A Broad-Spectrum Multi-Antigen mRNA/LNP-Based Pan-Coronavirus Vaccine Induced Potent Cross-Protective Immunity Against Infection and Disease Caused by Highly Pathogenic and Heavily Spike-Mutated SARS-CoV-2 Variants of Concern in the Syrian Hamster Model

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

Published: Feb. 15, 2024

ABSTRACT The first-generation Spike-alone-based COVID-19 vaccines have successfully contributed to reducing the risk of hospitalization, serious illness, and death caused by SARS-CoV-2 infections. However, waning immunity induced these failed prevent immune escape many variants concern (VOCs) that emerged from 2020 2024, resulting in a prolonged pandemic. We hypothesize next-generation Coronavirus (CoV) vaccine incorporating highly conserved non-Spike antigens would confer stronger broader cross-protective against multiple VOCs. In present study, we identified ten are 8.7 million strains, twenty-one VOCs, SARS-CoV, MERS-CoV, Common Cold CoVs, animal CoVs. Seven 10 were preferentially recognized CD8 + CD4 T-cells unvaccinated asymptomatic patients, irrespective VOC infection. Three out seven T cell belong early expressed Replication Transcription Complex (RTC) region, when administered golden Syrian hamsters, combination with Spike, as nucleoside-modified mRNA encapsulated lipid nanoparticles (LNP) (i.e., combined mRNA/LNP-based pan-CoV vaccine): ( i ) Induced high frequencies lung-resident antigen-specific CXCR5 follicular helper (T FH cells, GzmB cytotoxic cells CYT ), CD69 IFN-γ TNFα effector EFF ); ii Reduced viral load COVID-19-like symptoms various including pathogenic B.1.617.2 Delta variant transmittable heavily Spike-mutated XBB1.5 Omicron sub-variant. could be rapidly adapted for clinical use emerging mutated IMPORTANCE As January over 1500 individuals United States alone still dying each week despite implementation vaccines. emergence transmissible (VOCs), such currently circulating BA.2.86 JN.1 sub-variants, constantly overrode Here report next generation broad spectrum multi-antigen consists delivers three protein together Spike B-cell antigen. Compared side-by-side clinically proven Spike-alone vaccine, vaccine-induced higher specific-neutralizing antibodies. This was associated potent cross-reactive protection sub-variants. Our findings suggest an alternative broad-spectrum pan-Coronavirus capable disrupting current booster paradigm; outpacing bivalent variant-adapted vaccines; iii ending apparent

Language: Английский

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Effects of different antiviral mouthwashes on the surface roughness, hardness, and color stability of composite CAD/CAM materials

Journal of Applied Biomaterials & Functional Materials, Journal Year: 2024, Volume and Issue: 22

Published: Jan. 1, 2024

Objective: To evaluate the effect of COVID-19 preventive mouthwashes on surface hardness, roughness (Ra), and color change (ΔE) three different polymer-based composite CAD/CAM materials (Vita Enamic (ENA), Grandio Block (GB), Lava Ultimate (LU)). Methods: A total 100 rectangular-shaped specimens with dimensions 2 mm × 7 12 were obtained by sectioning blocks randomly divided into five subgroups according to 30 days mouthwash immersion protocol as follows: Control: artificial saliva, PVP-I: 1% povidone-iodine, HP: 1.5% hydrogen peroxide, CPC: containing 0.075% cetylpyridinium chloride, EO: essential oils. Microhardness, Ra, ΔE values measured at baseline after protocols. Data analyzed using Wald Chi-square, two-way ANOVA, post hoc Tukey tests. Results: The independent factors (materials solutions) significantly influenced microhardness ( p < 0.001). Ra was not affected any > 0.05). each material varied in PvP-I HP highest percentage microhardness, found LU immersed mouthwashes, while lowest ENA groups Conclusion: Within limitations this study, it that hardness tested are susceptible degradation mouthwashes.

Language: Английский

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Enhanced Assessment of Cross-Reactive Antigenic Determinants within the Spike Protein

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(15), P. 8180 - 8180

Published: July 26, 2024

Despite successful vaccination efforts, the emergence of new SARS-CoV-2 variants poses ongoing challenges to control COVID-19. Understanding humoral responses regarding infections and their impact is crucial for developing future vaccines that are effective worldwide. Here, we identified 41 immunodominant linear B-cell epitopes in its spike glycoprotein with an SPOT synthesis peptide array probed a pool serum from hospitalized COVID-19 patients. The bioinformatics showed restricted set unique compared other coronavirus family members. Potential crosstalk was also detected Dengue virus (DENV), which confirmed by screening individuals infected DENV before pandemic commercial ELISA anti-SARS-CoV-2 antibodies. A high-resolution evaluation antibody reactivity against peptides representing protein ten sequences NTD, RBD, S2 domains. Functionally, antibody-dependent enhancement (ADE) monocytes observed vitro pre-pandemic Dengue-positive sera. significant increase viral load measured controls, no detectable neutralization or considerable cell death, suggesting role entry. Cross-reactivity proteins This study highlights importance identifying specific generated during response pathogenic infection understand potential interplay previous on diseases vaccinations immunodiagnostics.

