Currently approved influenza vaccines predominantly protect through antibodies directed against the highly variable glycoprotein hemagglutinin (HA), necessitating annual redesign and formulation based on epidemiological prediction of predominant circulating strains. More conserved influenza protein sequences, such as the ectodomain of the influenza M2 protein, or M2e, show promise as a component of a universal influenza A vaccine, but require a Th1-biased immune response for activity. Recently, recombinant, bacterially derived outer membrane vesicles (OMVs) demonstrated potential as a platform to promote a Th1-biased immune response to subunit antigens. Here, we engineer three M2e-OMV vaccines and show that all elicit strong IgG titers, with high IgG2a:IgG1 ratios, in BALB/c mice. Additionally, the administration of one M2e-OMV construct containing tandem heterologous M2e peptides (M2e4xHet-OMV) resulted in 100% survival against lethal doses of the mouse-adapted H1N1 influenza strain PR8. Passive transfer of antibodies from M2e4xHet-OMV vaccinated mice to unvaccinated mice also resulted in 100% survival to challenge, indicating that protection is driven largely via antibody-mediated immunity. The potential mechanism through which M2e-OMVs initiated the immune response was explored and it was found that the constructs triggered TLR1/2, TLR4, and TLR5. Our data indicate that OMVs have potential as a platform for influenza A vaccine development due to their unique adjuvant profile and intrinsic pathogen-mimetic nature.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.vaccine.2016.01.028 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Isatidis root polysaccharides ameliorates post-weaning diarrhea by promoting intestinal health and modulating the gut microbiota in piglets.
Vet Q
December 2025
Animal Nutritional Genome and Germplasm Innovation Research Center, College of Animal Science and Technology, Hunan Agricultural University, Changsha, China.
This study aimed to investigate the effects of dietary isatidis root polysaccharide (IRP) on diarrhea, immunity, and intestinal health in weanling piglets. Forty healthy piglets were randomly assigned to five groups receiving varying dosages of IRP. The findings indicated that different concentrations of IRP significantly reduced diarrhea scores ( < 0.
View Article and Find Full Text PDFBiomathematical enzyme kinetics model of prebiotic autocatalytic RNA networks: degenerating parasite-specific hyperparasite catalysts confer parasite resistance and herald the birth of molecular immunity.
PLoS Comput Biol
January 2025
Genesupport, Avenue de Sévelin 18, Lausanne, Switzerland.
Catalysis and specifically autocatalysis are the quintessential building blocks of life. Yet, although autocatalytic networks are necessary, they are not sufficient for the emergence of life-like properties, such as replication and adaptation. The ultimate and potentially fatal threat faced by molecular replicators is parasitism; if the polymerase error rate exceeds a critical threshold, even the fittest molecular species will disappear.
View Article and Find Full Text PDFExplainable Machine Learning to Predict Treatment Response in Advanced Non-Small Cell Lung Cancer.
JCO Clin Cancer Inform
January 2025
Emory University School of Medicine, Atlanta, GA.
Purpose: Immune checkpoint inhibitors (ICIs) have demonstrated promise in the treatment of various cancers. Single-drug ICI therapy (immuno-oncology [IO] monotherapy) that targets PD-L1 is the standard of care in patients with advanced non-small cell lung cancer (NSCLC) with PD-L1 expression ≥50%. We sought to find out if a machine learning (ML) algorithm can perform better as a predictive biomarker than PD-L1 alone.
View Article and Find Full Text PDFGlutathione-Responsive Metal-Organic-Framework-Derived MnO/(A/R)TiO Nanoparticles for Enhanced Synergistic Sonodynamic/Chemodynamic/Immunotherapy.
ACS Nano
January 2025
State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun 130012, China.
Despite the potential of sonodynamic therapy (SDT) in treating malignant tumors, the lack of effective sonosensitizers has limited its clinical implementation. In this study, we explored the relationship between the heteroatom doping concentration in metal-organic frameworks and interface formation after pyrolysis by regulating the addition of manganese sources and successfully derived Z-scheme heterojunctions MnO/(A/R)TiO (MTO) in situ from MIL-125-NH (Ti/Mn). The electron transfer pathway introduced by interfacial contact promoted carrier separation and greatly preserved the effective redox components, significantly influencing the performance of reactive oxygen species generation.
View Article and Find Full Text PDFInnate Immune Activation with Multifunctional Nanoparticles for Cancer Immunotherapy.
Angew Chem Int Ed Engl
January 2025
University of Chicago Division of the Physical Sciences, chemistry, UNITED STATES OF AMERICA.
Immune checkpoint blockade (ICB) has revolutionized the treatment of many cancers by leveraging the immune system to combat malignancies. However, its efficacy is limited by the immunosuppressive tumor microenvironment and other regulatory mechanisms of the immune system. Innate immune modulators (IIMs) provide potent immune activation to complement adaptive immune responses and help overcome resistance to ICB.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!