific memory CD4 + and CD8 T cells are present in up to 50% of unexposed, pre-pandemic, healthy individuals (UPPHIs). However, the characteristics cross-reactive associated with subsequent protection asymptomatic coronavirus disease 2019 (COVID-19) patients (i.e., unvaccinated who never develop any COVID-19 symptoms despite being infected SARS-CoV-2) remains be fully elucidated. Methods This study compares antigen specificity, frequency, phenotype, function between common cold coronaviruses (CCCs) SARS-CoV-2. T-cell responses against genome-wide conserved epitopes were studied early course a cohort 147 divided into six groups based on severity their symptoms. Results Compared severely ill fatal outcomes, displayed significantly: (i) higher rates co-infection 229E alpha species CCCs (α-CCC-229E); (ii) frequencies functional CD134 CD137 that cross-recognized from α-CCCs SARS-CoV-2 structural, non-structural, accessory proteins; (iii) lower CCCs/SARS-CoV-2 exhausted PD-1 TIM3 TIGIT CTLA4 cells, detected both ex vivo vitro . Conclusions These findings support crucial role functional, poly-antigenic α-CCCs/SARS-CoV-2 induced following previous seasonal exposures, severe provide critical insights developing broadly protective, multi-antigen, , T-cell-based, universal pan-Coronavirus vaccines capable conferring cross-species protection.

Language: Английский

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A Spike-Based mRNA Vaccine Encapsulated in Phospholipid 1,2-Dioleoyl-sn-Glycero-3-PhosphoEthanolamine Containing Lipid Nanoparticles Induced Potent B- and T-Cell Responses Associated with Protection Against SARS-CoV-2 Infection and COVID-19-like Symptoms in Hamsters

Vaccines, Journal Year: 2025, Volume and Issue: 13(1), P. 47 - 47

Published: Jan. 8, 2025

Background: Nucleoside-modified mRNA encapsulated in lipid nanoparticles (LNPs) have emerged as a promising vaccine strategy, especially for COVID-19. While the LNPs protect from degradation and efficiently deliver to antigen-presenting cells, effect of composition on immunogenicity protective efficacy mRNA/LNP vaccines is not well characterized. Studies using platform largely focused nucleic acid cargo with less attention paid LNP vehicle. Whether biophysical properties impact performance remains be fully elucidated. Methods: In present study, we used SARS-CoV-2 Spike-mRNA prototype study four different various compositions. Results: We demonstrate that when same was delivered LNP4 formulation based phospholipid 1,2-dioleoyl-sn-glycero-3-Phosphoethanolamine, it outperformed other (LNP1, LNP2, LNP3) are lipids. Compared three LNPs, (i) enhanced phenotypic functional maturation dendritic cells; (ii) induced strong T-cell responses; (iii) increased secretion proinflammatory cytokines pro-follicular T helper (Tfh) cell cytokines; (iv) higher neutralization IgG titers; (v) provided better protection against infection COVID-19-like symptoms hamster model. Furthermore, compared LNP-4 commercially available found provide immunity COVID-19 hamsters. Conclusion: This suggests Phospholipid 1,2-Dioleoyl-sn-Glycero-3-PhosphoEthanolamine containing Potent B- immunity. The mechanisms by which 1,2-Dioleoyl-sn-Glycero-3-PhosphoEthanolamine-based may activate B cells discussed.

Language: Английский

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Dynamics of spike-specific neutralizing antibodies across five-year emerging SARS-CoV-2 variants of concern reveal conserved epitopes that protect against severe COVID-19

