Superior molecular vaccine based on self-replicating rna, suicidal dna or naked dna vector, that links antigen with polypeptide that promotes antigen presentation

Abstract

Improved molecular vaccines comprise nucleic acid vectors that encode a fusion polypeptide that includes polypeptide or peptide physically linked to an antigen. The linked polypeptide is one that (a) promotes processing of the expressed fusion polypeptide via the MHC class I pathway and/or (b) promotes development or activity of antigen presenting cells, primarily dendritic cells. These vaccines employ one of several types of nucleic acid vectors, each with its own relative advantages: naked DNA plasmids, self-replicating RNA replicons and suicidal DNA-based on viral RNA replicons. Administration of such a vaccine results in enhance immune responses, primarily those mediated by CD8+ cytotoxic T lymphocytes, directed against the immunizing antigen part of the fusion polypeptide. Such vaccines are useful against tumor antigens, viral antigens and antigens of other pathogenic microorganisms and can be used in the prevention or treatment of diseases that include cancer and infections.