Topical vaccination with super-stable ready to use nanovesicles

CAIMI AT; PARRA F; DE FARIAS MA; PORTUGAL RV; PEREZ AP; ROMERO EL; MORILLA MJ

Congreso; Reunión conjunta 2016 SAIC-SAI-SAFE-AACyTAL-NANOMEDar; 2016

Topical vaccination has the potential to make vaccine deliverymore equitable, safer and as efficient as parenteral vaccination.Topical vaccination however, is challenged by the presence of thestratum corneum interposed between antigens/adjuvants and theskin-associated lymphoid tissue. Ultradeformable archaeosomes(UDA), vesicles made of polar archaeolipids (TPA) from the hyperhalophilearchaea Halorubrum tebenquichense (mixture of sn 2,3ether linked saturated archaeolipids) plus sodium cholate, that canpenetrate the intact stratum corneum, could pave the way for anefficient topical vaccination. In this work we submitted UDA to heatstress of sterilization and to lyophilisation. Then we screened theimmunogenicity of the model antigen ovalbumin (OVA) associatedto UDA in different ways (suspended in the aqueous space, adsorbedto the surface and administered separated) upon topicallyapplied to Balb-c mice; and the adjuvant properties of sterilizedand lyophilized UDA was determined. Results showed that afterautoclaving the population size and polydispersity index (PDI) ofUDA were conserved; in contrast, UDL increased its size by 5folds. Lyophilized UDA with optimum lyoprotectant combination(0.068% w/v glucose -2.5% v/v glycerol), conserved the size andPDI after 4 months at 40°C; in contrast, UDL increased by 8 foldsthe size. Surprisingly we found that topical administration of UDAwith antigen encapsulated in the aqueous space or adsorbed to thesurface elicited the same immune response. Finally, we showedthat sterilized and lyophilized UDA retain adjuvant activity uponmixing with antigen. In conclusion, the presence of TPA in UDAprovides the colloidal stability needed to be autoclaved, lyophilizedand stored under cold-free conditions (super-stable). Furthermore,UDA have the potential to function as an adjuvant when mixedwith antigen solutions that does not require the complex steps ofantigen loading (ready to use).