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

Published: Feb. 18, 2025

Since early 2020, several SARS-CoV-2 variants of concern (VOCs) continue to emerge, evading waning antibody mediated immunity produced by the current Spike-alone based COVID-19 vaccines. This caused a prolonged and persistent pandemic that is going enter its fifth year. Thus, need remains for innovative next generation vaccines would incorporate protective Spike-derived B-cell epitopes resist immune evasion. Towards goal, in this study we (i) Screened sequences Spike among many VOCs identified conserved non-conserved linear epitopes; (ii) Compared titers neutralization antibodies specific these from serum symptomatic asymptomatic patients were exposed multiple across 5-year pandemic, (iii) efficacy versus against most pathogenic Delta variant "humanized" ACE-2/HLA transgenic mouse model. We found robust epitope-specific sera patients. In contrast, contained weaker responses epitopes. A multi-epitope vaccine incorporated epitopes, but not significantly protected ACE2/HLA mice infection like symptoms variant. These findings underscore importance generating severe various VOCs, providing valuable insights development broad-spectrum Coronavirus capable conferring cross-variant immunity.

Language: Английский

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Promising Cellular Immunotherapy for Colorectal Cancer Using Classical Dendritic Cells and Natural Killer T Cells

Cells, Journal Year: 2025, Volume and Issue: 14(3), P. 166 - 166

Published: Jan. 22, 2025

Colorectal cancer (CRC) remains one of the leading causes cancer-related morbidity and mortality around world. Despite advances in surgery, chemotherapy, targeted therapies, prognosis for patients with metastatic or advanced CRC poor. Immunotherapies comprising immune checkpoint inhibitors showed disappointing responses (mCRC). However, cellular immunotherapy, specifically using classical dendritic cells (cDCs), may hold unique promise recognition antigens. cDCs are substantial players instrumental orchestrating innate adaptive by processing presenting tumor antigens to effector cells. Natural killer T (NKT) insufficiently studied but because their ability bridge reactions crosstalk cancer. This review explores therapeutic potential both NKT as a synergistic therapy CRC, focusing on biological roles, strategies harnessing capabilities, clinical applications, challenges within microenvironment. Both can be used new effective approach cell-based therapies cancers provide hope that challenging treat.

Language: Английский

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Characterizing HLA-A2-restricted CD8+ T-cell epitopes and immune responses to Omicron variants in SARS-CoV-2-inactivated vaccine recipients

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

Published: March 18, 2025

Recent surveillance has identified the emergence of SARS-CoV-2 Omicron ariant, which exhibits ability to evade multiple neutralizing antibodies generated by prior infection or vaccination. However, significant knowledge gaps remain regarding CD8 T-cell immune reactivity variant. This study aims evaluate characteristics HLA-A2-restricted epitopes from variant and analyze epitope-specific responses inactivated vaccines. We conducted a comprehensive analysis vaccines, focusing on derived Mutant were evaluated for their impact antigen presentation reactivity. Additionally, we screened that exhibited reduced following Our findings revealed mutant in led escape diminished responses. two associated with decreased post-Omicron emergence. Notably, discovered an S protein epitope, 67A>V, demonstrated similar proportions specificity between ancestral strains, suggesting its conservation potential immunogenicity vaccine development. Furthermore, third dose significantly increased number T cells, underscoring importance booster doses enhancing cellular against highlights through epitope mutations, while also identifying conserved utility design. The observed increase cells emphasizes critical role additional vaccinations strengthening immunity emerging variants. These provide valuable insights development next-generation vaccines targeting optimizing strategies.

Language: Английский

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Therapeutic mucosal vaccination of herpes simplex virus type 2 infected guinea pigs with an adenovirus-based vaccine expressing the ribonucleotide reductase 2 and glycoprotein D induces local tissue-resident CD4+ and CD8+ TRM cells associated with protection against recurrent genital herpes

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

Published: March 26, 2025

Introduction The reactivation of herpes simplex virus 2 (HSV-2) from latency causes viral shedding that develops into recurrent genital lesions. role tissue-resident T cells and the nature antigens associated with protection against remain to be fully elucidated. Methods In this preclinical study, we investigated protective therapeutic efficacy, in guinea pig model herpes, five recombinant adenovirus-based vaccine candidates (rAd-Ags), each expressing different HSV-2 envelope tegument proteins: RR1 (UL39), RR2 (UL40), gD (glycoprotein D), VP16 (UL48), or VP22 (UL49). We compared frequency function dorsal root ganglia (DRG)- vaginal mucosa (VM)-resident CD4+ CD8+ induced by their effect on severity herpes. Results latent-infected pigs immunized rAd-RR2 rAd-gD vaccines showed high frequencies DRG- VM-tissue-resident IFN-g-producing TRM significant reductions herpetic Discussion Taken together, these results provide new insights cell mechanisms confirm protein glycoprotein D as viable candidate incorporated future vaccines.

