Adjuvant-free nanofiber vaccine induces in situ lung dendritic cell activation and T _H 17 responses

Abstract

The current paradigm that subunit vaccines require adjuvants to optimally activate innate immunity implies that increased vaccine reactogenicity will invariably be linked to improved immunogenicity. Countering this paradigm, nanoparticulate vaccines have been reported to act as delivery systems for vaccine antigens and induce immunity without the need for exogenous adjuvants or local inflammation; however, the mechanisms underlying the immunogenicity of nanoparticle vaccines are incompletely identified. Here, we show that antigens displayed on self-assembling nanofiber scaffolds and delivered intranasally are presented by CD103+ and CD11b+ lung dendritic cells that up-regulate CD80 and migrate into the draining lymph node (LN). This was accompanied by a nearly exclusive priming and accumulation of antigen-specific TH17 cells occurring independently in both LN and lung. Thus, self-assembling peptide nanofiber vaccines may represent a novel, needle- and adjuvant-free means of eliciting protective immunity against fungal and bacterial infections at skin and mucosal barrier surfaces.

Full Spectrum Flow Cytometry as a Powerful Technology for Cancer Immunotherapy Research

“…The FSFC technology enables both structural and functional characterization of immune cells for vaccine studies, including dendritic cell antigen presentation and migration to lymph node and polarization and proliferation of effector T cells, by quantifying the expression of multiple transcriptional factors T-bet, Gata3, RORγt, Bcl6, Foxp3. Si et al designed an adjuvant-free nano vaccine that induces in situ lung dendritic cell activation and accumulation of antigen-specific Th17 T cells in lymph node and lung, with subsequent induction of a protective response (Si et al, 2020). The study by Bommireddy et al showed that a vaccine using tumor membrane vesicles (TMV), enhances the efficacy of anti-PD1 immune checkpoint treatment in inhibitor-resistant squamous cell carcinoma.…”

Biomaterial-based immunoengineering to fight COVID-19 and infectious diseases

“…47 This nanofiber vaccine can be administered intranasally to promote expansion of tissue-resident immune cells. 48…”

Current Perspective on Nasal Delivery Systems for Chronic Rhinosinusitis

“…The morphology and diameter of the nanofibers were also fine-tuned to influence the controlled drug release [160]. Youhui et al [14] showed that intranasal self-assembled peptide nanofiber vaccines may be a new, needle-free, and adjuvant-free method to induce protective immunity against bacterial and fungal infections involving skin and mucosal barrier surfaces. Most recently, Gholizadeh et al [161] combined a new carbon nanofiber modified carbon electrode with a human nasal epithelial mucosa on a chip to achieve real-time quantitative monitoring of nasal administration in vitro.…”

“…In addition, seawater, which contains natural minerals and oligo-elements, is also used for nasal irrigation. A meta-analysis comparing hypertonic saline irrigation with isotonic saline irrigation reported that patients with sinusitis benefited more with improved symptoms from hypertonic saline irrigation than from isotonic saline irrigation, especially in the younger population [ 14 ]. Another meta-analytic study recently claimed that hypertonic saline irrigation is more effective in treating CRS; however, there was no difference in smell improvement compared to isotonic saline irrigation [ 15 ].…”