Language: Английский

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Immunological Considerations for the Development of an Effective Herpes Vaccine

Microorganisms, Journal Year: 2024, Volume and Issue: 12(9), P. 1846 - 1846

Published: Sept. 6, 2024

Research is underway to develop a vaccine prevent and cure infection from herpes simplex virus (HSV). It emphasizes the critical need for immunization address public health issues shortcomings of existing treatment options. Furthermore, studies on HSV advance field immunology creation, which may help in battle against other viral illnesses. The current lack such is, part, due latency sensory ganglions. Current vaccines rely tissue-resident memory CD8

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

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

Published: Sept. 25, 2024

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 (

Language: Английский

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Spike mRNA Vaccine Encapsulated in a Lipid Nanoparticle Composed of Phospholipid 1,2-Dioleoyl-sn-Glycero-3-Phosphoethanolamine Induced Potent B- and T-cell Responses Associated with Protection against COVID-19 in Hamsters

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

Published: Oct. 7, 2024

ABSTRACT Lipid nanoparticles (LNPs) have recently emerged as one of the most advanced vehicle platforms for efficient in vivo delivery nucleoside-modified mRNA vaccine, particularly COVID-19. LNPs comprise four different lipids: ionizable lipids, helper or neutral cholesterol, and lipids attached to polyethylene glycol (PEG). Studies on using mRNA-LNP platform vaccines largely focused nucleic acid cargo with less attention LNP vehicle. While protect from degradation efficiently deliver antigen-presenting cells effect lipid composition biophysical properties immunogenic protective vaccine remain be fully elucidated. In present study, we used SARS-CoV-2 Spike-mRNA a prototype study 4 various compositions. We demonstrate that when same was delivered LNP4 formulation based phospholipid 1,2-dioleoyl-sn-glycero-3- Phosphoethanolamine it outperformed immunogenicity efficacy three (LNP1, LNP2, LNP3) are lipids. Compared other LNPs, LNP4: ( i ) enhanced phenotypic functional maturation dendritic cells; ii induced strong T-cell responses, iii increased secretion proinflammatory, pro-follicular T (Tfh) cell cytokines; iv higher neutralization IgG titers; v provided better protection against infection COVID-19 hamster model. discussed potential mechanisms by which include 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine may activate B- responses.

Language: Английский

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Production and evaluation of a bivalent adjuvant inactivated vaccine against infectious hematopoietic necrosis virus and infectious pancreatic necrosis virus

Aquaculture, Journal Year: 2024, Volume and Issue: unknown, P. 741914 - 741914

Published: Nov. 1, 2024

Language: Английский

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A Universal Multi-Epitope Vaccine Design Against Porcine Reproductive and Respiratory Syndrome Virus via Bioinformatics and Immunoinformatics Approaches

Veterinary Sciences, Journal Year: 2024, Volume and Issue: 11(12), P. 659 - 659

Published: Dec. 16, 2024

Porcine reproductive and respiratory syndrome virus (PRRSV) causes disorders in sows severe pneumonia piglets, alongside immunosuppressive effects on the host. It poses a significant global threat to swine industry, with no effective control measures currently available due its complex pathogenesis high variability. Conventional inactivated attenuated vaccines provide inadequate protection carry biosafety risks. In this study, we designed universal multi-epitope peptide vaccine against PRRSV using bioinformatics immunoinformatics approaches address these limitations. By selecting sequences from seven representative strains, predicted highly conserved immunogenic T cell (Th CTL) epitopes across all encoded proteins. These were rationally concatenated reported B neutralizing into construct. We performed comprehensive assessments of construct’s physicochemical biochemical properties, along predictions refinements secondary tertiary structures. Molecular docking simulations TLR2 TLR4 revealed strong potential binding interactions. Immune indicated that could induce robust humoral cellular immune responses. This study provides scientific foundation for development safe subunit offers new perspectives designing other viral diseases.

Language: Английский

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Antigen Delivery Platforms for Next-Generation Coronavirus Vaccines

Vaccines, Journal Year: 2024, Volume and Issue: 13(1), P. 30 - 30

Published: Dec. 31, 2024

The COVID-19 pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is in its sixth year and being maintained inability of current spike-alone-based vaccines to prevent transmission leading continuous emergence variants sub-variants concern (VOCs). This underscores critical need for next-generation broad-spectrum pan-Coronavirus (pan-CoV vaccine) break this cycle end pandemic. development a pan-CoV vaccine offering protection against wide array VOCs requires two key elements: (1) identifying protective antigens that are highly conserved between passed, current, future VOCs; (2) developing safe efficient antigen delivery system induction broad-based long-lasting B- T-cell immunity. review will present state platforms involving multifaceted approach, including bioinformatics, molecular structural biology, immunology, advanced computational methods; discuss challenges facing effective platforms; (3) highlight potential nucleoside-modified mRNA encapsulated lipid nanoparticles (LNP) as platform well suited needs vaccine, such ability induce immunity amenable large-scale manufacturing safely provide durable threats.

Language: Английский

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