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Potent Immune Response against HIV-1 and Protection from Virus Challenge in hu-PBL-SCID Mice Immunized with Inactivated Virus-pulsed Dendritic Cells Generated in the Presence of IFN-

Laboratory of Virology, Istituto Superiore di Sanità, Rome, Italy 00161

Address correspondence to Filippo Belardelli, Laboratory of Virology, Istituto Superiore di Sanità, Viale Regina Elena, 299, Rome, Italy 00161. Phone: 39-06-4990-3290; Fax: 39-06-4990-2097; E-mail: belard{at}iss.it

A major challenge of AIDS research is the development of therapeutic vaccine strategies capable of inducing the humoral and cellular arms of the immune responses against HIV-1. In this work, we evaluated the capability of DCs pulsed with aldrithiol-2–inactivated HIV-1 in inducing a protective antiviral human immune response in SCID mice reconstituted with human PBL (hu-PBL-SCID mice). Immunization of hu-PBL-SCID mice with DCs generated after exposure of monocytes to GM-CSF/IFN- (IFN-DCs) and pulsed with inactivated HIV-1 resulted in a marked induction of human anti–HIV-1 antibodies, which was associated with the detection of anti-HIV neutralizing activity in the serum. This vaccination schedule also promoted the generation of a human CD8⁺ T cell response against HIV-1, as measured by IFN- Elispot analysis. Notably, when the hu-PBL-SCID mice immunized with antigen-pulsed IFN-DCs were infected with HIV-1, inhibition of virus infection was observed as compared with control animals. These results suggest that IFN-DCs pulsed with inactivated HIV-1 can represent a valuable approach of immune intervention in HIV-1–infected patients.

Key Words: antigen presenting cell • vaccine • neutralizing antibodies • CD8⁺ T lymphocytes • AIDS

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