Dendritic cell-based vaccine strategy against human immunodeficiency virus clade C: skewing the immune response toward a helper T cell type 2 profile.

Given the continued spread of human immunodeficiency virus (HIV)-1 worldwide, developing efficient vaccine strategies against HIV-1 is a key task. We tested the safety and immunogenicity of a multicomponent, cell-based vaccine that consisted of antigen-expressing apoptotic bodies with or without autologous dendritic cells (DCs). The vaccine strategy involved transfection of human 293T cells with codon-optimized DNA vectors expressing env of HIV1084i, a newly transmitted pediatric HIV-1 clade C strain; SHIV89.6P tat; and SIVmac239 gag-protease. Apoptotic bodies were generated by heat shock and ultraviolet irradiation and mixed either with mouse DCs (DC-cell vaccine) or given directly (cell-only vaccine) to BALB/c mice for initial priming; boosts consisted of apoptotic bodies only. The immunogens were well tolerated with or without DCs. Compared with the cell-only vaccine, the DC-cell vaccine induced higher antibody titers against all three antigens, whereas virus-specific cytotoxic T lymphocyte responses were equally strong in both groups. Iso-type analysis of viral antigen-specific antibodies revealed a skewing toward helper T type 2 responses induced by the DC-cell vaccine but not by the cell-only vaccine. In summary, both vaccine strategies were safe and induced cellular as well as humoral antiviral immunity; the DC-based approach had the advantage of significantly stronger antibody responses.

Functional aspects of binding of monoclonal antibody DCN46 to DC-SIGN on dendritic cells.

Dendritic cell (DC)-specific ICAM-3 grabbing nonintegrin (DC-SIGN) is a DC-specific antigen that plays an important role in the induction of primary immune responses as well as during HIV infection. In the present study, we analyzed the effect of binding of monoclonal antibody DCN46 to DC surface, expressed DC-SIGN on DC function. DC-SIGN antibody treated, immature DC were able to differentiate into mature DC and had the same capacity as untreated DC to induce primary and secondary immune responses. In combination with flow cytometric cell sorting, DC-SIGN antibody treatment of DC yielded highly pure and functional DC. Given the apparent lack of functional effect of monoclonal antibody DCN46 on DC, the latter antibody may prove useful for research on and clinical use of highly pure and functional DC.