Described herein are recombinant rhesus cytomegalovirus (RhCMV) and human cytomegalovirus (HCMV) vectors encoding heterologous antigens, such as pathogen-specific antigens or tumor antigens. The recombinant vectors elicit and maintain high level cellular and humoral immune responses specific for the heterologous antigen. The recombinant RhCMV and HCMV vectors may be used, for example, for the treatment or prevention of infectious disease or cancer. In some examples, the recombinant RhCMV or HCMV vectors may include deletions in genes encoding immunomodulatory proteins. In some examples, the recombinant RhCMV or HCMV vectors may be deficient or impaired in their ability to replicate within a cell, disseminate within the host or spread among hosts by including a deletion in one or more genes essential or augmenting for CMV replication, dissemination or spread.