TOPICAL VACCINATION WITH SUPER-STABLE READY TO USE NANOVESICLES

CAIMI, AYELEN T; PARRA, FEDERICO; DE FARIAS, MARCELO A.; PORTUGAL, RODRIGO; PEREZ, ANA P.; ROMERO, EDER L.; MORILLA, MARIA J

Mar del Plata

Congreso; SAIC-SAI-SAFE 2016; 2016

Topical vaccination has the potential to make vaccine delivery more equitable, safer and as efficient than parenteral vaccination. Topical vaccination however, is challenged by the presence of the stratum corneum interposed between antigens/adjuvants and the skin-associated lymphoid tissue. Ultradeformable archaeosomes (UDA), vesicles made of polar archaeolipids (TPA) from the hyperhalophile archaea Halorubrum tebenquichense (mixture of sn 2,3 ether linked saturated archaeolipids) plus sodium cholate, that can penetrate the intact stratum corneum, could pave the way to an efficient topical vaccination. In this work we submitted UDA to heat stress of sterilization and to lyophilisation. Then we screened the immunogenicity of the model antigen ovalbumin (OVA) associated to UDA in different ways (suspended in the aqueous space, adsorbed to the surface and administered separated) upon topically applied to Balb-c mice; and the adjuvant properties of sterilized and lyophilized UDA was determined. Results showed that after autoclaving the population size and polydispersity index (PDI) of UDA were conserved; in contrast, UDL increased its size by 5 folds. Lyophilized UDA with optimum lyoprotectant combination (0.068 % w/v glucose -2.5 % v/v glycerol), conserved the size and PDI after 4 months at 40°C; in contrast, UDL increased by 8 folds the size. Surprising we found that topical administration of UDA with antigen encapsulated in the aqueous space or adsorbed to the surface elicited the same immune response. Finally, we showed that sterilized and lyophilized UDA retain adjuvant activity upon mixing with antigen. In conclusion, the presence of TPA in UDA provides the colloidal stability needed to be autoclaved, lyophilized and storage under cold-free conditions (super-stable). Furthermore, UDA have the potential to function as an adjuvant when mixed with antigen solutions that does not require the complex steps of antigen loading (ready to use).