Abstract
Pulmonary administration of biomimetic nanoparticles loaded with antigen may represent an effective strategy to directly modulate adaptive immune responses in the respiratory tract. Depending on the design, virosomes may not only serve as biomimetic antigen carriers but are also endowed with intrinsic immune-stimulatory properties. We designed fluorescently labeled influenza-derived virosomes and liposome controls coupled to the model antigen ovalbumin to investigate uptake, phenotype changes, and antigen processing by antigen-presenting cells exposed to such particles in different respiratory tract compartments. Both virosomes and liposomes were captured by pulmonary macrophages and dendritic cells alike and induced activation in particle-bearing cells by upregulation of costimulatory markers such as CD40, CD80, CD86, PD-L1, PD-L2, and ICOS-L. Though antigen processing and accumulation of both coupled and soluble antigen was similar between virosomes and liposomes, only ovalbumin-coupled virosomes generated a strong antigen-specific CD4+ T cell proliferation. Pulmonary administrated antigen-coupled virosomes therefore effectively induced adaptive immune responses and may be utilized in novel preventive or therapeutic approaches in the respiratory tract.
Highlights
Immune modulation in the lung may represent a direct approach for treating respiratory disorders such as allergic asthma [1, 2], given that the respiratory tract is readily accessible, making it an ideal target for non-invasive treatments
Size and homogeneity were measured by dynamic light scattering and by nanoparticle tracking analysis (NTA), routinely providing a diameter of 90–100 nm
We investigated whether stronger T cell proliferation with OVA-coupled virosomes was due to dendritic cells (DCs) activation in lung-draining lymph nodes (LDLNs) and whether uptake of nanocarriers induced phenotypic changes in respiratory tract macrophage and DC populations
Summary
Immune modulation in the lung may represent a direct approach for treating respiratory disorders such as allergic asthma [1, 2], given that the respiratory tract is readily accessible, making it an ideal target for non-invasive treatments. Biomedical nanoparticles for targeted delivery of antigen for vaccinations have been developed [5,6,7], but to date there is insufficient understanding on how such nanoparticles interact with immune cells in the lung. Biomimetic nanoparticles such as virosomes and liposomes have already been approved for human use due to their advantageous safety profile and tolerance [8,9,10]. HA binds to sialic acid residues that are abundantly expressed on DCs and macrophages [20], thereby triggering highly efficient receptor-mediated uptake
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