Background Poly( l -lactide) (PLLA) is a biodegradable polymer currently used in many biomedical applications, including the production of resorbable surgical devices, porous scaffolds for tissue engineering, nanoparticles and microparticles for the controlled release of drugs or antigens. The surfaces of lamellar PLLA single crystals (PLLA sc ) were provided with amino groups by reaction with a multifunctional amine and used to adsorb an Escherichia coli -produced human papillomavirus (HPV)16-E7 protein to evaluate its possible use in antigen delivery for vaccine development. Methods PLLA single crystals were made to react with tetraethylenepentamine to obtain amino-functionalized PLLA single crystals (APLLA sc ). Pristine and amino-functionalized PLLA sc showed a two-dimensional microsized and one-dimensional nanosized lamellar morphology, with a lateral dimension of about 15–20 μm, a thickness of about 12 nm, and a surface specific area of about 130 m 2 /g. Both particles were characterized and loaded with HPV16-E7 before being administered to C57BL/6 mice for immunogenicity studies. The E7-specific humoral-mediated and cell-mediated immune response as well as tumor protective immunity were analyzed in mice challenged with TC-1 cancer cells. Results Pristine and amino-functionalized PLLA sc adsorbed similar amounts of E7 protein, but in protein-release experiments E7-PLLA sc released a higher amount of protein than E7-APLLA sc . When the complexes were dried for observation by scanning electron microscopy, both samples showed a compact layer, but E7-APLLA sc showed greater roughness than E7-PLLA sc . Immunization experiments in mice showed that E7-APLLA sc induced a stronger E7-specific immune response when compared with E7-PLLA sc . Immunoglobulin G isotyping and interferon gamma analysis suggested a mixed Th1/Th2 immune response in both E7-PLLA sc -immunized and E7-APLLA sc -immunized mice. However, only the mice receiving E7-APLLA sc were fully protected from TC-1 tumor growth after three doses of vaccine. Conclusion Our results show that APLLA single crystals improve the immunogenicity of HPV16-E7 and indicate that E7-APLLA sc could be used for development of an HPV16 therapeutic vaccine against HPV16-related tumors.

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