title: Topical vaccination with super-stable ready to use nanovesicles.
abstract: Ultradeformable archaeosomes (UDA) are nanovesicles made of total polar archaeolipids (TPA) from the archaea Halorubrum tebenquichense, soybean phosphatidylcholine and sodium cholate (3:3:1w/w). Fresh dispersions of UDA including different type of antigens are acknowledged as efficient topical vaccination agents. UDA dispersions however, if manufactured for pharmaceutical use, have to maintain colloidal stability upon liposomicidal processes such as sterilization and lyophilization (SLRUDA), needed to extend shelf life during storage. The remaining capacity ofSLRUDA to act as adjuvants was therefore tested here for the first time. Another unexplored issue addressed here, is the outcome of replacing classical antigen inclusion into nanovesicles by their physical mixture. Our results showed that UDA behaved as super-stable nanovesicles because of its high endurance during heat sterilization and storage for 5 months at 40°C. The archaeolipid content of UDA however, was insufficient to protect it against lyophilization, which demanded the addition of 2.5% v/v glycerol plus 0.07% w/v glucose. No significant differences were found between serum anti-ovalbumin (OVA) IgG titers induced by fresh orSLRUDA upon topical application of 4 weekly doses at 600μg lipids/75μg OVA to Balb/c mice. Finally,SLRUDA mixed with OVA elicited the same Th2 biased plus a non-specific cell mediated response than OVA encapsulated within UDA. Concluding, we showed that TPA is key component of super-stable nanovesicles that confers resistance to heat sterilization and to storage under cold-free conditions. The finding ofSLRUDA as ready-to-use topical adjuvant would lead to simpler manufacture processing and cheaper products. .
authors.affiliation: Nanomedicine Research Program, Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, Roque Saenz Peña 352, Bernal, B1876BXD, Argentina.
authors.forename: Ayelen Tatiana
authors.initials: AT
authors.lastname: Caimi
authors.affiliation: Nanomedicine Research Program, Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, Roque Saenz Peña 352, Bernal, B1876BXD, Argentina.
authors.forename: Federico
authors.initials: F
authors.lastname: Parra
authors.affiliation: Brazilian Nanotechnology National Laboratory, CNPEM, Caixa Postal 6192, CEP 13.083-970, Campinas, São Paulo, Brazil.
authors.forename: Marcelo Alexandre
authors.initials: MA
authors.lastname: de Farias
authors.affiliation: Brazilian Nanotechnology National Laboratory, CNPEM, Caixa Postal 6192, CEP 13.083-970, Campinas, São Paulo, Brazil.
authors.forename: Rodrigo Villares
authors.initials: RV
authors.lastname: Portugal
authors.affiliation: Nanomedicine Research Program, Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, Roque Saenz Peña 352, Bernal, B1876BXD, Argentina.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Perez
authors.affiliation: Nanomedicine Research Program, Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, Roque Saenz Peña 352, Bernal, B1876BXD, Argentina.
authors.forename: Eder Lilia
authors.initials: EL
authors.lastname: Romero
authors.affiliation: Nanomedicine Research Program, Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, Roque Saenz Peña 352, Bernal, B1876BXD, Argentina. Electronic address: jmorilla@unq.edu.ar.
authors.forename: Maria Jose
authors.initials: MJ
authors.lastname: Morilla
mesh_terms: D005612:Freeze Drying; D005995:Glyceryl Ethers / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry*; D013242:Sterilization; D014611:Vaccination
chemical_list: D005995:Glyceryl Ethers; C094417:archaeol lipid
keywords: Archaeolipids; Cold-free storage; Lyophilization; Sterilization