Published: Sept. 22, 2023
Language: Английский
Molecular Therapy — Methods & Clinical Development, Journal Year: 2024, Volume and Issue: 32(3), P. 101325 - 101325
Published: Aug. 19, 2024
The effectiveness of mRNA vaccines largely depends on their lipid nanoparticle (LNP) component. Herein, we investigate the DLin-KC2-DMA (KC2) and SM-102-based LNPs for intramuscular delivery a plasmid encoding B.1.617.2 (Delta) spike fused with CD40 ligand. LNP encapsulation this CD40L-adjuvanted DNA vaccine either formulation drastically enhanced antibody responses, enabling neutralization heterologous Omicron variants. DNA-LNP formulations provided excellent protection from homologous challenge, reducing viral replication, preventing histopathological changes in pulmonary tissues. Moreover, maintained high level against BA.5 challenge despite reduced neutralizing response. In addition, observed that vaccination led to downregulation interferon signaling, interleukin-12 macrophage response pathways following SARS-CoV-2 shedding some light mechanisms underlying prevention injury. These results highlight potential combination molecular adjuvants LNP-based induce greater broader immune responses capable inflammatory damage protecting emerging findings could be informative future design both vaccines.Graphical abstract
Language: Английский
Citations
1
ACS Central Science, Journal Year: 2024, Volume and Issue: 10(10), P. 1871 - 1884
Published: Sept. 17, 2024
The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein is main target neutralizing antibodies. Although they are infrequently elicited during infection or vaccination, antibodies that bind to conformation-specific cryptic face RBD display remarkable breadth binding and neutralization across
Language: Английский
Citations
1
Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)
Published: Nov. 28, 2024
Abstract Various public health measures have contained outbreaks of SARS-CoV-2, but concerns remain over the possibility future surges. Improvements in broadening vaccine response can stifle new and nascent infections. In this study, we tested effects different adjuvant combinations on immunization mice with receptor-binding domain (RBD)-containing S1-subunit spike protein (S1 protein) from SARS-CoV-2 to induce a robust humoral cellular immune response. We showed that subcutaneous S1 co-delivered IL-15 TLR-ligands (MALP-2, poly I: C, CpG) or IL-12 GM-CSF DOTAP, Alum induced significantly high titers durable antibodies, predominantly IgG1, IgG2a, IgG2b, could bind RBD, S1-subunit, full-length ectodomain sera compared alone both B6 wild-type (WT) K18-hACE2 transgenic mice. addition, antibody responses against aged mice, younger reduced plaque formation live had effective binding ten variants including Omicron (B.1.1.529), greater neutralization activity as early day 21 post-immunization measured by inhibition RBD hACE2 than immunized Alum. also identified antibody-binding epitopes using 18-mer peptides 9-residue overlaps protein. CD8 + T-cell specific peptide pools were observed up 200 tetramer staining. These data show efficacy immunologically targeted adjuvants for increasing immunogenicity contribute more vaccines.
Language: Английский
Citations
1
International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(20), P. 12514 - 12514
Published: Oct. 19, 2022
The serious clinical course of SARS-CoV-2 infection is usually accompanied by acute kidney injury (AKI), worsening prognosis and increasing mortality. AKI in COVID-19 above all a consequence systemic dysregulations leading to inflammation, thrombosis, vascular endothelial damage necrosis. All these processes rely on the interactions between innate immunity elements, including circulating blood cells, resident renal their cytokine products, complement systems, coagulation cascades contact systems. Numerous simultaneous pathways should secure an effective host defense. Since they form network cross-linked auto-amplification loops, uncontrolled activation possible. When actions selected amplify, cascade evades control propagation inflammation necrosis worsens, overactivity immunothrombosis. reaches kidney, where affecting single tubular cells spreads through tissue collateral triggers AKI. This review attempt synthetize connections components engaged COVID-19-related summarize knowledge pathophysiological background responsible for damage.
Language: Английский
Citations
4
Medwave, Journal Year: 2023, Volume and Issue: 23(11), P. e2787 - e2787
Published: Dec. 20, 2023
Based on the recommendations of Vaccine Advisory Committee and National Immunization Program, Chile implemented an early vaccination process population with vaccines from different laboratories. The study neutralizing antibody levels in subgroups contributes to establishment correlates protection against SARS-CoV-2 infection. In 2022 2023 we set up a community cohort 914 adults cardiovascular risk factors. this are measuring humoral immune response exposure antigens, either by or infection, as well incidence COVID-19 other adverse events. This cohort, which call COmmunity Cohort, is providing us valuable information antibodies these individuals their degree COVID-19.A partir de las recomendaciones emanadas del Comité Asesor en Vacunas y el Programa Nacional Inmunizaciones, implementó precozmente un proceso vacunación la población con vacunas provenientes diferentes laboratorios. El estudio los niveles anticuerpos neutralizantes subgrupos poblacionales, contribuye al establecimiento correlatos protección frente infección por SARS-CoV-2. En establecimos una cohorte comunitaria adultos factores riesgo cardiovascular. esta estamos midiendo respuesta inmune exposición antígenos SARS-CoV-2, ya sea o infección, así como incidencia otros eventos adversos. Esta cohorte, que llamamos, nos está entregando valiosa información sobre estas personas su grado COVID-19.
