(600d) Vaccination Using Topical Formulations

The human skin is an immunologically active site comprising of keratinocytes, Langerhans cells and mast cells that form a part of an immune network. The high accessibility of skin along with its inherent immunological capabilities makes it an excellent portal for vaccine delivery. Application of a vaccine on intact skin through an ointment or a patch provides several advantages over needles in terms of safety, compliance and ease of use.

Skin, however, has evolved to impede the flux of foreign molecules, such as toxics and xenobiotics, across it. Delivery of large molecules such as antigens across the skin (typically 10-100 kDa) is extremely difficult. Even if small amounts of antigens were to penetrate into the skin, they may not necessarily generate a sufficiently strong immune response in the absence of an adjuvant. Accordingly, a topical formulation for vaccination must comprise agents that are capable of enhancing skin permeability to vaccines and also act as strong adjuvants. A single chemical is unlikely to perform such a complex task and hence mixtures of chemicals must be identified for this purpose. Here, we describe a method of identification of such mixtures and report on their effectiveness in performing vaccination in mice.

We chose 28 distinct chemicals from a wide spectrum of chemical functionalities such as surfactants (anionic, cationic, non-ionic and zwitterionic), fatty acids, esters and analogues of Azone. These chemicals were randomly combined in pairs of three at multiple concentrations and compositions resulting in over 500 distinct formulations. The potential of the formulations in increasing transport across the skin was assessed in porcine skin using a high throughput screening method (INSIGHT). The ability of selected formulations to stimulate the immune component of the skin was tested using an in vitro reconstituted skin model. Leading formulations from these screenings were tested for their ability to deliver a model vaccine (ovalbumin) in mice. The leading formulations generated a strong IgG titer against ovalbumin in mice after one boosting. These results open up the possibility of developing a simple, ointment or a patch-like vaccine.