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-alpha.
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-alpha (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-gamma 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.
Lapenta
Caterina
C
Laboratory of Virology, Istituto Superiore di Sanità, Viale Regina Elena, 299, Rome, Italy 00161.
Santini
Stefano M
SM
Logozzi
Mariantonia
M
Spada
Massimo
M
Andreotti
Mauro
M
Di Pucchio
Tiziana
T
Parlato
Stefania
S
Belardelli
Filippo
F
D016915:AIDS Vaccines / Q000627:therapeutic use*; D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000517:prevention & control; D000818:Animals; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D018189:Immunomagnetic Separation / Q000379:methods; D016898:Interferon-alpha / Q000276:immunology*; D017710:Lymphocyte Transfusion; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology*; D051379:Mice; D016513:Mice, SCID; D014183:Transplantation, Heterologous / Q000276:immunology; D015164:Vaccines, Inactivated / Q000627:therapeutic use*
D016915:AIDS Vaccines; D016898:Interferon-alpha; D015164:Vaccines, Inactivated