Heterologous Booster Immunizations Alphavirus Replicons and Homologous or Cell Responses after Priming with T + Kinetic and Phenotypic Analysis of CD 8

Alphavirus replicons are potent inducers of CD8 T cell responses and thus constitute an attractive vaccine vector platform for developing novel vaccines. However, the kinetics and memory phenotype of CD8 T cell responses induced by alphavirus replicons are not well characterized. Furthermore, little is known how priming with alphavirus replicons affects booster immune responses induced by other vaccine modalities. We demonstrate here that a single immunization with an alphavirus replicon, administered as viral particles or naked DNA, induced an antigen-specific CD8 T cell response that had a sharp peak, followed by a rapid contraction. Administering a homologous boost before contraction had occurred did not further increase the response. In contrast, boosting after contraction when CD8 T cells had obtained a memory phenotype (based on CD127/CD62L expression), resulted in maintenance of CD8 T cells with a high recall capacity (based on CD27/CD43 expression). Increasing the dose of replicon particles promoted T effector memory (Tem) and inhibited T central memory development. Moreover, infection with a replicating alphavirus induced a similar distribution of CD8 T cells as the replicon vector. Lastly, the distribution of T cell subpopulations induced by a DNA-launched alphavirus replicon could be altered by heterologous boosts. For instance, boosting with a poxvirus vector (MVA) favored expansion of the Tem compartment. In summary, we have characterized the antigen-specific CD8 T cell response induced by alphavirus replicon vectors and demonstrated how it can be altered by homologous and heterologous boost immunizations.