Influence of adenovirus and MVA vaccines on the breadth and hierarchy of T cell responses

•Viral-vectored vaccines are expected to induce T-cell responses to sub-dominant epitopes.•Hierarchy of T-cell response is influenced by the timing of analysis after a single immunization.•Repeated homologous immunization reduces the breadth of T-cell response.•Heterologous prime-boost induces a modest increase of the subdominant responses.Viral-vectored vaccines are in clinical development for several infectious diseases where T-cell responses can mediate protection, and responses to sub-dominant epitopes is needed. Little is known about the influence of MVA or adenoviral vectors on the hierarchy of the dominant and sub-dominant T-cell epitopes. We investigated this aspect in mice using a malaria immunogen. Our results demonstrate that the T-cell hierarchy is influenced by the timing of analysis, rather than by the vector after a single immunization, with hierarchy changing over time. Repeated homologous immunization reduced the breadth of responses, while heterologous prime-boost induced the strongest response to the dominant epitope, albeit with only modest response to the sub-dominant epitopes