title: A polymer/oil based nanovaccine as a single-dose immunization approach.
abstract: The recognized necessity for new antigen delivery carriers with the capacity to boost, modulate and prolong neutralizing immune responses prompted our approach, in which we describe a multifunctional nanocarrier consisting of an oily nanocontainer protected by a polymeric shell made of chitosan (CS), named CS nanocapsules (CSNC). The CS shell can associate the antigen on its surface, whereas the oily core might provide additional immunostimulating properties. In this first characterization of the system, we intended to study the influence of different antigen organizations on the nanocarrier's surface (using the recombinant hepatitis B surface antigen -rHBsAg- as a model antigen) on their long-term immunopotentiating effect, without any additional immunostimulant. Thus, two prototypes of antigen-loaded CSNC (CSNC+ and CSNC-), exhibiting similar particle size (200 nm) and high antigen association efficiency (>80%), were developed with different surface composition (polymer/antigen ratios) and surface charge (positive/negative, respectively). The biological evaluation of these nanovaccines evidenced the superiority of the CSNC+ as compared to CSNC- and alum-rHBsAg in terms of neutralizing antibody responses, following intramuscular vaccination. Moreover, a single dose of CSNC+ led to similar IgG levels to the positive control. The IgG1/IgG2a ratio suggested a mixed Th1/Th2 response elicited by CSNC+, in contrast to the typical Th2-biased response of alum. Finally, CSNC+ could be freeze-dried without altering its physicochemical properties and adjuvant effect in vivo. In conclusion, the evaluation of CSNC+ confirms its interesting features for enhancing, prolonging and modulating the type of immune response against subunit antigens, such as rHBsAg.
authors.affiliation: Pharmacy and Pharmaceutical Technology Department, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), University of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Vicente
authors.forename: Belen
authors.initials: B
authors.lastname: Diaz-Freitas
authors.forename: Mercedes
authors.initials: M
authors.lastname: Peleteiro
authors.forename: Alejandro
authors.initials: A
authors.lastname: Sanchez
authors.forename: David W
authors.initials: DW
authors.lastname: Pascual
authors.forename: Africa
authors.initials: A
authors.lastname: Gonzalez-Fernandez
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Alonso
mesh_terms: D000818:Animals; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D005612:Freeze Drying; D006511:Hepatitis B Antigens / Q000276:immunology; D007114:Immunization / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D053769:Nanocapsules / Q000737:chemistry*; D009821:Oils / Q000737:chemistry*; D013997:Time Factors; D014612:Vaccines / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D014867:Water / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D006511:Hepatitis B Antigens; D053769:Nanocapsules; D009821:Oils; D014612:Vaccines; D014867:Water; D048271:Chitosan