Viral constructs for use in enhancing t-cell priming during vaccination

Abstract

The invention provides virus-based expression vectors comprising immune-checkpoint inhibitor inserts for use as effective adjuvants in enhancing T-cell priming to an antigen in a host during a vaccination regimen. In particular, the compositions described herein are novel recombinant modified vaccinia Ankara (MVA) viral constructs encoding one or more peptides which, upon administration, are expressed in a multimer conformation and subsequently cleaved and secreted from the cell. Such peptides are capable of downregulating an immune checkpoint pathway, for example, by inhibiting the activation of programmed-cell death protein 1 (PD-1), programed cell death ligand 1 (PD-L1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), or another immune checkpoint regulator, or a combination thereof. When used in concert with the administration of an antigen during a vaccination strategy, the immune checkpoint expressing MVA viral construct provides significantly improved antigen-specific CD8+ T cell expansion, increased antigenic responses, and improved vaccination efficacy.

Dependencies are inferred from the claim text.