Co-delivery of viral proteins and a TLR7 agonist from polysaccharide nanocapsules: a needle-free vaccination strategy.
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 200 nm), a high positive zeta potential (+45 mV) 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.
Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), University of Santiago de Compostela, 15706 Campus Vida, Santiago de Compostela, Spain; Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Santiago de Compostela, 15705 Campus Vida, Santiago de Compostela, Spain.
Sara
S
Vicente
Mercedes
M
Peleteiro
Belen
B
Díaz-Freitas
Alejandro
A
Sanchez
África
Á
González-Fernández
María J
MJ
Alonso
D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000378:metabolism; D000634:Aminoquinolines / Q000008:administration & dosage* / Q000276:immunology; D000818:Animals; D002460:Cell Line; D048271:Chitosan / Q000737:chemistry; D003167:Complement Activation; D005260:Female; D006509:Hepatitis B / Q000276:immunology / Q000517:prevention & control; D006514:Hepatitis B Surface Antigens / Q000008:administration & dosage* / Q000276:immunology; D000077271:Imiquimod; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D053769:Nanocapsules / Q000737:chemistry*; D051199:Toll-Like Receptor 7 / Q000819:agonists*; D014611:Vaccination
D000276:Adjuvants, Immunologic; D000634:Aminoquinolines; D006514:Hepatitis B Surface Antigens; D053769:Nanocapsules; D051199:Toll-Like Receptor 7; D048271:Chitosan; D000077271:Imiquimod
Co-delivery; Hepatitis B; Imiquimod; Mucosal vaccination; Nanocapsules