Novel Biomimetic Reconstituted Built-in Adjuvanted Hepatitis B Vaccine for Transcutaneous Immunization

Transcutaneous immunization is the administration of a vaccine on the skin to generate efficient systemic and mucosal immune responses against an antigen. In the present study, reconstituted hepatitis B surface antigen vesicles (HBsAg-REVs) integrated with monophosphoryl lipid A were prepared by the delipidation-reconstitution method and tested as built-in adjuvanted vaccine, system for transcutaneous immunization using a combined approach of tape strippings, and enhanced antigen skin contact time. Prepared vesicles were extensively characterized for size, shape, zeta potential, and antigen protein loading efficiency. Following topical application, HBsAg-REVs skin permeation on isolated rat skin and cell uptake by bone marrow–derived dendritic cells were determined by confocal laser scanning microscopy and flow cytometry, respectively. The humoral and cellular immune responses elicited by HBsAg-REVs via transcutaneous immunization were comparable to the marketed intramuscular hepatitis B vaccine formulation with predefined immunization protocols. This study supports that delivery of reconstituted HBsAg vesicles via transcutaneous route may open a new vista for designing topical vaccines with possible immune protection against hepatitis B in future.