Mature Dendritic Cells Infected with Canarypox Virus Elicit Strong Anti-Human Immunodeficiency Virus CD8+and CD4+ T-Cell Responses from Chronically Infected …

J Engelmayer, M Larsson, A Lee, M Lee… - Journal of …, 2001 - Am Soc Microbiol
J Engelmayer, M Larsson, A Lee, M Lee, WI Cox, RM Steinman, N Bhardwaj
Journal of virology, 2001Am Soc Microbiol
Recombinant canarypox virus vectors containing human immunodeficiency virus type 1 (HIV-
1) sequences are promising vaccine candidates, as they replicate poorly in human cells.
However, when delivered intramuscularly the vaccines 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 professional antigen-presenting cells such as dendritic cells (DCs). We studied (i) …
Abstract
Recombinant canarypox virus vectors containing human immunodeficiency virus type 1 (HIV-1) sequences are promising vaccine candidates, as they replicate poorly in human cells. However, when delivered intramuscularly the vaccines 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 professional antigen-presenting cells such as dendritic cells (DCs). We studied (i) the interaction between canarypox virus and DCs and (ii) the T-cell responses induced by DCs infected with canarypox virus vectors containing HIV-1 genes. Mature and not immature DCs resisted the cytopathic effects of canarypox virus and elicited strong effector CD8+ T-cell responses from chronically infected HIV+ individuals, e.g., cytolysis, and secretion of gamma interferon (IFN-γ) and β-chemokines. Furthermore, canarypox virus-infected DCs were >30-fold more efficient than monocytes and induced responses that were comparable to those induced by vaccinia virus vectors or peptides. Addition of exogenous cytokines was not necessary to elicit CD8+ effector cells, although the presence of CD4+ T cells was required for their expansion and maintenance. Most strikingly, canarypox virus-infected DCs were directly able to stimulate HIV-specific, IFN-γ-secreting CD4 helper responses from bulk as well as purified CD4+ T cells. Therefore, these results suggest that targeting canarypox virus vectors to mature DCs could potentially elicit both anti-HIV CD8+and CD4+ helper responses in vivo.
American Society for Microbiology