|
|
Dendritic Cells Infected with Recombinant Canarypox Virus Induce Potent Anti-HIV Cytolytic and Helper T Cell Responses from Chronically Infected Individuals M. LARSSON*1, J. ENGELMAYER1, M. LEE1, W. COX2, R. STEINMAN1, and N. BHARDWAJ1. 1The Rockfeller Univ., New York, NY; and 2Virogenetics Corp., Troy, NY Recombinant canarypox virus vectors containing HIV-1 sequences are promising vaccine candidates, as they do not replicate in human cells and have a record of safety in humans. The vaccines have, however, only induced weak and in some cases transient antigen specific CTL responses in clinical studies of volunteers. An attractive way to enhance these responses would be to target canarypox virus to potent antigen presenting cells, e.g. dendritic cells (DCs). We have studied (A) the interaction between canarypox virus and DCs and (B) the T cell response induced by DCs infected with canarypox virus vectors expressing HIV-1 genes. Despite the relative low frequency of DCs infected with canarypox virus, the DCs induced strong CTL responses such as cytolysis, secretion of IFN-g and b-chemokines. Furthermore, the responses induced by canarypox virus infected DCs were at least as potent as the ones induced by vaccinia virus infected or peptide pulsed cells. Addition of exogenous cytokines was not necessary to elicit the CTLs but the presence of CD4 T cells was required. Canarypox virus infected DCs were also able to stimulate HIV specific CD4 helper responses needed to maintain effective CTL responses. Therefore, targeting canarypox virus vectors to DCs could efficiently enhance anti-HIV CTL responses in vivo. Key Words: canarypox vectors, dendritic cells, T cell responses |
|
© 7th
Conference on Retroviruses and Opportunistic Infections, |