Language: Английский

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Role of inflammasomes in cancer immunity: mechanisms and therapeutic potential

Journal of Experimental & Clinical Cancer Research, Journal Year: 2025, Volume and Issue: 44(1)

Published: March 29, 2025

Inflammasomes are multi-protein complexes that detect pathogenic and damage-associated molecular patterns, activating caspase-1, pyroptosis, the maturation of pro-inflammatory cytokines such as IL-1β IL-18Within tumor microenvironment, inflammasomes like NLRP3 play critical roles in cancer initiation, promotion, progression. Their activation influences crosstalk between innate adaptive immunity by modulating immune cell recruitment, cytokine secretion, T-cell differentiation. While can contribute to growth metastasis through chronic inflammation, their components also present novel therapeutic targets. Several inhibitors targeting inflammasome components- sensor proteins (e.g., NLRP3, AIM2), adaptor ASC), downstream cytokines- being explored modulate activity. These strategies aim activity enhance anti-tumor responses improve clinical outcomes. Understanding role is crucial for developing interventions effectively bridge better

Language: Английский

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A Pan-Beta-Coronavirus Vaccine Bearing Conserved and Asymptomatic B- and T-Cell Epitopes Protect Against Highly Pathogenic Delta and Highly Transmissible Omicron SARS-CoV-2 Variants of Concern

Published: April 15, 2025

ABSTRACT SARS CoV-2 continues to evolve into new viral variants due mutation, primarily in the Spike protein. Existing Spike-based vaccines are less effective because these can be more transmissible and evade vaccine-induced immunity. By targeting conserved, Spike, non-Spike, antigens using both arms of adaptive immune system, i.e. B T cells, we aim reduce reliance on neutralizing antibodies avoid potential mismatches between COVID-19 circulating virus strains. In this way, enhanced memory function broad-spectrum protection against existing evolving attained. We have developed a mRNA-LNP-based multi-epitope vaccine incorporating conserved CD8 + T-cell, CD4 B-cell epitopes. These epitopes were selected as being highly recognized by B- T-cells from unvaccinated asymptomatic patients. To evaluate effectiveness “asymptomatic” vaccine, utilized novel triple transgenic h-ACE-2-HLA-A2/DR mouse model enable assessment human cell Key observations include induction of: ( i ) robust infection disease caused SARS-CoV-2 Delta (B.1.617.2) Omicron (XBB.1.5) variants, measured reduced weight loss, replication, lung pathology; ii strong antibody responses,; iii potent epitope-specific IFN-γ-producing /CD8 cells Follicular helper (T FH cells. data support strategy B-cells directed toward epitopes, structural non-structural protein antigens, generate protective immunity minimize impact across multiple variants.

Language: Английский

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A multi-epitope/CXCL11 prime/pull coronavirus mucosal vaccine boosts the frequency and the function of lung-resident memory CD4 ⁺ and CD8 ⁺ T cells and enhanced protection against COVID-19-like symptoms and death caused by SARS-CoV-2 infection

Journal of Virology, Journal Year: 2023, Volume and Issue: 97(12)

Published: Dec. 1, 2023

Although the current rate of SARS-CoV-2 infections has decreased significantly, COVID-19 still ranks very high as a cause death worldwide. As October 2023, weekly mortality is at 600 deaths in United States alone, which surpasses even worst rates recorded for influenza. Thus, long-term outlook serious concern outlining need next-generation vaccine. This study found that prime/pull coronavirus vaccine strategy increased frequency functional SARS-CoV-2-specific CD4

Language: Английский

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