Heterologous prime-boost is a common vaccination strategy to elicit CD8(+) T cells (T(CD8+)), and vaccinia virus (VACV) has been widely used as a boosting vector. Studies with other viruses have suggested that priming may reduce responses to native epitopes in boosting vectors as well as improve responses to primed epitopes. We explored this possibility with a VACV model in mice and find that irrespective of an epitope's dominance, prior priming was able to double T(CD8+) responses. More surprisingly, and in contrast to findings for other viruses, responses to remaining epitopes were undisturbed, leaving the overall dominance hierarchy unchanged.