Quilmes National University

In this project, we develop adjuvant nanovesicles for needle-free vaccination against viral and parasitic diseases.

Needle-free topical vaccination is attractive since it has the potential to make vaccine delivery more equitable, safer and equally or more efficient than parenteral (intramuscular or subcutaneous) vaccination. Major benefits include the possibility of self-administration, improved patient compliance, no requirement of “sharps” waste removal, and reduced storage and transport issues. Topical vaccination however, is challenged by the barrier that the stratum corneum interposed between antigens-adjuvants and the skin-associated lymphoid tissue (SALT) lying few hundred micrometers depth from skin surface. In this scenario, soft matter having elasto-mechanical properties enabling the penetration of the intact stratum corneum, could pave the way towards safer and efficient topical vaccination. We have developed ultradeformable archaeosomes made of sn 2,3 ether linked phytanyl saturated archaeolipids plus surfactants (UDA). The resulting UDA combines a high uptaken by antigen presenting cells and high structural stability because of the presence of archaeolipids with deep skin penetration because to the reduced Young modulus of the bilayers. UDA are efficient carriers for topical delivery of antigens; for instance, UDA can penetrate the stratum corneum to deliver proteins of molecular weight ~45 KDa up to the viable epidermis and induces long lasting antigen-specific serum IgG titers.

From a production point of view, UDA are super-stable nanovesicles: they could resist heat sterilization and storage under cold-free conditions, and no antigen inclusion- only a physical mixture- is sufficient to elicit an antigen-specific systemic immune response.

Currently, we are exploring UDA as adjuvant for topical influenza vaccine. We hope that UDA as ready-to- use topical adjuvant would lead to simpler manufacture processing and cheaper vaccines for large poor populations in sub-tropical and tropical zones.