Abstract
Synthetic vaccines utilize viral signatures to trigger immune responses. Although the immune responses raised against the biochemical signatures of viruses are well characterized, the mechanism of how they affect immune response in the context of physical signatures is not well studied. In this work, we investigated the ability of zero- and one-dimensional self-assembled peptide nanostructures carrying unmethylated CpG motifs (signature of viral DNA) for tuning immune response. These nanostructures represent the two most common viral shapes, spheres and rods. The nanofibrous structures were found to direct immune response towards Th1 phenotype, which is responsible for acting against intracellular pathogens such as viruses, to a greater extent than nanospheres and CpG ODN alone. In addition, nanofibers exhibited enhanced uptake into dendritic cells compared to nanospheres or the ODN itself. The chemical stability of the ODN against nuclease-mediated degradation was also observed to be enhanced when complexed with the peptide nanostructures. In vivo studies showed that nanofibers promoted antigen-specific IgG production over 10-fold better than CpG ODN alone. To the best of our knowledge, this is the first report showing the modulation of the nature of an immune response through the shape of the carrier system.
Highlights
Bacterial/viral DNAs, have been studied in great deal and demonstrated to boost humoral and cellular immune responses to vaccines[9,10,11,12]
Non-aggregating CpG ODNs are known to be poor interferon inducers, while being strong inducers of IL-6 production and expression of maturation markers on the cell surface[11,25]. This contrast results from the differing subcellular localization of nanoparticulate and soluble CpG ODNs in plasmacytoid dendritic cells and induction of distinct signaling pathways[26]. All of these studies suggest that the morphology of a vehicle has a strong effect in shaping the immune response raised by the biochemical signals it carries
We compared the immune responses raised against CpG DNA delivered by zero- and one- dimensional nanostructures formed by the self-assembly of peptide amphiphile molecules and CpG ODNs (Fig. 1)
Summary
Bacterial/viral DNAs, have been studied in great deal and demonstrated to boost humoral and cellular immune responses to vaccines[9,10,11,12]. This contrast results from the differing subcellular localization of nanoparticulate and soluble CpG ODNs in plasmacytoid dendritic cells and induction of distinct signaling pathways[26] All of these studies suggest that the morphology of a vehicle (virus or synthetic vaccine particle) has a strong effect in shaping the immune response raised by the biochemical signals (such as viral DNA or antigen) it carries. A systematic investigation of how the mammalian immune system responds to viral biochemical signals in the context of main viral shapes-spheres and rods-is not available in the literature To answer this question, we compared the immune responses raised against CpG DNA delivered by zero- and one- dimensional nanostructures formed by the self-assembly of peptide amphiphile molecules and CpG ODNs (Fig. 1). The present work concerns the design of virus-like nanostructures capable of potently eliciting anti-viral immune responses and the modulation of the immune responses against CpG DNA through changes in physical properties of the delivery system (Fig. 1)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
