16th International AIDS Conference Toronto, Canada - August 13 - 18, 2006

CHIMERIC CD40L/SHIV VIRUS-LIKE PARTICLES ENHANCED DENDRITIC CELLS ACTIVATION AND BOOSTED IMMUNE RESPONSES AGAINST HIV

Int Conf AIDS. 2006 Aug 13-18;16 Abstract No. ThAa0105

Zhang R., Li M., Chen C., Yao Q.
Baylor College of Medicine, Houston, United States

BACKGROUND: Dendritic cells (DCs) are potent antigen-presenting cells and can be activated by the interaction between CD40 on DCs and CD40 ligand (CD40L) on T cells. The purpose of this study was to investigate whether chemeric CD40L/SHIV virus-like particles (VLPs) can activate DCs and contribute to the enhanced immune responses to SIV Gag and HIV Env protein in vivo.

METHODS: CD14 positive cells purified from PBMC were differentiated into DCs in the presence of GM-CSF and IL-4 with or without VLPs treatment. DC surface markers, mixed lymphocytes reaction (MLR), cytokines production were determined and compared. C57BL/6J mice were immunized through intradermal route with CD40L/SIV(Gag)VLP, CD40L/SHIV(Gag + Env)VLPs or SHIV(Gag + Env)VLPs. The serum IgG titers to HIV Env and HIV-1 Env. or SIV gag specific IFN-γ or IL-4 producing cells were measured and compared.

RESULTS: CD40L/SHIV VLPs were found to significantly up-regulate DC maturation marker CD83 as well as costimulatory molecules CD40, CD80 and CD86. Upon CD40L/SHIV VLP treatment, there was approximately a 200-fold increase of TNF-α, a 2-fold increase of IFN-γ and a 16-fold increase of IL-12 production. In addition, CD40L/SHIV VLP-treated DCs presented more than a 3-fold increase in allogeneic T cell proliferation. Moreover, mice immunized with CD40L/SHIV VLPs showed more than 2-fold higher HIV Env specific IgG production compare to that in SHIV VLP. A significant enhancement of SIV Gag or HIV Env specific IFN-γ and IL-4 producing cells were detected in CD40L/SHIV(Gag + Env)VLPs immunized mice.

CONCLUSIONS: These data demonstrate that chimeric CD40L/SHIV VLPs are able to potently induce DC maturation and activation, mainly through CD40 and CD40L interaction. CD40L/VLPs can enhance both humoral and cellular immune responses to the SIV Gag and HIV Env protein in a mouse model. The results indicate that incorporation of CD40L into VLPs may be highly effective in enhancing immunogenicity of HIV vaccines.

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2006-08-13
ThAa0105

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