Abstract
Development of vaccines in autoimmune diseases has received wide attention over the last decade. However, many vaccines showed limited clinical efficacy. To enhance vaccine efficacy in infectious diseases, biocompatible and biodegradable polymeric nanoparticles have gained interest as antigen delivery systems. We investigated in mice whether antigen-encapsulated PLGA (poly-lactic-co-glycolic acid), PLGA-TMC (N-trimethyl chitosan) or TMC-TPP (tri-polyphosphate) nanoparticles can also be used to modulate the immunological outcome after nasal vaccination. These three nanoparticles enhanced the antigen presentation by dendritic cells, as shown by increased in vitro and in vivo CD4+ T-cell proliferation. However, only nasal PLGA nanoparticles were found to induce an immunoregulatory response as shown by enhanced Foxp3 expression in the nasopharynx associated lymphoid tissue and cervical lymph nodes. Nasal administration of OVA-containing PLGA particle resulted in functional suppression of an OVA-specific Th-1 mediated delayed-type hypersensitivity reaction, while TMC-TPP nanoparticles induced humoral immunity, which coincided with the enhanced generation of OVA-specific B-cells in the cervical lymph nodes. Intranasal treatment with Hsp70-mB29a peptide-loaded PLGA nanoparticles suppressed proteoglycan-induced arthritis, leading to a significant reduction of disease. We have uncovered a role for PLGA nanoparticles to enhance CD4+ T-cell mediated immunomodulation after nasal application. The exploitation of this differential regulation of nanoparticles to modulate nasal immune responses can lead to innovative vaccine development for prophylactic or therapeutic vaccination in infectious or autoimmune diseases.
Highlights
Nasal vaccination is described for the prevention of infectious diseases such as hepatitis B [1,2] or influenza [3,4]
Since mucosal antigen application elicits different immune responses such as T-helper 2 (TH2)-mediated humoral immunity or T-helper 1 (TH1)-mediated Delayed-Type Hypersensitivity (DTH) [21,22,23], we explored if nanoparticles can differentially modulate the outcome of nasal vaccination
We treated DCs in vitro with OVA encapsulated in PLGA, PLGA-TMC or TMC-TPP nanoparticles or soluble OVA as a control and studied phenotypic and functional differences between treated DCs
Summary
Nasal vaccination is described for the prevention of infectious diseases such as hepatitis B [1,2] or influenza [3,4]. Since mucosal antigen application elicits different immune responses such as T-helper 2 (TH2)-mediated humoral immunity or T-helper 1 (TH1)-mediated Delayed-Type Hypersensitivity (DTH) [21,22,23], we explored if nanoparticles can differentially modulate the outcome of nasal vaccination. The readout to evaluate the efficacy of the applied vaccine relies mostly on induction of humoral immune responses as indicated by increased antigen-specific antibody titers [4,18,24]. This does not give insight into the underlying immunological mechanisms that drive the response towards sOVA-FITC or OVA-FITC encapsulated into PLGA, PLGA-TMC or TMC-TPP nanoparticles at different concentrations. Little is still known about the role of CD4+ T-cells in nasal vaccination and how different nanoparticle treatment might influence the activation of these cells, locally and in the peripheral tissues
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
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 call
