Compositions are provided comprising a replication-competent herpesvirus vector system and/or a herpesvirus vector particle comprising a heterologous recombinant transgene of interest encoding an antigen of interest (e.g., a tumor-associated antigen, a microbial antigen, etc.), wherein the recombinant transgene has been modified to comprise a codon usage signature of a herpesvirus late gene operably linked to an active promoter. Such compositions find use in a variety of methods including, for example, methods of generating an immune response against an antigen of interest in a subject in need thereof, as well as methods for treating or preventing cancer or a microbial infection.