A REPLICATION-DEFECTIVE ALPHAVIRUS VACCINE LINKING ANTIGEN WITH AN IMMUNOGENICITY-POTENTIATING POLYPEPTIDE AND A METHOD OF DELIVERY THE SAME

摘要

Superior molecular vaccines comprise nucleic acids in the form of PCL-generated replication-defective alphavirus replicons, preferably Sindbis virus, that encode a fusion polypeptide that includes an antigenic peptide or polypeptide against which an immune response is desired. Fused to the antigenic peptide is at least a second polypeptide that is an immunogenicity-potentiating olypeptide acting by any of a number of mechanisms to promote immunogenicity of the antigen. Examples include intercellular spreading proteins, in particular a herpes virus protein VP22 or a homologue or functional derivative thereof. Other examples are proteins that stimulate MHC class I processing of the antigen, target the antigen to APCs promote development and growth of immature DCs or stimulate DC antigen presenting activity. The nucleic acid can encode any antigenic epitope of interest, preferably an epitope that is processed and presented by MHC class I proteins. Antigens of pathogenic organisms and cells such as tumor cells are preferred. Vaccines comprising HPV-16 E7 oncoprotein are exemplified. Also disclosed are methods of using the vaccines to induce heightened T cell mediated immunity, in particular by cytotoxic T lymphocytes, leading to protection from or treatment of a tumor.