Mature dendritic cells infected with canarypox virus elicit strong anti-human immunodeficiency virus CD8(+) and CD4(+) T-cell responses from chronically infected individuals

Recombinant canarypox virus vectors containing human immunodeficiency virus type 1 (HIV-1) sequences are promising vaccine candidates, as they replica te poorly in human cells. However, when delivered intramuscularly the vacci nes have induced inconsistent and in some cases transient antigen-specific cytotoxic T-cell (CTL) responses in seronegative volunteers. An attractive way to enhance these responses would be to target canarypox virus to profes sional antigen-presenting cells such as dendritic cells (DCs), We studied ( i) the interaction between canarypox virus and DCs and (ii) the T-cell resp onses induced by DCs infected with canarypox virus vectors containing HIV-1 genes. Mature and not immature DCs resisted the cytopathic effects of cana rypox virus and elicited strong effector CD8(+) T-cell responses from chron ically infected HIV+ individuals, e.g., cytolysis, and secretion of gamma i nterferon (IFN-gamma) and beta -chemokines, Furthermore, canarypox virus-in fected DCs were >30-fold more efficient than monocytes and induced response s that were comparable to those induced by vaccinia virus vectors or peptid es, Addition of exogenous cytokines was not necessary to elicit CD8(+) effe ctor cells, although the presence of CD4(+) T cells was required for their expansion and maintenance. Most strikingly, canarypox virus-infected DCs we re directly able to stimulate HN-specific, IFN-gamma -secreting CD4 helper responses from bulk as well as purified CD4(+) T cells. Therefore, these re sults suggest that targeting canarypox virus vectors to mature DCs could po tentially elicit both anti-HIV CD8(+) and CD4(+) helper responses in vivo.