Co-delivery of viral proteins and a TLR7 agonist from polysaccharide nanocapsules: A needle-free vaccination strategy

• Published in: Journal of controlled release 2013-12, Vol.172 (3), p.773-781
• Main Authors: Vicente, Sara, Peleteiro, Mercedes, Díaz-Freitas, Belen, Sanchez, Alejandro, González-Fernández, África, Alonso, María J.
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - administration & dosage; Adjuvants, Immunologic - metabolism; agonists; Aminoquinolines - administration & dosage; Aminoquinolines - immunology; Animals; blood serum; Cell Line; cell-mediated immunity; chitosan; Chitosan - chemistry; Co-delivery; complement; Complement Activation; Female; Hepatitis B; Hepatitis B - immunology; Hepatitis B - prevention & control; hepatitis B antigens; Hepatitis B Surface Antigens - administration & dosage; Hepatitis B Surface Antigens - immunology; Hepatitis B virus; humoral immunity; hydrophobicity; Imiquimod; immune response; immunoglobulin G; immunologic memory; immunostimulants; interleukin-6; intranasal administration; macrophages; Macrophages - immunology; Mice; Mice, Inbred BALB C; Mucosal vaccination; Nanocapsules; Nanocapsules - chemistry; nanocarriers; nasal mucosa; secretion; Toll-like receptor 7; Toll-Like Receptor 7 - agonists; tumor necrosis factor-alpha; Vaccination; viral proteins; zeta potential
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2013.09.012

Here we report a new nanotechnology-based nasal vaccination concept intended to elicit both, specific humoral and cellular immune responses. The concept relies on the use of a multifunctional antigen nanocarrier consisting of a hydrophobic nanocore, which can allocate lipophilic immunostimulants, and a polymeric corona made of chitosan (CS), intended to associate antigens and facilitate their transport across the nasal mucosa. The Toll-like receptor 7 (TLR7) agonist, imiquimod, and the recombinant hepatitis B surface antigen (HB), were selected as model molecules for the validation of the concept. The multifunctional nanocarriers had a nanometric size (around 200nm), a high positive zeta potential (+45mV) and a high antigen association efficiency (70%). They also exhibited the ability to enter macrophages in vitro and to effectively deliver the associated imiquimod intracellularly, as noted by the secretion of pro-inflammatory cytokines (i.e. IL-6 and TNF-α). However, the nanocarriers did not induce the in vitro activation of the complement cascade. Finally, the positive effect of the co-delivery of HB and imiquimod from the nanocapsules was evidenced upon intranasal administration to mice. The nanocapsules containing imiquimod elicited a protective immune response characterized by increasing IgG levels over time and specific immunological memory. Additionally, the levels of serum IgG subclasses (IgG1 and IgG2a) indicated a balanced cellular/humoral response, thus suggesting the capacity of the nanocapsules to modulate the systemic immune response upon nasal vaccination. [Display omitted]