Cd40 Ligand-Expressing Recombinant Vaccinia Virus Promotes The Generation Of Cd8(+) Central Memory Tcells

Central memory CD8(+) Tcells (T-CM) play key roles in the protective immunity against infectious agents, cancer immunotherapy, and adoptive treatments of malignant and viral diseases. CD8(+) T-CM cells are characterized by specific phenotypes, homing, and proliferative capacities. However, CD8(+) T-CM-cell generation is challenging, and usually requires CD4(+) CD40L(+) T-cell help during the priming of naive CD8(+) Tcells. We have generated a replication incompetent CD40 ligand-expressing recombinant vaccinia virus (rVV40L) to promote the differentiation of human naive CD8(+) Tcells into T-CM specific for viral and tumor-associated antigens. Soluble CD40 ligand recombinant protein (sCD40L), and vaccinia virus wild-type (VV WT), alone or in combination, were used as controls. Here, we show that, in the absence of CD4(+) Tcells, a single in vitro stimulation of naive CD8(+) Tcells by rVV40L-infected nonprofessional CD14(+) antigen presenting cells promotes the rapid generation of viral or tumor associated antigen-specific CD8(+) Tcells displaying T-CM phenotypic and functional properties. These observations demonstrate the high ability of rVV40L to fine tune CD8(+) mediated immune responses, and strongly support the use of similar reagents for clinical immunization and adoptive immunotherapy purposes.