Citations
2
Emerging Microbes & Infections, Journal Year: 2023, Volume and Issue: 12(1)
Published: March 16, 2023
First-generation SARS-CoV-2 vaccines based on different platforms have significantly reduced hospitalization and death. However, the constant evolution of has only prolonged global pandemic. Recent emergence Omicron subvariants XBB BQ.1.1 posed an unprecedented challenge to efficacy current broad-spectrum vaccines. Several lines evidence demonstrated that majority therapeutic monoclonal neutralizing antibodies (NAbs) lost their activities against [1,2]. Dramatic decline antibody titer was founded in sera from vaccinees infected persons [2,3]. Some subvariants, such as BQ.1.1, are even more resistant than SARS-CoV NAbs elicited by ancestral strain, although there about 50 amino acids between RBDs strain SARS-CoV, 21 suggesting pandemic remarkably promoted immune escape mutations some subvariants. This calls for development a novel immunization strategy prevent infection dominantly circulating variants with exceptional resistance vaccines, BQ.1.1.
Language: Английский
Citations
1
Vaccines, Journal Year: 2023, Volume and Issue: 11(5), P. 1002 - 1002
Published: May 20, 2023
Developing variant vaccines or multivalent is a feasible way to address the epidemic as SARS-CoV-2 variants of concern (VOCs) posed an increased risk global public health. The spike protein virus was usually used main antigen in many types produce neutralizing antibodies against virus. However, (S) proteins different were only differentiated by few amino acids, making it difficult obtain specific that can distinguish VOCs, thereby challenging accurate distinction and quantification using immunological methods such ELISA. Here, we established method based on LC-MS quantify S inactivated monovalent trivalent (prototype, Delta, Omicron strains). By analyzing sequences prototype, strains, identified peptides among three strains synthesized them references. synthetic isotopically labeled internal targets. Quantitative analysis performed calculating ratio between reference target. verification results have shown had good specificity, accuracy, precision. This not accurately vaccine but also could be applied each strain vaccines. Hence, this study quality control variation enabling more quantification, will help improve protection some extent.
Language: Английский
Citations
1
Journal of Medical Virology, Journal Year: 2024, Volume and Issue: 96(1)
Published: Jan. 1, 2024
Abstract The use of precise epitope peptides as antigens is essential for accurate serological diagnosis viral‐infected individuals, but now it remains an unsolvable problem mapping B cell epitopes (BCEs) recognized by human serum. To address this challenge, we propose a novel delimitation (ED) method to uncover BCEs in the delineated IgG‐reactive (HR) antigenic (APs). Specifically, based on rationale similarities humoral immune responses between mammalian species consists pair elements: experimentally HR‐AP and rabbit‐recognized (RR) BCE motif corresponding sequence alignment analysis. As result using ED approach, after decoding four RR‐epitomes papillomavirus types 16/18‐E6 E7 proteins utilizing rabbit serum against each recombinant protein analysis HR‐APs RR‐BCEs, 19 fine 17 22 known were defined RR‐BCE motifs, including type‐specificity delimited homologous proteins. test with 16/20mer demonstrated that effective efficient, indicating can be used alternative conventional identification overlapping 8mer peptides.
Language: Английский
Citations
0
Viruses, Journal Year: 2024, Volume and Issue: 16(3), P. 484 - 484
Published: March 21, 2024
Severe acute respiratory syndrome (SARS)-coronavirus (CoV), Middle Eastern (MERS)-CoV, and SARS-CoV-2 have seriously threatened human life in the 21st century. Emerging re-emerging β-coronaviruses after coronavirus disease 2019 (COVID-19) epidemic remain possible highly pathogenic agents that can endanger health. Thus, pan-β-coronavirus vaccine strategies to combat upcoming dangers are urgently needed. In this study, four LNP-mRNA vaccines, named O, D, S, M, targeting spike protein of Omicron, Delta, SARS-CoV, MERS-CoV, respectively, were synthesized characterized for purity integrity. All LNP-mRNAs induced effective cellular humoral immune responses against corresponding antigens mice. Furthermore, S D neutralizing antibodies SARS-CoV SARS-CoV-2, which failed cross-react with MERS-CoV. Subsequent evaluation sequential cocktail immunizations M effectively elicited broad immunity variants, A direct comparison regimens indicated vaccination strategy more potent T-cell heterotypic viruses as well broader antibody activity pan-β-coronaviruses. Overall, these results present a potential improved preparedness prior future threats.
Language: Английский
Citations
0
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown
Published: June 5, 2024
The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein is main target neutralizing antibodies. Although they are infrequently elicited during infection or vaccination, antibodies that bind to conformation-specific cryptic face RBD display remarkable breadth binding and neutralization across
Language: Английский
Citations
0